08 November 2021

EMA/CHMP/625918/2021
Human Medicines Division

Committee for medicinal products for human use (CHMP)

Draft agenda for the meeting on 08-11 November 2021
Chair: Harald Enzmann – Vice-Chair: Bruno Sepodes

08 November 2021, 09:00 – 19:30, virtual meeting/ room 1C

09 November 2021, 08:30 – 19:30, virtual meeting/ room 1C

10 November 2021, 08:30 – 19:30, virtual meeting/ room 1C

11 November 2021, 08:30 – 17:00, virtual meeting/ room 1C

Disclaimers

Some of the information contained in this agenda is considered commercially confidential or sensitive
and therefore not disclosed. With regard to intended therapeutic indications or procedure scopes listed
against products, it must be noted that these may not reflect the full wording proposed by applicants
and may also vary during the course of the review. Additional details on some of these procedures will
be published in the CHMP meeting highlights once the procedures are finalised and start of referrals
will also be available.

Of note, this agenda is a working document primarily designed for CHMP members and the work the
Committee undertakes.

Note on access to documents

Some documents mentioned in the agenda cannot be released at present following a request for
access to documents within the framework of Regulation (EC) No 1049/2001 as they are subject to on-
going procedures for which a final decision has not yet been adopted. They will become public when
adopted or considered public according to the principles stated in the Agency policy on access to
documents (EMA/127362/2006).

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© European Medicines Agency, 2021. Reproduction is authorised provided the source is acknowledged.
 Table of contents

1. Introduction 8
1.1. Welcome and declarations of interest of members, alternates and experts ............ 8

1.2. Adoption of agenda ................................................................................................ 8

1.3. Adoption of the minutes ......................................................................................... 8

2. Oral Explanations 8
2.1. Pre-authorisation procedure oral explanations....................................................... 8

2.1.1. aducanumab - EMEA/H/C/005558 ................................................................................ 8

2.1.2. tepotinib - EMEA/H/C/005524 ..................................................................................... 8

2.1.3. inebilizumab - Orphan - EMEA/H/C/005818................................................................... 9

2.1.4. casirivimab / imdevimab - EMEA/H/C/005814 ............................................................... 9

2.2. Re-examination procedure oral explanations ......................................................... 9

2.2.1. Nouryant - istradefylline - EMEA/H/C/005308 ................................................................ 9

2.2.2. Nexviadyme - avalglucosidase alfa - Orphan - EMEA/H/C/005501 .................................... 9

2.3. Post-authorisation procedure oral explanations ................................................... 10

2.3.1. Ferriprox - deferiprone - EMEA/H/C/000236/X/0145 .................................................... 10

2.4. Referral procedure oral explanations ................................................................... 10

3. Initial applications 10
3.1. Initial applications; Opinions ................................................................................ 10

3.1.1. bevacizumab - EMEA/H/C/005433 ............................................................................. 10

3.1.2. finerenone - EMEA/H/C/005200 ................................................................................. 10

3.1.3. sotorasib - EMEA/H/C/005522 ................................................................................... 11

3.1.4. regdanvimab - EMEA/H/C/005854 ............................................................................. 11

3.1.5. formoterol fumarate dihydrate / glycopyrronium / budesonide - EMEA/H/C/005311 ......... 11

3.1.6. avacopan - Orphan - EMEA/H/C/005523 ..................................................................... 11

3.1.7. tecovirimat - EMEA/H/C/005248 ................................................................................ 11

3.1.8. glucarpidase - Orphan - EMEA/H/C/005467 ................................................................ 11

3.1.9. eptinezumab - EMEA/H/C/005287.............................................................................. 12

3.1.10. semaglutide - EMEA/H/C/005422............................................................................... 12

3.2. Initial applications; List of outstanding issues (Day 180; Day 120 for procedures with
accelerated assessment timetable) ...................................................................... 12

3.2.1. pneumococcal polysaccharide conjugate vaccine (20-valent, adsorbed) - EMEA/H/C/00545112

3.2.2. dengue tetravalent vaccine (live, attenuated) - Article 58 - EMEA/H/W/005362 ............... 12

3.2.3. betulae cortex dry extract (5-10: 1); extraction solvent: n-heptane 95% (w/w) - Orphan -
EMEA/H/C/005035 ................................................................................................... 13

3.2.4. lonapegsomatropin - Orphan - EMEA/H/C/005367 ....................................................... 13

3.2.5. somatrogon - Orphan - EMEA/H/C/005633 ................................................................. 13

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3.2.6. dengue tetravalent vaccine (live, attenuated) - EMEA/H/C/005155 ................................ 13

3.2.7. pegfilgrastim - EMEA/H/C/004780 ............................................................................. 13

3.2.8. eladocagene exuparvovec - Orphan - ATMP - EMEA/H/C/005352 ................................... 14

3.2.9. linzagolix choline - EMEA/H/C/005442 ........................................................................ 14

3.2.10. rimegepant - EMEA/H/C/005725 ................................................................................ 14

3.3. Initial applications; List of questions (Day 120; Day 90 for procedures with
accelerated assessment timetable) ...................................................................... 14

3.3.1. insulin human - Article 58 - EMEA/H/W/005779........................................................... 14

3.3.2. asciminib - Orphan - EMEA/H/C/005605 ..................................................................... 14

3.3.3. mobocertinib - EMEA/H/C/005621 ............................................................................. 15

3.3.4. eptacog alfa (activated) - EMEA/H/C/005547 .............................................................. 15

3.3.5. insulin human - Article 58 - EMEA/H/W/005780........................................................... 15

3.3.6. tebentafusp - Orphan - EMEA/H/C/004929 ................................................................. 15

3.3.7. voclosporin - EMEA/H/C/005256 ................................................................................ 15

3.3.8. mitapivat - Orphan - EMEA/H/C/005540 ..................................................................... 15

3.3.9. ranibizumab - EMEA/H/C/005019 .............................................................................. 16

3.3.10. valoctocogene roxaparvovec - Orphan - ATMP - EMEA/H/C/005830 ............................... 16

3.3.11. surufatinib - EMEA/H/C/005728 ................................................................................. 16

3.3.12. sorafenib - EMEA/H/C/005921 ................................................................................... 16

3.4. Update on on-going initial applications for Centralised procedure........................ 16

3.4.1. sodium thiosulfate - PUMA - EMEA/H/C/005130 ........................................................... 16

3.4.2. melphalan flufenamide - Orphan - EMEA/H/C/005681 .................................................. 17

3.4.3. lenadogene nolparvovec - Orphan - ATMP - EMEA/H/C/005047 ..................................... 17

3.5. Re-examination of initial application procedures under Article 9(2) of Regulation no

726/2004 ............................................................................................................. 17

3.5.1. Nouryant - istradefylline - EMEA/H/C/005308 .............................................................. 17

3.5.2. Nexviadyme - avalglucosidase alfa - Orphan - EMEA/H/C/005501 .................................. 17

3.6. Initial applications in the decision-making phase ................................................. 18

3.7. Withdrawals of initial marketing authorisation application .................................. 18

4. Extension of marketing authorisation according to Annex I of

Commission Regulation (EC) No 1234/2008 18
4.1. Extension of marketing authorisation according to Annex I of Commission Regulation
(EC) No 1234/2008; Opinion ................................................................................ 18

4.1.1. Adynovi - rurioctocog alfa pegol - EMEA/H/C/004195/X/0018 ....................................... 18

4.1.2. Dupixent - dupilumab - EMEA/H/C/004390/X/0045/G .................................................. 18

4.1.3. Epclusa - sofosbuvir / velpatasvir - EMEA/H/C/004210/X/0056/G .................................. 19

4.1.4. Ferriprox - deferiprone - EMEA/H/C/000236/X/0145 .................................................... 19

4.1.5. Kaftrio - ivacaftor / tezacaftor / elexacaftor - Orphan - EMEA/H/C/005269/X/0008/G ....... 19

4.1.6. Noxafil - posaconazole - EMEA/H/C/000610/X/0063/G ................................................. 19

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4.1.7. Nuwiq - simoctocog alfa - EMEA/H/C/002813/X/0042 .................................................. 20

4.1.8. Ozempic - semaglutide - EMEA/H/C/004174/X/0021 .................................................... 20

4.2. Extension of marketing authorisation according to Annex I of Commission Regulation

(EC) No 1234/2008; Day 180 list of outstanding issues ....................................... 20

4.2.1. Ayvakyt - avapritinib - Orphan - EMEA/H/C/005208/X/0004/G ...................................... 20

4.3. Extension of marketing authorisation according to Annex I of Commission Regulation

(EC) No 1234/2008; Day 120 List of question ...................................................... 21

4.3.1. Genvoya - elvitegravir / cobicistat / emtricitabine / tenofovir alafenamide -

EMEA/H/C/004042/X/0079/G .................................................................................... 21

4.3.2. Ilumetri - tildrakizumab - EMEA/H/C/004514/X/0023 ................................................... 21

4.3.3. Procysbi - mercaptamine - Orphan - EMEA/H/C/002465/X/0035 .................................... 21

4.4. Update on on-going extension application according to Annex I of Commission

Regulation (EC) No 1234/2008 ............................................................................ 22

4.5. Re-examination procedure of extension of marketing authorisation according to

Annex I of Commission Regulation (EC) No 1234/2008 ....................................... 22

5. Type II variations - variation of therapeutic indication procedure

according to Annex I of Commission Regulation (EC) No 1234/2008
22
5.1. Type II variations - variation of therapeutic indication procedure according to
Commission Regulation (EC) No 1234/2008; Opinions or Requests for supplementary
information ........................................................................................................... 22

5.1.1. Beovu - brolucizumab - EMEA/H/C/004913/II/0010 ..................................................... 22

5.1.2. Briviact - brivaracetam - EMEA/H/C/003898/II/0032/G ................................................ 22

5.1.3. Bydureon - exenatide - EMEA/H/C/002020/II/0073 ..................................................... 23

5.1.4. Cabometyx - cabozantinib - EMEA/H/C/004163/II/0023 ............................................... 23

5.1.5. Dengvaxia - dengue tetravalent vaccine (live, attenuated) - EMEA/H/C/004171/II/0011 .. 23

5.1.6. Dengvaxia - dengue tetravalent vaccine (live, attenuated) - EMEA/H/C/004171/II/0012 .. 23

5.1.7. Elonva - corifollitropin alfa - EMEA/H/C/001106/II/0061 ............................................... 24

5.1.8. Ilaris - canakinumab - EMEA/H/C/001109/II/0075 ....................................................... 24

5.1.9. Kalydeco - ivacaftor - Orphan - EMEA/H/C/002494/II/0096 .......................................... 24

5.1.10. Keytruda - pembrolizumab - EMEA/H/C/003820/II/0110 .............................................. 25

5.1.11. Keytruda - pembrolizumab - EMEA/H/C/003820/II/0111 .............................................. 25

5.1.12. Opdivo - nivolumab - EMEA/H/C/003985/II/0100 ........................................................ 25

5.1.13. Opdivo - nivolumab - EMEA/H/C/003985/II/0107 ........................................................ 26

5.1.14. Rapiscan - regadenoson - EMEA/H/C/001176/II/0038 .................................................. 26

5.1.15. Revestive - teduglutide - Orphan - EMEA/H/C/002345/II/0054/G .................................. 26

5.1.16. Vyxeos liposomal - daunorubicin / cytarabine - Orphan - EMEA/H/C/004282/II/0018/G.... 26

5.1.17. Yescarta - axicabtagene ciloleucel - Orphan - ATMP - EMEA/H/C/004480/II/0042 ............ 27

5.1.18. WS2049/G Lacosamide UCB - lacosamide - EMEA/H/C/005243/WS2049/0009/G Vimpat -

lacosamide - EMEA/H/C/000863/WS2049/0091/G ....................................................... 27

5.1.19. WS2065 Delstrigo - doravirine / lamivudine / tenofovir disoproxil -

EMEA/H/C/004746/WS2065/0026 Pifeltro - doravirine - EMEA/H/C/004747/WS2065/001927

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5.1.20. WS2113 Opdivo - nivolumab - EMEA/H/C/003985/WS2113/0108 Yervoy - ipilimumab -
EMEA/H/C/002213/WS2113/0090 ............................................................................. 28

5.2. Update on on-going Type II variation; variation of therapeutic indication procedure

according to Commission Regulation (EC) No 1234/2008 .................................... 28

5.2.1. Tookad - padeliporfin - EMEA/H/C/004182/II/0013 ...................................................... 28

5.2.2. Keytruda - pembrolizumab - EMEA/H/C/003820/II/0109 .............................................. 29

5.3. Re-examination of Type II variation; variation of therapeutic indication procedure

according to Commission Regulation (EC) No 1234/2008 .................................... 29

6. Ancillary medicinal substances in medical devices 29

6.1. Ancillary medicinal substances in medical devices; Opinions/ Day 180 list of
outstanding issues / Day 120 list of questions ..................................................... 29

6.2. Update of Ancillary medicinal substances in medical devices ............................... 29

7. Procedure under Article 83(1) of Regulation (EC) 726/2004

(Compassionate Use) 29
7.1. Procedure under Article 83(1) of Regulation (EC) 726/2004 (Compassionate Use)29

8. Pre-submission issues 30
8.1. Pre-submission issue ............................................................................................ 30

8.1.1. etranacogene dezaparvovec - H0004827 .................................................................... 30

8.2. Priority Medicines (PRIME) ................................................................................... 30

8.2.1. List of applications received ...................................................................................... 30

8.2.2. Recommendation for PRIME eligibility......................................................................... 30

9. Post-authorisation issues 30
9.1. Post-authorisation issues ..................................................................................... 30

9.1.1. Rubraca - rucaparib - EMEA/H/C/004272/II/0029 ........................................................ 30

9.1.2. Ad-hoc assessment of the therapeutic effect of monoethyl fumarate salts within Fumaderm31

9.1.3. Piqray - alpelisib - EMEA/H/C/004804/II/0008/G ......................................................... 31

9.1.4. Ocaliva – obeticholic acid – EMEA/H/C/004093/R/0027 ................................................ 31

9.1.5. Cervarix - human papillomavirus vaccine [types 16, 18] (recombinant, adjuvanted, adsorbed)
- EMEA/H/C/000721/II/0110 ..................................................................................... 31

9.1.6. Leganto – Rotigotine – EMA/H/C/002380 .................................................................... 32

9.1.7. Nulojix - belatacept - EMEA/H/C/002098/II/0065/G ..................................................... 32

9.1.8. Kanuma - sebelipase alfa – Orphan – EMEA/H/C/004004/II/0032 .................................. 32

10. Referral procedures 33

10.1. Procedure for Centrally Authorised products under Article 20 of Regulation (EC) No
726/2004 ............................................................................................................. 33

10.2. Requests for CHMP Opinion under Article 5(3) of Regulation (EC) No 726/2004 . 33

10.3. Procedure under Articles 5(2) and 10 of Regulation (EC) No 726/2004 ............... 33

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10.4. Disagreement between Member States on application for medicinal product
(potential serious risk to public health) –under Article 29(4) of Directive
2001/83/EC ......................................................................................................... 33

10.5. Harmonisation - Referral procedure under Article 30 of Directive 2001/83/EC .... 33

10.6. Community Interests - Referral under Article 31 of Directive 2001/83/EC .......... 33

10.7. Re-examination Procedure under Article 32(4) of Directive 2001/83/EC ............. 33

10.8. Procedure under Article 107(2) of Directive 2001/83/EC .................................... 33

10.9. Disagreement between Member States on Type II variation– Arbitration procedure

initiated by MAH under Article 6(13) of Commission Regulation (EC) No 1084/2003
............................................................................................................................. 33

10.10. Procedure under Article 29 of Regulation (EC) 1901/2006................................... 34

10.11. Referral under Article 13 Disagreement between Member States on Type II

variation– Arbitration procedure initiated by Member State under Article 13 (EC) of
Commission Regulation No 1234/2008 ................................................................ 34

11. Pharmacovigilance issue 34

11.1. Early Notification System ..................................................................................... 34

12. Inspections 34
12.1. GMP inspections ................................................................................................... 34

12.2. GCP inspections .................................................................................................... 34

12.3. Pharmacovigilance inspections ............................................................................. 34

12.4. GLP inspections .................................................................................................... 34

13. Innovation Task Force 35

13.1. Minutes of Innovation Task Force ......................................................................... 35

13.2. Innovation Task Force briefing meetings.............................................................. 35

13.3. Requests for CHMP Opinion under Article 57(1)J and (1)P of Regulation (EC) No
726/2004 ............................................................................................................. 35

13.4. Nanomedicines activities ...................................................................................... 35

14. Organisational, regulatory and methodological matters 35

14.1. Mandate and organisation of the CHMP ................................................................ 35

14.1.1. Roles and responsibilities of CHMP members ............................................................... 35

14.2. Coordination with EMA Scientific Committees....................................................... 35

14.2.1. Pharmacovigilance Risk Assessment Committee (PRAC) ............................................... 35

14.2.2. Paediatric Committee (PDCO).................................................................................... 35

14.3. Coordination with EMA Working Parties/Working Groups/Drafting Groups ......... 36

14.3.1. Safety Working Party (SWP) ..................................................................................... 36

14.3.2. Biologics Working Party (BWP) .................................................................................. 36

14.3.3. Scientific Advice Working Party (SAWP) ...................................................................... 36

14.4. Cooperation within the EU regulatory network ..................................................... 36

14.4.1. Nitrosamines Multidisciplinary Expert Group (NMEG) on rifampicin ................................. 36

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14.5. Cooperation with International Regulators........................................................... 36

14.6. Contacts of the CHMP with external parties and interaction with the Interested
Parties to the Committee ...................................................................................... 37

14.7. CHMP work plan ................................................................................................... 37

14.8. Planning and reporting ......................................................................................... 37

14.9. Others .................................................................................................................. 37

15. Any other business 37

15.1. AOB topic .............................................................................................................. 37

15.1.1. Update on COVID-19 ............................................................................................... 37

15.1.2. Sotrovimab - EMEA/H/0005676 ................................................................................. 37

15.1.3. COVID-19 vaccine - EMEA/H/C/005754 ...................................................................... 37

15.1.4. COVID-19 vaccine (NVX-CoV2373) – EMEA/H/C/005808 .............................................. 37

Explanatory notes 38

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1. Introduction

1.1. Welcome and declarations of interest of members, alternates and

experts

Pre-meeting list of participants and restrictions in relation to declarations of interests

applicable to the items of the agenda for the CHMP plenary session to be held 08-11
November 2021. See November 2021 CHMP minutes (to be published post December 2021
CHMP meeting).

1.2. Adoption of agenda

CHMP agenda for 08-11 November 2021

1.3. Adoption of the minutes

CHMP minutes for 11-14 October 2021.

Minutes from PReparatory and Organisational Matters (PROM) meeting held on 03

November 2021.

2. Oral Explanations

2.1. Pre-authorisation procedure oral explanations

2.1.1. aducanumab - EMEA/H/C/005558

Alzheimer’s disease

Scope: Oral explanation

Action: Oral explanation to be held on 09 November 2021 at 16:00

List of Outstanding Issues adopted on 22.07.2021. List of Questions adopted on

25.02.2021.

2.1.2. tepotinib - EMEA/H/C/005524

treatment of advanced non-small cell lung cancer

Scope: Oral explanation

Action: Oral explanation to be held on 09 November 2021 at 11:00

List of Outstanding Issues adopted on 16.09.2021. List of Questions adopted on

25.03.2021.

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2.1.3. inebilizumab - Orphan - EMEA/H/C/005818

Viela Bio; indicated for the treatment of adults with neuromyelitis optica spectrum disorders

Scope: Possible oral explanation

Action: Possible oral explanation to be held on 09 November 2021 at 14:00

List of Outstanding Issues adopted on 16.09.2021. List of Questions adopted on

22.04.2021.

2.1.4. casirivimab / imdevimab - EMEA/H/C/005814

prevention and treatment of COVID-19

Scope: Possible oral explanation

Action: Possible oral explanation to be held on 08 November 2021 at 14:00

2.2. Re-examination procedure oral explanations

2.2.1. Nouryant - istradefylline - EMEA/H/C/005308

Kyowa Kirin Holdings B.V.; indicated as an adjunctive treatment to levodopa-based

regimens in patients with Parkinson’s disease

Scope: Oral explanation/Opinion

Action: Oral explanation to be held on 09 November 2021 at 09:00

New active substance (Article 8(3) of Directive No 2001/83/EC)

Opinion adopted on 22.07.2021. List of Outstanding Issues adopted on 25.02.2021. List of

Questions adopted on 30.04.2020.

See 3.5

2.2.2. Nexviadyme - avalglucosidase alfa - Orphan - EMEA/H/C/005501

Genzyme Europe BV; for long-term enzyme replacement therapy for the treatment of
patients with Pompe disease.

Scope: Oral explanation/Opinion

Action: Oral explanation to be held on 08 November 2021 at 16:00

New active substance (Article 8(3) of Directive No 2001/83/EC)

Opinion adopted on 23.07.2021. List of Outstanding Issues adopted on 20.05.2021. List of

Questions adopted on 28.01.2021.

See 3.5

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2.3. Post-authorisation procedure oral explanations

2.3.1. Ferriprox - deferiprone - EMEA/H/C/000236/X/0145

Chiesi Farmaceutici S.p.A.

Rapporteur: Alexandre Moreau, PRAC Rapporteur: Tiphaine Vaillant

Scope: “Extension application to introduce a new pharmaceutical form (gastro-resistant

tablets). The RMP (version 14.0) is updated in accordance.”

Oral explanation

Action: Oral explanation to be held on 10 November 2021 at time 15:30

List of Outstanding Issues adopted on 14.10.2021, 24.06.2021, 25.02.2021. List of

Questions adopted on 17.09.2020.

See 4.1

2.4. Referral procedure oral explanations

No items

3. Initial applications

3.1. Initial applications; Opinions

3.1.1. bevacizumab - EMEA/H/C/005433

indicated in adults for the treatment of neovascular macular degeneration associated with
aging and diabetes.

Scope: Opinion

Action: For adoption

List of Outstanding Issues adopted on 20.05.2021. List of Questions adopted on

17.09.2020.

3.1.2. finerenone - EMEA/H/C/005200

delay progression of kidney disease, reduce the risk of cardiovascular mortality and
morbidity

Scope: Opinion

Action: For adoption

List of Outstanding Issues adopted on 16.09.2021. List of Questions adopted on

25.03.2021.

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3.1.3. sotorasib - EMEA/H/C/005522

treatment of locally advanced or metastatic non-small cell lung cancer

Scope: Opinion

Action: For adoption

List of Outstanding Issues adopted on 16.09.2021. List of Questions adopted on

20.05.2021.

3.1.4. regdanvimab - EMEA/H/C/005854

Treatment of COVID-19

Scope: Opinion

Action: For adoption

3.1.5. formoterol fumarate dihydrate / glycopyrronium / budesonide - EMEA/H/C/005311

maintenance treatment of chronic obstructive pulmonary disease (COPD)

Scope: Opinion

Action: For adoption

3.1.6. avacopan - Orphan - EMEA/H/C/005523

Vifor Fresenius Medical Care Renal Pharma France; Treatment of granulomatosis with
polyangiitis (GPA) or microscopic polyangiitis (MPA)

Scope: Opinion

Action: For adoption

List of Outstanding Issues adopted on 14.10.2021, 22.07.2021. List of Questions adopted

on 25.02.2021.

3.1.7. tecovirimat - EMEA/H/C/005248

treatment of orthopoxvirus disease

Scope: Opinion

Action: For adoption

List of Outstanding Issues adopted on 22.07.2021. List of Questions adopted on

25.02.2021.

3.1.8. glucarpidase - Orphan - EMEA/H/C/005467

Serb; treatment of patients at risk of methotrexate toxicity

Scope: Opinion

Action: For adoption

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 List of Outstanding Issues adopted on 16.09.2021, 24.06.2021. List of Questions adopted
on 10.12.2020.

3.1.9. eptinezumab - EMEA/H/C/005287

Indicated for the prophylaxis of migraine in adults

Scope: Opinion

Action: For adoption

List of Outstanding Issues adopted on 16.09.2021. List of Questions adopted on

22.04.2021.

3.1.10. semaglutide - EMEA/H/C/005422

treatment for weight loss and weight maintenance

Scope: Opinion

Action: For adoption

List of Outstanding Issues adopted on 14.10.2021. List of Questions adopted on

20.05.2021.

3.2. Initial applications; List of outstanding issues (Day 180; Day 120 for
procedures with accelerated assessment timetable)

3.2.1. pneumococcal polysaccharide conjugate vaccine (20-valent, adsorbed) -

EMEA/H/C/005451

prevention of invasive disease and pneumonia caused by Streptococcus pneumoniae

serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F
and 33F

Scope: List of outstanding issues

Action: For adoption

List of Questions adopted on 22.07.2021.

3.2.2. dengue tetravalent vaccine (live, attenuated) - Article 58 - EMEA/H/W/005362

prevention of dengue disease

Scope: List of outstanding issues

Action: For adoption

List of Questions adopted on 24.06.2021.

Committee for medicinal products for human use (CHMP)

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3.2.3. betulae cortex dry extract (5-10: 1); extraction solvent: n-heptane 95% (w/w) -
Orphan - EMEA/H/C/005035

Amryt Pharmaceuticals DAC; Treatment to achieve accelerated healing of wounds

associated with dystrophic and junctional epidermolysis bullosa (EB) in patients from birth
onwards.

Scope: List of outstanding issues

Action: For adoption

List of Questions adopted on 22.07.2021.

3.2.4. lonapegsomatropin - Orphan - EMEA/H/C/005367

Ascendis Pharma Endocrinology Division A/S; Treatment of growth hormone deficiency

Scope: List of outstanding issues

Action: For adoption

List of Outstanding Issues adopted on 16.09.2021, 24.06.2021. List of Questions adopted

on 28.01.2021.

3.2.5. somatrogon - Orphan - EMEA/H/C/005633

Pfizer Europe MA EEIG; indicated for the long-term treatment of paediatric patients with
growth disturbance due to insufficient secretion of growth hormone.

Scope: List of outstanding issues

Action: For adoption

List of Questions adopted on 24.06.2021.

3.2.6. dengue tetravalent vaccine (live, attenuated) - EMEA/H/C/005155

prevention of dengue disease

Scope: List of outstanding issues

Action: For adoption

List of Questions adopted on 24.06.2021.

3.2.7. pegfilgrastim - EMEA/H/C/004780

treatiment of neutropenia

Scope: List of outstanding issues

Action: For adoption

List of Questions adopted on 17.09.2020.

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3.2.8. eladocagene exuparvovec - Orphan - ATMP - EMEA/H/C/005352

PTC Therapeutics International Limited; treatment of aromatic L-amino aciddecarboxylase

(AADC) deficiency

Scope: List of outstanding issues

Action: For adoption

List of Outstanding Issues adopted on 16.04.2021. List of Questions adopted on

20.05.2020.

3.2.9. linzagolix choline - EMEA/H/C/005442

for the management of heavy menstrual bleeding (HMB) associated with uterine fibroids

Scope: List of outstanding issues

Action: For adoption

List of Outstanding Issues adopted on 16.09.2021. List of Questions adopted on

22.04.2021.

3.2.10. rimegepant - EMEA/H/C/005725

management of migraine

Scope: List of outstanding issues

Action: For adoption

List of Questions adopted on 24.06.2021.

3.3. Initial applications; List of questions (Day 120; Day 90 for

procedures with accelerated assessment timetable)

3.3.1. insulin human - Article 58 - EMEA/H/W/005779

treatment of diabetes mellitus

Scope: List of questions

Action: For adoption

3.3.2. asciminib - Orphan - EMEA/H/C/005605

Novartis Europharm Limited; treatment of Philadelphia chromosome-positive chronic

myeloid leukaemia in chronic phase (Ph+ CML-CP)

Scope: List of questions

Action: For adoption

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3.3.3. mobocertinib - EMEA/H/C/005621

Treatment of adult patients with epidermal growth factor receptor (EGFR) exon 20 insertion
mutation-positive locally advanced or metastatic non-small cell lung cancer (NSCLC).

Scope: List of questions

Action: For adoption

3.3.4. eptacog alfa (activated) - EMEA/H/C/005547

treatment of bleeding episodes and for the prevention of bleeding

Scope: List of questions

Action: For adoption

3.3.5. insulin human - Article 58 - EMEA/H/W/005780

treatment of diabetes mellitus

Scope: List of questions

Action: For adoption

3.3.6. tebentafusp - Orphan - EMEA/H/C/004929

Accelerated assessment

Immunocore Ireland Limited; treatment of uveal melanoma

Scope: List of questions

Action: For adoption

3.3.7. voclosporin - EMEA/H/C/005256

indicated in combination with background immunosuppressive therapies for the treatment

of adult patients with class III, IV or V (including mixed class III/V and IV/V) lupus nephritis
(LN).

Scope: List of questions

Action: For adoption

3.3.8. mitapivat - Orphan - EMEA/H/C/005540

Agios Netherlands B.V.; treatment of pyruvate kinase deficiency

Scope: List of questions

Action: For adoption

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3.3.9. ranibizumab - EMEA/H/C/005019

The treatment of neovascular (wet) age-related macular degeneration (AMD), visual

impairment due to diabetic macular oedema (DME), proliferative diabetic retinopathy (PDR),
visual impairment due to macular oedema secondary to retinal vein occlusion (branch RVO
or central RVO) and visual impairment due to choroidal neovascularisation (CNV)

Scope: List of questions

Action: For adoption

3.3.10. valoctocogene roxaparvovec - Orphan - ATMP - EMEA/H/C/005830

Accelerated assessment

BioMarin International Limited; treatment of severe haemophilia A

Scope: List of questions

Action: For information

3.3.11. surufatinib - EMEA/H/C/005728

treatment of progressive neuroendocrine tumours

Scope: List of questions

Action: For adoption

3.3.12. sorafenib - EMEA/H/C/005921

treatment of hepatocellular carcinoma and renal cell carcinoma

Scope: List of questions

Action: For adoption

3.4. Update on on-going initial applications for Centralised procedure

3.4.1. sodium thiosulfate - PUMA - EMEA/H/C/005130

for the prevention of ototoxicity induced by cisplatin (CIS) chemotherapy in patients 1

month to < 18 years of age with localized, non-metastatic, solid tumours.

Scope: Call for expression of interest for additional experts for the SAG-Oncology.

The list of experts will be adopted via written procedure.

Action: For information

List of Outstanding Issues adopted on 24.06.2021. List of Questions adopted on

25.06.2020.

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3.4.2. melphalan flufenamide - Orphan - EMEA/H/C/005681

Oncopeptides AB; treatment of multiple myeloma

Scope: Letter from the applicant dated 04 November 2021 requesting an extension to the
clock stop to respond to the list of questions adopted in September 2021.

Action: For adoption

List of questions adopted on 16.09.2021.

3.4.3. lenadogene nolparvovec - Orphan - ATMP - EMEA/H/C/005047

GenSight Biologics S.A.; treatment of vision loss due to Leber Hereditary Optic Neuropathy
(LHON)

Scope: Letter from the applicant dated 20 October 2021 requesting an extension of clock-
stop to respond to the list of questions adopted in February 2021.

Action: For information

List of Questions adopted on 25.02.2021.

3.5. Re-examination of initial application procedures under Article 9(2)

of Regulation no 726/2004

3.5.1. Nouryant - istradefylline - EMEA/H/C/005308

Kyowa Kirin Holdings B.V.; indicated as an adjunctive treatment to levodopa-based

regimens in patients with Parkinson’s disease

Scope: Oral explanation/Opinion

Action: For adoption

New active substance (Article 8(3) of Directive No 2001/83/EC)

Opinion adopted on 22.07.2021. List of Outstanding Issues adopted on 25.02.2021. List of

Questions adopted on 30.04.2020.

See 2.2

3.5.2. Nexviadyme - avalglucosidase alfa - Orphan - EMEA/H/C/005501

Genzyme Europe BV; for long-term enzyme replacement therapy for the treatment of
patients with Pompe disease.

Scope: Oral explanation/Opinion

Action: For adoption

New active substance (Article 8(3) of Directive No 2001/83/EC)

Opinion adopted on 23.07.2021. List of Outstanding Issues adopted on 20.05.2021. List of

Questions adopted on 28.01.2021.

See 2.2

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3.6. Initial applications in the decision-making phase

No items

3.7. Withdrawals of initial marketing authorisation application

No items

4. Extension of marketing authorisation according to Annex I of

Commission Regulation (EC) No 1234/2008

4.1. Extension of marketing authorisation according to Annex I of

Commission Regulation (EC) No 1234/2008; Opinion

4.1.1. Adynovi - rurioctocog alfa pegol - EMEA/H/C/004195/X/0018

Baxalta Innovations GmbH

Rapporteur: Andrea Laslop, PRAC Rapporteur: Menno van der Elst

Scope: “Extension application to add a new strength of 3000 IU for RURIOCTOCOG ALFA
PEGOL powder and solvent for solution for injection, for intravenous use.
Furthermore, the MAH took the opportunity to include editorial changes to update the
naming convention from BAX855 to rurioctocog alfa pegol throughout the section and
removed the reference to Baxalta as well as update table numbering throughout the
documents in module 3. Furthermore, changes omitted from the dossier following approval
of variations EMEA/H/C/004195/IB/0004/G and EMEA/H/C/004195/IB/0015/G were also
included.”

Action: For adoption

List of Outstanding Issues adopted on 16.09.2021. List of Questions adopted on

22.04.2021.

4.1.2. Dupixent - dupilumab - EMEA/H/C/004390/X/0045/G

sanofi-aventis groupe

Rapporteur: Jan Mueller-Berghaus, PRAC Rapporteur: Kimmo Jaakkola

Scope: “1- Extension of a marketing authorisation for Dupixent to add a new strength, 100
mg solution for injection.
2- Type II (C.I.6) - Extension of indication to include treatment of paediatric patients with
severe asthma with type 2 inflammation aged 6 to 11 years old.
Version 6.0 of the RMP has also been submitted.”

Action: For adoption

List of Questions adopted on 22.07.2021.

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4.1.3. Epclusa - sofosbuvir / velpatasvir - EMEA/H/C/004210/X/0056/G

Gilead Sciences Ireland UC

Rapporteur: Filip Josephson, PRAC Rapporteur: Ana Sofia Diniz Martins

Scope: “Extension application to introduce a new pharmaceutical form (coated granules in

sachet) associated with strengths 200 mg/50 mg and 150 mg/37.5 mg. The new
presentations are indicated for the treatment of chronic hepatitis C virus (HCV) infection in
patients 3 years of age and older. The extension application is grouped with a type II
variation (C.I.6.a) to include paediatric use in patients 3 years of age and older to the
existing presentations of the film-coated tablets. Sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the
SmPC and the Package Leaflet are updated to support the extended indication.
The RMP (version 7.1) is updated in accordance.
In addition, the MAH took the opportunity to implement minor updates and corrections
throughout the Product Information.”

Action: For adoption

List of Questions adopted on 22.07.2021.

4.1.4. Ferriprox - deferiprone - EMEA/H/C/000236/X/0145

Chiesi Farmaceutici S.p.A.

Rapporteur: Alexandre Moreau, PRAC Rapporteur: Tiphaine Vaillant

Scope: “Extension application to introduce a new pharmaceutical form (gastro-resistant

tablets). The RMP (version 14.0) is updated in accordance.”

Action: For adoption

List of Outstanding Issues adopted on 14.10.2021, 24.06.2021, 25.02.2021. List of

Questions adopted on 17.09.2020.

See 2.3

4.1.5. Kaftrio - ivacaftor / tezacaftor / elexacaftor - Orphan - EMEA/H/C/005269/X/0008/G

Vertex Pharmaceuticals (Ireland) Limited

Rapporteur: Johann Lodewijk Hillege, PRAC Rapporteur: Martin Huber

Scope: “Extension application to introduce a new strength of 37.5 mg/25 mg/50 mg film-
coated tablets; grouped with a type II variation (C.I.6.a) to include paediatric use (6 to 11
years).”

Action: For adoption

List of Outstanding Issues adopted on 14.10.2021. List of Questions adopted on

22.07.2021.

4.1.6. Noxafil - posaconazole - EMEA/H/C/000610/X/0063/G

Merck Sharp & Dohme B.V.

Rapporteur: Alexandre Moreau, PRAC Rapporteur: Tiphaine Vaillant

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 Scope: “Extension application to introduce a new pharmaceutical form (gastro-resistant
powder and solvent for oral suspension), grouped with a type II variation (C.I.6.a) to
extend the approved indications for Noxafil to the paediatric population.
As a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC, as well as the package
leaflet, are updated. The RMP (version 17.1) is updated in accordance.”

Action: For adoption

List of Outstanding Issues adopted on 22.07.2021. List of Questions adopted on

25.03.2021.

4.1.7. Nuwiq - simoctocog alfa - EMEA/H/C/002813/X/0042

Octapharma AB

Rapporteur: Jan Mueller-Berghaus

Scope: “Extension application to add a new strength of 1500 IU for simoctocog alfa powder
and solvent for solution for injection, for Intravenous use.
The marketing authorisation holder took the opportunity to align the PI to the latest QRD
template (version 10.2).”

Action: For adoption

List of Outstanding Issues adopted on 16.09.2021. List of Questions adopted on

24.06.2021.

4.1.8. Ozempic - semaglutide - EMEA/H/C/004174/X/0021

Novo Nordisk A/S

Rapporteur: Johann Lodewijk Hillege, Co-Rapporteur: Sinan B. Sarac, PRAC Rapporteur:

Annika Folin

Scope: “Extension application to add a new strength of 2 mg solution for injection.”

Action: For adoption

List of Outstanding Issues adopted on 14.10.2021. List of Questions adopted on

20.05.2021.

4.2. Extension of marketing authorisation according to Annex I of

Commission Regulation (EC) No 1234/2008; Day 180 list of
outstanding issues

4.2.1. Ayvakyt - avapritinib - Orphan - EMEA/H/C/005208/X/0004/G

Blueprint Medicines (Netherlands) B.V.

Rapporteur: Blanca Garcia-Ochoa, Co-Rapporteur: Ingrid Wang, PRAC Rapporteur: Menno

van der Elst

Scope: “Extension application to add two new strengths of film-coated tablets (25 mg and
50 mg), grouped with a type II variation (C.I.6.a) to introduce a new therapeutic indication
for Ayvakyt. Extension of indication to include treatment of adult patients with advanced

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 systemic mastocytosis (AdvSM), including aggressive systemic mastocytosis (ASM),
systemic mastocytosis with an associated haematological neoplasm (SM-AHN), and mast
cell leukaemia (MCL), after at least one systemic therapy for Ayvakyt based on the results
of the BLU-285-2101 and BLU-285-2202 studies. The new indication is applicable to the
new and existing presentations (25 mg, 50 mg, 100 mg and 200 mg film-coated tablets).
As a consequence, sections 1, 2, 3, 4.1, 4.2, 4.4, 4.5, 4.6, 4.8, 5.1, 5.2, 5.3, 6.1 and 8 of
the SmPC are updated. The Labelling and Package Leaflet are updated in accordance.
Version 1.1 of the RMP has also been submitted.”

Action: For adoption

List of Questions adopted on 24.06.2021.

4.3. Extension of marketing authorisation according to Annex I of

Commission Regulation (EC) No 1234/2008; Day 120 List of
question

4.3.1. Genvoya - elvitegravir / cobicistat / emtricitabine / tenofovir alafenamide -

EMEA/H/C/004042/X/0079/G

Gilead Sciences Ireland UC

Rapporteur: Bruno Sepodes, PRAC Rapporteur: Ilaria Baldelli

Scope: “Extension application to introduce a new strength (90 mg/90 mg/120 mg/6 mg
film-coated tablets). The extension application is grouped with a type II variation (C.I.6.a)
to include treatment of human immunodeficiency virus 1 (HIV 1) infection without any
known mutations associated with resistance to the integrase inhibitor class, emtricitabine or
tenofovir in paediatric patients aged from 2 years and with body weight at least 14 kg.
Sections 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC and the Package Leaflet are updated to
support the extended indication. The RMP (version 5.1) is updated in accordance.”

Action: For adoption

4.3.2. Ilumetri - tildrakizumab - EMEA/H/C/004514/X/0023

Almirall S.A

Rapporteur: Jan Mueller-Berghaus, PRAC Rapporteur: Adam Przybylkowski

Scope: “Extension application to introduce a new strength (200 mg solution for injection).”

Action: For adoption

4.3.3. Procysbi - mercaptamine - Orphan - EMEA/H/C/002465/X/0035

Chiesi Farmaceutici S.p.A.

Rapporteur: Kristina Dunder, PRAC Rapporteur: Ulla Wändel Liminga

Scope: “Extension application to introduce a new pharmaceutical form associated with two
new strengths (75 and 300 mg gastro-resistant granules). The RMP (version 7.2) is updated
in accordance.”

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 Action: For adoption

4.4. Update on on-going extension application according to Annex I of

Commission Regulation (EC) No 1234/2008

No items

4.5. Re-examination procedure of extension of marketing authorisation

according to Annex I of Commission Regulation (EC) No 1234/2008

No items

5. Type II variations - variation of therapeutic indication

procedure according to Annex I of Commission Regulation
(EC) No 1234/2008

5.1. Type II variations - variation of therapeutic indication procedure

according to Commission Regulation (EC) No 1234/2008; Opinions
or Requests for supplementary information

5.1.1. Beovu - brolucizumab - EMEA/H/C/004913/II/0010

Novartis Europharm Limited

Rapporteur: Alexandre Moreau, PRAC Rapporteur: Brigitte Keller-Stanislawski

Scope: “Extension of indication to include treatment of visual impairment due to DME for
Beovu; as a consequence, sections 4.1, 4.4, 4.8, and 5.1 of the SmPC are updated. The
Package Leaflet is updated in accordance. Version 4.0 of the RMP has also been submitted.”

Action: For adoption

5.1.2. Briviact - brivaracetam - EMEA/H/C/003898/II/0032/G

UCB Pharma S.A.

Rapporteur: Filip Josephson, PRAC Rapporteur: Adam Przybylkowski

Scope: “- Extension of indication to include patients from 1 month to 4 years of age for the
Briviact treatment; as a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are
updated. The RMP version 8.0 has also been submitted. Furthermore, the PI is brought in
line with the latest QRD template version 10.2 and the MAH took the opportunity to
implement minor editorial updates.
- (B.II.f.1.b.2)
- (B.IV.1.a.1)
The Package Leaflet and Labelling are updated in accordance.”

Action: For adoption

Request for Supplementary Information adopted on 16.09.2021, 24.06.2021.

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5.1.3. Bydureon - exenatide - EMEA/H/C/002020/II/0073

AstraZeneca AB

Rapporteur: Kristina Dunder, PRAC Rapporteur: Annika Folin

Scope: “Extension of indication to include the treatment of adolescents and children aged
10 years and above based on the results from study BCB114 (D5551C00002); a phase 3,
double-blind, placebo-controlled, randomized, multi-center study to assess the safety and
efficacy of exenatide once weekly in adolescents with type 2 diabetes, which was initially
submitted and assessed by the CHMP as part of the post-authorisation measure (PAM) P46
028. As a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are updated and
the Package Leaflet is updated in accordance. Version 35s1 of the RMP has also been
submitted.”

Action: For adoption

5.1.4. Cabometyx - cabozantinib - EMEA/H/C/004163/II/0023

Ipsen Pharma

Rapporteur: Ingrid Wang, PRAC Rapporteur: Menno van der Elst

Scope: “Extension of indication to include monotherapy treatment of adults and adolescent

patients aged 12 years and older, with locally advanced or metastatic differentiated thyroid
carcinoma (DTC), refractory or not eligible to radioactive iodine (RAI) who have progressed
during or after prior systemic therapy for Cabometyx; as a consequence, sections 4.1, 4.2,
4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in
accordance. Version 6.0 of the RMP has also been submitted.”

Action: For adoption

5.1.5. Dengvaxia - dengue tetravalent vaccine (live, attenuated) -

EMEA/H/C/004171/II/0011

Sanofi Pasteur

Rapporteur: Christophe Focke

Scope: “To modify the approved therapeutic indication to include conditions for the
eligibility to pre-vaccination serostatus screening. As a consequence, sections 4.1, 4.2 and
4.4 of the SmPC and sections 1, 2 and 3 of the Package Leaflet are updated accordingly.”

Action: For adoption

Request for Supplementary Information adopted on 20.05.2021, 10.12.2020.

5.1.6. Dengvaxia - dengue tetravalent vaccine (live, attenuated) -

EMEA/H/C/004171/II/0012

Sanofi Pasteur

Rapporteur: Christophe Focke

Scope: “Extension of indication to include paediatric population from 6 years of age for
Dengvaxia; as a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC and sections 1, 2

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 and 4 of the Package Leaflet are updated. Furthermore, the MAH takes the opportunity to
add an instruction for the installation of the needle in the SmPC and the Package Leaflet of
the single-dose presentation.”

Action: For adoption

Request for Supplementary Information adopted on 20.05.2021, 10.12.2020.

5.1.7. Elonva - corifollitropin alfa - EMEA/H/C/001106/II/0061

Organon N.V.

Rapporteur: Paula Boudewina van Hennik, Co-Rapporteur: Peter Kiely, PRAC Rapporteur:
Menno van der Elst

Scope: “Extension of indication to include treatment of adolescent males (14 to less than 18
years) with hypogonadotropic hypogonadism, in combination with human Chorionic
Gonadotropin (hCG) for Elonva, based on final results of the paediatric study P043. Study
P043 was an open-label, non-comparative, multi-center safety and efficacy study of
corifollitropin in association with hCG in male adolescents with hypogonadotropic
hypogonadism, part of the paediatric investigation plan; as a consequence, sections 4.1,
4.2, 4.4, 4.6, 4.8, 4.9, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is
updated in accordance. Version 9.2 of the RMP has also been submitted. In addition, the
Marketing authorisation holder (MAH) took the opportunity to implement some minor
editorial and formatting changes throughout the PI.”

Action: For adoption

5.1.8. Ilaris - canakinumab - EMEA/H/C/001109/II/0075

Novartis Europharm Limited

Rapporteur: Jan Mueller-Berghaus, Co-Rapporteur: Outi Mäki-Ikola, PRAC Rapporteur:

Brigitte Keller-Stanislawski

Scope: “Extension of indication to include treatment of adult patients with Schnitzler

syndrome for Ilaris; as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC
are updated. The Package Leaflet is updated in accordance. Version 13.0 of the RMP has
also been submitted.”

Action: For adoption

5.1.9. Kalydeco - ivacaftor - Orphan - EMEA/H/C/002494/II/0096

Vertex Pharmaceuticals (Ireland) Limited

Rapporteur: Agnes Gyurasics, PRAC Rapporteur: Maria del Pilar Rayon

Scope: “Extension of indication for Kalydeco tablets in combination regiment with Kaftrio to
include the treatment of adults, adolescents and children aged 6 years and older with cystic
fibrosis who are homozygous for the F508del mutation in the CFTR gene or heterozygous
for F508del and have a minimal function (MF) mutation in the CFTR gene. This application is
based on the results of study VX18-445-106, a phase 3, open-label, multicentre study in
subjects 6 through 11 years of age, with F/MF and F/F genotypes. As a consequence,

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 sections 4.1, 4.2, 5.1 and 5.2 of the SmPC are updated. The Packaged Leaflet is updated in
accordance. Version 12.0 of the RMP has also been submitted.”

Action: For adoption

Request for Supplementary Information adopted on 14.10.2021, 22.07.2021.

5.1.10. Keytruda - pembrolizumab - EMEA/H/C/003820/II/0110

Merck Sharp & Dohme B.V.

Rapporteur: Armando Genazzani, Co-Rapporteur: Jan Mueller-Berghaus, PRAC Rapporteur:

Menno van der Elst

Scope: “Extension of indication for Keytruda in combination with chemotherapy as

neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after
surgery of adults with locally advanced, inflammatory, or early-stage triple-negative breast
cancer at high-risk of recurrence; as a consequence, sections 4.1, 4.2 and 5.1 of the SmPC
are updated. The Package Leaflet is updated in accordance. Version 37.1 of the RMP has
also been submitted.”

Action: For adoption

5.1.11. Keytruda - pembrolizumab - EMEA/H/C/003820/II/0111

Merck Sharp & Dohme B.V.

Rapporteur: Armando Genazzani, Co-Rapporteur: Jan Mueller-Berghaus, PRAC Rapporteur:

Menno van der Elst

Scope: “Extension of indication to include the adjuvant treatment of adults and adolescents
aged 12 years and older with Stage IIB, Stage IIC or stage III melanoma and to include the
treatment of adolescents aged 12 years and older with advanced melanoma for Keytruda;
as a consequence, sections 4.1, 4.2 and 5.1 of the SmPC are updated. The Package Leaflet
is updated in accordance. Version 36.1 of the RMP has also been submitted.”

Action: For adoption

5.1.12. Opdivo - nivolumab - EMEA/H/C/003985/II/0100

Bristol-Myers Squibb Pharma EEIG

Rapporteur: Paula Boudewina van Hennik, PRAC Rapporteur: Brigitte Keller-Stanislawski

Scope: “Extension of indication for Opdivo to include adjuvant treatment of adults with
muscle invasive urothelial carcinoma (MIUC) who are at high risk of recurrence after
undergoing radical resection of MIUC; as a consequence, sections 4.1, 4.2, 4.4, 4.8 and 5.1
of the SmPC are updated. The Package Leaflet is updated in accordance. Version 23.0 of the
RMP has also been submitted.”

Action: For adoption

Request for Supplementary Information adopted on 24.06.2021.

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5.1.13. Opdivo - nivolumab - EMEA/H/C/003985/II/0107

Bristol-Myers Squibb Pharma EEIG

Rapporteur: Blanca Garcia-Ochoa, PRAC Rapporteur: Brigitte Keller-Stanislawski

Scope: “Extension of indication to include in combination with fluoropyrimidine- and

platinum-based combination chemotherapy the first-line treatment of adult patients with
unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma
(OSCC) for Opdivo based on study CA209648; as a consequence, sections 4.1, 4.2, 4.4,
4.8, 5.1 and 6.6 of the SmPC are updated. The Package Leaflet is updated in accordance.
Version 25.0 of the RMP has also been submitted.”

Action: For adoption

5.1.14. Rapiscan - regadenoson - EMEA/H/C/001176/II/0038

GE Healthcare AS

Rapporteur: Maria Concepcion Prieto Yerro, Co-Rapporteur: Jayne Crowe

Scope: “Modification of existing indication to allow use in line with new imaging technologies
that have evolved since initial approval of Rapiscan; as a consequence, sections 4.1, 4.2
and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance.”

Action: For adoption

Request for Supplementary Information adopted on 22.07.2021.

5.1.15. Revestive - teduglutide - Orphan - EMEA/H/C/002345/II/0054/G

Shire Pharmaceuticals Ireland Limited

Rapporteur: Sinan B. Sarac, PRAC Rapporteur: Anette Kirstine Stark

Scope: “Extension of indication to include patients from 4 months corrected gestational

aged 1 year and above. Consequently sections 4.1, 4.2, 4.8, 5.1 and 5.2 are updated. The
Package leaflet is updated accordingly. Update of annex II to amend the date of completion
of the post-authorisation study. The MAH took the opportunity to also amend local
representatives.”

Action: For adoption

5.1.16. Vyxeos liposomal - daunorubicin / cytarabine - Orphan -

EMEA/H/C/004282/II/0018/G

Jazz Pharmaceuticals Ireland Limited

Rapporteur: Johanna Lähteenvuo, Co-Rapporteur: Janet Koenig, PRAC Rapporteur: Marcia

Sofia Sanches de Castro Lopes Silva

Scope: “Extension of indication to add treatment of relapsed/refractory AML in paediatric

patients with subsequent updates to sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC based
on the new safety and efficacy data from the paediatric clinical study AAML1421. The
Package leaflet is updated accordingly. The RMP version 1.1 has also been submitted. In
addition, the PI is updated in line with the latest QRD template 10.2.

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 Submission of the final data from paediatric clinical study CPX-MA-1201 in support of the
extension of indication.” Request for 1 year of market protection for a new indication
(Article 14(11) of Regulation (EC) 726/2004)

Action: For adoption

Request for Supplementary Information adopted on 20.05.2021.

5.1.17. Yescarta - axicabtagene ciloleucel - Orphan - ATMP - EMEA/H/C/004480/II/0042

Kite Pharma EU B.V.

Rapporteur: Jan Mueller-Berghaus, Co-Rapporteur: Claire Beuneu, PRAC Rapporteur: Anette

Kirstine Stark

Scope: “Extension of indication to include the treatment of adult patients with relapsed or
refractory follicular lymphoma (FL) after three or more lines of systemic therapy.
Consequently, sections 4.1, 4.8, 5.1 and 5.2 of the SmPC, Annex II (Section D) and
Package Leaflet are proposed to be updated. As a consequence, the RMP (version 5.1) has
been updated to align with the indication extension.
In addition, the applicant has taken the opportunity to make minor editorial corrections
throughout the SmPC and package leaflet to align with the current Quality Review of
Documents (QRD) template.” Request for 1 year of market protection for a new indication
(Article 14(11) of Regulation (EC) 726/2004)

Action: For adoption

5.1.18. WS2049/G
Lacosamide UCB - lacosamide - EMEA/H/C/005243/WS2049/0009/G
Vimpat - lacosamide - EMEA/H/C/000863/WS2049/0091/G

UCB Pharma S.A.

Lead Rapporteur: Filip Josephson

Scope: “Extension of indication to include patients from 1 month to 4 years of age for
treatment of partial-onset seizures with or without secondary generalisation as
monotherapy and adjunctive therapy for Vimpat/Lacosamide USB. As a consequence,
sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are updated. Version 16.0 of the RMP has
also been submitted.
B.IV.1.a.1
B.II.f.1.b.2
The Package Leaflet and labelling are updated in accordance.”

Action: For adoption

Request for Supplementary Information adopted on 16.09.2021, 24.06.2021.

5.1.19. WS2065
Delstrigo - doravirine / lamivudine / tenofovir disoproxil -
EMEA/H/C/004746/WS2065/0026
Pifeltro - doravirine - EMEA/H/C/004747/WS2065/0019

Merck Sharp & Dohme B.V.

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 Lead Rapporteur: Filip Josephson

Scope: “Extension of indication to include the new indication to the paediatric population
weighing at least 35 kgs for Pifeltro and Delstrigo. Sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the
SmPC are updated. The Package Leaflet is updated in accordance. Version 2.1 of the RMP
for each product have also been submitted. In addition, the Marketing authorisation holder
(MAH) took the opportunity to make minor editorial corrections and to update the list of
local representatives in the Package Leaflet.”

Action: For adoption

5.1.20. WS2113
Opdivo - nivolumab - EMEA/H/C/003985/WS2113/0108
Yervoy - ipilimumab - EMEA/H/C/002213/WS2113/0090

Bristol-Myers Squibb Pharma EEIG

Lead Rapporteur: Blanca Garcia-Ochoa

Scope: “Extension of indication to include first-line treatment of adult patients with

unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma
(OSCC) for Opdivo in combination with Yervoy; as a consequence, sections 4.1, 4.2, 4.4,
4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance.
Version 24.0 of the Opdivo RMP and version 33.0 of the Yervoy RMP have also been
submitted.”

Action: For adoption

5.2. Update on on-going Type II variation; variation of therapeutic

indication procedure according to Commission Regulation (EC) No
1234/2008

5.2.1. Tookad - padeliporfin - EMEA/H/C/004182/II/0013

STEBA Biotech S.A

Rapporteur: Bruno Sepodes, PRAC Rapporteur: Maia Uusküla

Scope: “Modification of the wording of the existing indication. The new wording will be the
treatment of adult patients with previously untreated, unilateral, low-risk, adenocarcinoma
of the prostate with a life expectancy ≥ 10 years and Clinical stage T1c or T2a, ISUP Grade
Group ≤ 2, based on high-resolution biopsy strategies, PSA ≤ 10 ng/mL, Low core positivity
for Tookad; as a consequence, section 4.1 of the SmPC is updated. Version 6.0 of the RMP
has also been submitted.”

Letter from the applicant dated 18 October 2021 requesting an extension to the clock stop
to respond to the request for supplementary information adopted in September 2021.

Action: For adoption

Request for Supplementary Information adopted on 16.09.2021, 20.05.2021.

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5.2.2. Keytruda - pembrolizumab - EMEA/H/C/003820/II/0109

Merck Sharp & Dohme B.V.

Rapporteur: Armando Genazzani, Co-Rapporteur: Jan Mueller-Berghaus, PRAC Rapporteur:

Menno van der Elst

Scope: “Extension of indication for Keytruda as monotherapy in the treatment of

unresectable or metastatic MSI-H or dMMR colorectal, endometrial, gastric, small intestine,
biliary, or pancreatic cancer in adults who have received prior therapy. The proposed
indication is based on the results from the KEYNOTE-164 (KN164) and KEYNOTE-158
(KN158) trials. As a consequence, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated.
The Package Leaflet is updated in accordance. An updated version of the RMP (Version
34.1) has been submitted.”

Letter from the applicant requesting an extension to the clock stop to respond to the
request for supplementary information adopted in October 2021.

Action: For adoption

Request for Supplementary Information adopted on 14.10.2021.

5.3. Re-examination of Type II variation; variation of therapeutic

indication procedure according to Commission Regulation (EC) No
1234/2008

No items

6. Ancillary medicinal substances in medical devices

6.1. Ancillary medicinal substances in medical devices; Opinions/ Day

180 list of outstanding issues / Day 120 list of questions

No items

6.2. Update of Ancillary medicinal substances in medical devices

No items

7. Procedure under Article 83(1) of Regulation (EC) 726/2004

(Compassionate Use)

7.1. Procedure under Article 83(1) of Regulation (EC) 726/2004

(Compassionate Use)

No items

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8. Pre-submission issues

8.1. Pre-submission issue

8.1.1. etranacogene dezaparvovec - H0004827

Treatment of severe Haemophilia B

Scope: Briefing note and the Rapporteurs’ recommendation on the request for accelerated
assessment.

Action: For adoption

8.2. Priority Medicines (PRIME)

Information related to priority medicines cannot be released at present time as these

contain commercially confidential information

8.2.1. List of applications received

Action: For information

8.2.2. Recommendation for PRIME eligibility

Action: For adoption

9. Post-authorisation issues

9.1. Post-authorisation issues

9.1.1. Rubraca - rucaparib - EMEA/H/C/004272/II/0029

Clovis Oncology Ireland Limited

Rapporteur: Blanca Garcia-Ochoa, PRAC Rapporteur: Annika Folin

Scope: “Update of sections 4.4, 4.8 and 5.1 of the SmPC based on final results from study
CO-338-043 (ARIEL4); this is a phase 3, multicentre, open-label, randomised study
evaluating the efficacy and safety of rucaparib versus chemotherapy for treatment of
relapsed ovarian cancer listed as a specific obligation in the Annex II; the Package Leaflet is
updated accordingly. The RMP version 6.1 has also been submitted. With this variation
application, the MAH requests for the Rubraca marketing authorisation to no longer be
subject to specific obligations. The SmPC, Annex II and PL are updated accordingly. In
addition, the MAH took the opportunity to make minor editorial changes and bring the PI in
line with the latest QRD template version 10.2 Rev.1.”

Action: For adoption

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9.1.2. Ad-hoc assessment of the therapeutic effect of monoethyl fumarate salts within
Fumaderm

Implementation of the Judgment of the General Court of 5 May 2021 in Case T-611/18,
Pharmaceutical Works Polpharma v EMA; Annulment of EMA’s non-validation decision for a
generic application of Tecfidera.

For the purpose of the implementation of the Judgment, the CHMP is assessing the
therapeutic contribution of monoethyl fumarate (MEF) salts within the combination product
Fumaderm.

Scope: Opinion

Action: For adoption

9.1.3. Piqray - alpelisib - EMEA/H/C/004804/II/0008/G

Novartis Europharm Limited

Rapporteur: Blanca Garcia-Ochoa, PRAC Rapporteur: Menno van der Elst

Scope: “Update of section 5.1 of the SmPC based on final results from study CBYL719C2301
(SOLAR-1) listed as a PAES in the Annex II; this is a phase III, randomized, double-blind,
placebo controlled study of alpelisib in combination with fulvestrant for men and
postmenopausal women with hormone receptor positive, HER2-negative advanced breast
cancer which progressed on or after aromatase inhibitor treatment; the Annex II is updated
accordingly. In addition, the MAH is updating the ATC code in the SmPC. The RMP version
5.0 has also been submitted.”

Action: For adoption

9.1.4. Ocaliva – obeticholic acid – EMEA/H/C/004093/R/0027

Intercept Pharma International Limited

Rapporteur: Blanca Garcia-Ochoa, PRAC Rapporteur: Liana Gross-Martirosyan

Scope: Renewal of conditional marketing authorisation

Action: For adoption

Request for Supplementary Information adopted on 16.09.2021.

9.1.5. Cervarix - human papillomavirus vaccine [types 16, 18] (recombinant, adjuvanted,
adsorbed) - EMEA/H/C/000721/II/0110

GlaxoSmithkline Biologicals SA

Rapporteur: Christophe Focke, Co-Rapporteur: Jan Mueller-Berghaus, PRAC Rapporteur:

Jean-Michel Dogné

Scope: “Extension of indication to include the prevention of head and neck cancers causally
related to certain oncogenic human papillomavirus types for Cervarix; as a consequence,
sections 4.1 and 5.1 of the SmPC are updated. The Package Leaflet is updated in
accordance. Version 23.0 of the RMP has also been submitted to mainly reflect the updated
indication. In addition, the Marketing authorisation holder (MAH) took the opportunity to

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 update the list of local representatives in the Package Leaflet. Furthermore, the PI is
brought in line with the latest QRD template version 10.1.”

Withdrawal of extension of indication application

Action: For information

Request for Supplementary Information adopted on 20.05.2021, 17.09.2020.

9.1.6. Leganto – Rotigotine – EMA/H/C/002380

UCB Pharma S.A.

Rapporteur: Bruno Sepodes Co-Rapporteur : Hans Lodewijk Hillege

Scope: Withdrawal of marketing authorisation

Action: For information

9.1.7. Nulojix - belatacept - EMEA/H/C/002098/II/0065/G

Bristol-Myers Squibb Pharma EEIG

Rapporteur: Filip Josephson

Scope: quality variation

Action: For adoption

Request for Supplementary Information adopted on 14.10.2021, 25.03.2021, 12.11.2020,

12.03.2020.

9.1.8. Kanuma - sebelipase alfa – Orphan – EMEA/H/C/004004/II/0032

Alexion Europe SAS

Rapporteur: Karin Janssen van Doorn

Scope: “Update of section 4.2 of the SmPC in order to introduce a new posology regimen
(higher starting dose of 3 mg/kg once weekly) based on cumulative data from clinical
studies and real-world clinical practice for patients with Rapidly Progressive LAL deficiency
presenting within the first six months of life. Consequently, the dosing information for
patients with Rapidly Progressive LAL deficiency and paediatric and adult patients with LAL
deficiency is modified. In addition, editorial update is made in sections 4.8, 5.1, 5.2 and 6.6
following the new posology regimen. The Package Leaflet is updated accordingly.”

Action: For adoption

Request for Supplementary Information adopted on 16.09.2021.

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10. Referral procedures

10.1. Procedure for Centrally Authorised products under Article 20 of

Regulation (EC) No 726/2004

No items

10.2. Requests for CHMP Opinion under Article 5(3) of Regulation (EC) No
726/2004

No items

10.3. Procedure under Articles 5(2) and 10 of Regulation (EC) No

726/2004

No items

10.4. Disagreement between Member States on application for medicinal

product (potential serious risk to public health) –under Article 29(4)
of Directive 2001/83/EC

No items

10.5. Harmonisation - Referral procedure under Article 30 of Directive

2001/83/EC

No items

10.6. Community Interests - Referral under Article 31 of Directive

2001/83/EC

No items

10.7. Re-examination Procedure under Article 32(4) of Directive

2001/83/EC

No items

10.8. Procedure under Article 107(2) of Directive 2001/83/EC

No items

10.9. Disagreement between Member States on Type II variation–

Arbitration procedure initiated by MAH under Article 6(13) of
Commission Regulation (EC) No 1084/2003

No items

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10.10. Procedure under Article 29 of Regulation (EC) 1901/2006

No items

10.11. Referral under Article 13 Disagreement between Member States on

Type II variation– Arbitration procedure initiated by Member State
under Article 13 (EC) of Commission Regulation No 1234/2008

No items

11. Pharmacovigilance issue

11.1. Early Notification System

November 2021 Early Notification System on envisaged CHMP/CMDh outcome accompanied

by communication to the general public.

Action: For information

12. Inspections

12.1. GMP inspections

Information related to GMP inspections will not be published as it undermines the purpose
of such inspections

12.2. GCP inspections

Information related to GCP inspections will not be published as it undermines the purpose of
such inspections

12.3. Pharmacovigilance inspections

Information related to Pharmacovigilance inspections will not be published as it undermines

the purpose of such inspections

12.4. GLP inspections

Information related to GLP inspections will not be published as it undermines the purpose of
such inspections

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13. Innovation Task Force

13.1. Minutes of Innovation Task Force

No items

13.2. Innovation Task Force briefing meetings

No items

13.3. Requests for CHMP Opinion under Article 57(1)J and (1)P of
Regulation (EC) No 726/2004

No items

13.4. Nanomedicines activities

No items

14. Organisational, regulatory and methodological matters

14.1. Mandate and organisation of the CHMP

14.1.1. Roles and responsibilities of CHMP members

Refresher course on the roles and responsibilities of Committee members

Action: For information

14.2. Coordination with EMA Scientific Committees

14.2.1. Pharmacovigilance Risk Assessment Committee (PRAC)

List of Union Reference Dates and frequency of submission of Periodic Safety Update
Reports (EURD list) for November 2021

Action: For adoption

14.2.2. Paediatric Committee (PDCO)

PIPs reaching D30 at October 2021 PDCO

Action: For information

Report from the PDCO meeting held on 12-15 October 2021

Action: For information

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14.3. Coordination with EMA Working Parties/Working Groups/Drafting
Groups

14.3.1. Safety Working Party (SWP)

Chair: Susanne Brendler-Schwaab

Response from SWP to CMDh questions on the acceptable intake for nitrosamine N-
Nitrosodi-n-propylamine (NDPA)

Action: for adoption

14.3.2. Biologics Working Party (BWP)

Chair: Sol Ruiz/Nanna Aaby Kruse

Reports from BWP November 2021 meeting to CHMP for adoption:

- 22 reports on products in scientific advice and protocol assistance

- 21 reports on products in pre-authorisation procedures

- 8 reports on products in plasma master file

Action: For adoption

14.3.3. Scientific Advice Working Party (SAWP)

Chair: Anja Schiel

Report from the SAWP meeting held on 25-28 October 2021. Table of conclusions

Action: For information

Scientific advice letters:

Information related to scientific advice letters cannot be released at present time as these
contain commercially confidential information.

14.4. Cooperation within the EU regulatory network

14.4.1. Nitrosamines Multidisciplinary Expert Group (NMEG) on rifampicin

Scope: Report from NMEG and advice to CMDh

Action: For adoption

14.5. Cooperation with International Regulators

No items

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14.6. Contacts of the CHMP with external parties and interaction with the
Interested Parties to the Committee

No items

14.7. CHMP work plan

No items

14.8. Planning and reporting

No items

14.9. Others

No items

15. Any other business

15.1. AOB topic

15.1.1. Update on COVID-19

Action: For information

15.1.2. Sotrovimab - EMEA/H/0005676

Treatment of coronavirus disease 2019 (COVID-19)

Scope: interim opinion on 4th rolling review

Action: For adoption

15.1.3. COVID-19 vaccine - EMEA/H/C/005754

Active immunisation to prevent COVID-19 caused by SARS-CoV-2, in individuals 18 years of

age and older.

Scope: interim opinion on 2nd rolling review

Action: For adoption

15.1.4. COVID-19 vaccine (NVX-CoV2373) – EMEA/H/C/005808

prevention of COVID-19

Scope: Update on rolling review

Action: For information

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 Explanatory notes

The notes below give a brief explanation of the main sections and headings in the CHMP agenda and
should be read in conjunction with the agenda or the minutes.

Oral explanations (section 2)

The items listed in this section are those for which marketing authorisation holders (MAHs) or
applicants have been invited to the CHMP plenary meeting to address questions raised by the
Committee. Oral explanations normally relate to on-going applications (section 3, 4 and 5) or referral
procedures (section 10) but can relate to any other issue for which the CHMP would like to discuss with
company representatives in person.

Initial applications (section 3)

This section lists applications for marketing authorisations of new medicines that are to be discussed
by the Committee.

Section 3.1 is for medicinal products nearing the end of the evaluation and for which the CHMP is
expected to adopt an opinion at this meeting on whether marketing authorisation should be granted.
Once adopted, the CHMP opinion will be forwarded to the European Commission for a final legally
binding decision valid throughout the EU.

The other items in the section are listed depending on the stage of the evaluation, which is shown
graphically below:

The assessment of an application for a new medicine takes up to 210 ‘active’ days. This active
evaluation time is interrupted by at least one ‘clock-stop’ during which time the applicant prepares the
answers to questions from the CHMP. The clock stop happens after day 120 and may also happen after
day 180, when the CHMP has adopted a list of questions or outstanding issues to be addressed by the
company. Related discussions are listed in the agenda under sections 3.2 (Day 180 List of
outstanding issues) and 3.3 (Day 120 list of questions).

CHMP discussions may also occur at any other stage of the evaluation, and these are listed under
section 3.4, update on ongoing new applications for centralised procedures.

The assessment leads to an opinion from the CHMP by day 210. Following a CHMP opinion the
European Commission takes usually 67 days to issue a legally binding decision (i.e. by day 277 of the
procedure). CHMP discussions on products that have received a CHMP opinion and are awaiting a
decision are listed under section 3.6, products in the decision making phase.

Extension of marketing authorisations according to Annex I of Reg. 1234/2008 (section 4)

Extensions of marketing authorisations are applications for the change or addition of new strengths,

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formulations or routes of administration to existing marketing authorisations. Extension applications
follow a 210-day evaluation process, similarly to applications for new medicines (see figure above).

Type II variations - Extension of indication procedures (section 5)

Type II variations are applications for a change to the marketing authorisation which requires an
update of the product information and which is not covered in section 4. Type II variations include
applications for a new use of the medicine (extension of indication), for which the assessment takes up
to 90 days. For the applications listed in this section, the CHMP may adopt an opinion or request
supplementary information from the applicant.

Ancillary medicinal substances in medical devices (section 6)

Although the EMA does not regulate medical devices it can be asked by the relevant authorities (the
so-called Notified Bodies) that are responsible for regulating these devices to give a scientific opinion
on a medicinal substance contained in a medical device.

Re-examination procedures (new applications) under article 9(2) of regulation no 726/2004

(section 3.5)

This section lists applications for new marketing authorisation for which the applicant has requested a
re-examination of the opinion previously issued by the CHMP.

Re-examination procedures (section5.3)

This section lists applications for type II variations (including extension of indication applications) for
which the applicant has requested re-examination of the opinion previously issued by the CHMP.

Withdrawal of application (section 3.7)

Applicants may decide to withdraw applications at any stage during the assessment and a CHMP
opinion will therefore not be issued. Withdrawals are included in the agenda for information or
discussion, as necessary.

Procedure under article 83(1) of regulation (EC) 726/2004 (compassionate use) (section 7)

Compassionate use is a way of making available to patients with an unmet medical need a promising
medicine which has not yet been authorised (licensed) for their condition. Upon request, the CHMP
provides recommendations to all EU Member States on how to administer, distribute and use certain
medicines for compassionate use.

Pre-submission issues (section 8)

In some cases the CHMP may discuss a medicine before a formal application for marketing
authorisation is submitted. These cases generally refer to requests for an accelerated assessment for
medicines that are of major interest for public health or can be considered a therapeutic innovation. In
case of an accelerated assessment the assessment timetable is reduced from 210 to 150 days.

Post-authorisation issues (section 9)

This section lists other issues concerning authorised medicines that are not covered elsewhere in the
agenda. Issues include supply shortages, quality defects, some annual reassessments or renewals or
type II variations to marketing authorisations that would require specific discussion at the plenary.

Referral procedures (section 10)

This section lists referrals that are ongoing or due to be started at the plenary meeting. A referral is a
procedure used to resolve issues such as concerns over the safety or benefit-risk balance of a medicine
or a class of medicines. In a referral, the EMA is requested to conduct a scientific assessment of a

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particular medicine or class of medicines on behalf of the EU. Further information on such procedures
can be found here.

Pharmacovigilance issues (section 11)

This section lists issues that have been discussed at the previous meeting of the PRAC, the EMA’s
committee responsible for evaluating and monitoring safety issues for medicines. Feedback is provided
by the PRAC. This section also refers to the early notification system, a system used to notify the
European regulatory network on proposed EMA communication on safety of medicines.

Inspections Issues (section 12)

This section lists inspections that are undertaken for some medicinal products. Inspections are carried
out by regulatory agencies to ensure that marketing authorisation holders comply with their
obligations. Inspection can relate to good manufacturing practice (GMP), good clinical practice (GCP),
good laboratory practice (GLP) or good pharmacovigilance practice (GVP).

Innovation task force (section 13)

The Innovation Task Force (ITF) is a body set up to encourage early dialogue with applicants
developing innovative medicines. Minutes from the last ITF meeting as well as any related issue that
requires discussion with the CHMP are listed in this section of the agenda. Further information on the
ITF can be found here.

Scientific advice working party (SAWP) (section 14.3.1)

This section refers to the monthly report from the CHMP’s Scientific Advice Working Party (SAWP) on
scientific advice given to companies during the development of medicines. Further general information
on SAWP can be found here.

Satellite groups / other committees (section 14.2)

This section refers to the reports from groups and committees making decisions relating to human
medicines: the Coordination Group for Mutual Recognition and Decentralised Procedures – Human
(CMDh), the Committee for Orphan Medicinal Products (COMP), the Committee for Herbal Medicinal
Products (HMPC), Paediatric Committee (PDCO), the Committee for Advanced Therapies (CAT) and the
Pharmamacovigilance Risk Assessment Committee (PRAC).

Invented name issues (section 14.3)

This section list issues related to invented names proposed by applicants for new medicines. The CHMP
has established the Name Review Group (NRG) to perform reviews of the invented names. The group's
main role is to consider whether the proposed names could create a public-health concern or potential
safety risk. Further information can be found here.

More detailed information on the above terms can be found on the EMA website: www.ema.europa.eu/

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 08 November 2021
EMA/CHMP/625004/2021

Annex to 08-11 November 2021 CHMP Agenda

Pre-submission and post-authorisations issues

A. PRE-SUBMISSION ISSUES ..................................................................... 3

A.1. ELIGIBILITY REQUESTS ....................................................................................... 3
A.2. Appointment of Rapporteur / Co-Rapporteur Full Applications .................................. 3
A.3. PRE-SUBMISSION ISSUES FOR INFORMATION ....................................................... 3

B. POST-AUTHORISATION PROCEDURES OUTCOMES ................................. 3

B.1. Annual re-assessment outcomes .......................................................................... 3
B.1.1. Annual reassessment for products authorised under exceptional circumstances ....... 3
B.2. RENEWALS OF MARKETING AUTHORISATIONS OUTCOMES ...................................... 4
B.2.1. Renewals of Marketing Authorisations requiring 2nd Renewal ................................ 4
B.2.2. Renewals of Marketing Authorisations for unlimited validity................................... 4
B.2.3. Renewals of Conditional Marketing Authorisations ................................................ 5
B.3. POST-AUTHORISATION PHARMACOVIGILANCE OUTCOMES...................................... 6
B.4. EPARs / WPARs .................................................................................................. 8
B.5. TYPE II VARIATION, WORKSHARING PROCEDURE OUTCOMES ................................. 9
B.5.1. CHMP assessed procedures scope: Pharmaceutical aspects ................................... 9
B.5.2. CHMP assessed procedures scope: Non-Clinical and Clinical aspects ..................... 15
B.5.3. CHMP-PRAC assessed procedures .................................................................... 29
B.5.4. PRAC assessed procedures .............................................................................. 36
B.5.5. CHMP-CAT assessed procedures ...................................................................... 44
B.5.6. CHMP-PRAC-CAT assessed procedures ............................................................. 45
B.5.7. PRAC assessed ATMP procedures ..................................................................... 45
B.5.8. Unclassified procedures and worksharing procedures of type I variations .............. 45
B.5.9. Information on withdrawn type II variation / WS procedure ................................ 48
B.5.10. Information on type II variation / WS procedure with revised timetable .............. 48
B.6. START OF THE PROCEDURES TIMETABLES FOR INFORMATION .............................. 48
B.6.1. Start of procedure for New Applications: timetables for information ..................... 48
B.6.2. Start of procedure for Extension application according to Annex I of Reg.
1234/2008): timetables for information ..................................................................... 49

Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands

Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us
Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union

© European Medicines Agency, 2021. Reproduction is authorised provided the source is acknowledged.
B.6.3. Restart of procedure - responses received to Day 120 List of Questions timetables:
for information ........................................................................................................ 50
B.6.4. Annual Re-assessments: timetables for adoption ............................................... 51
B.6.5. Renewals of Marketing Authorisations: timetables for adoption provided only if the
validation has been completed .................................................................................. 51
B.6.6. VARIATIONS – START OF THE PROCEDURE ....................................................... 53
B.6.7. Type II Variations scope of the Variations: Extension of indication ....................... 53
B.6.8. CHMP assessed procedures scope: Pharmaceutical aspects ................................ 56
B.6.9. CHMP assessed procedures scope: Non-Clinical and Clinical aspects ..................... 58
B.6.10. CHMP-PRAC assessed procedures................................................................... 62
B.6.11. PRAC assessed procedures ............................................................................ 64
B.6.12. CHMP-CAT assessed procedures .................................................................... 64
B.6.13. CHMP-PRAC-CAT assessed procedures ............................................................ 64
B.6.14. PRAC assessed ATMP procedures ................................................................... 65
B.6.15. Unclassified procedures and worksharing procedures of type I variations ............ 65
B.7. DOCUMENTS TABLED IN MMD AFTER THE CHMP PLENARY ..................................... 66
B.7.1. Yearly Line listing for Type I and II variations .................................................... 66
B.7.2. Monthly Line listing for Type I variations ........................................................... 66
B.7.3. Opinion on Marketing Authorisation transfer (MMD only) .................................... 66
B.7.4. Notifications in accordance with Article 61(3) of Council Directive 2001/83/EC (MMD
only) ..................................................................................................................... 66
B.7.5. Request for supplementary information relating to Notification of Type I variation
(MMD only) ............................................................................................................ 66
B.7.6. Notifications of Type I Variations (MMD only) .................................................... 66

C. Annex C - Post-Authorisation Measures (PAMs), (Line listing of Post

authorisation measures with a description of the PAM. Procedures starting
in that given month with assessment timetabled) ................................... 66

D. Annex D - Post-Authorisation Measures (PAMs), (Details on PAMs

including description and conclusion, for adoption by CHMP in that given
month, or finalised ones with PRAC recommendation and no adoption by
CHMP needed) ......................................................................................... 66

E. Annex E - EMA CERTIFICATION OF PLASMA MASTER FILES ................. 66

E.1. Timetables – starting & ongoing procedures: For information ................................. 66

F. ANNEX F - Decision of the Granting of a Fee Reduction/Fee Waiver .... 66

G. ANNEX G .............................................................................................. 66
G.1. Final Scientific Advice (Reports and Scientific Advice letters): ................................ 66
G.1.1. List of procedures concluding at 08-11 November 2021 CHMP plenary: ................ 67
G.1.2. List of procedures starting in November 2021 for December 2021 CHMP adoption of
outcomes ............................................................................................................... 67

H. ANNEX H - Product Shared Mailboxes – e-mail address ....................... 67

EMA/CHMP/625004/2021 Page 2/67

A. PRE-SUBMISSION ISSUES

A.1. ELIGIBILITY REQUESTS

Report on Eligibility to Centralised Procedure for

November 2021: For adoption

A.2. Appointment of Rapporteur / Co-Rapporteur Full Applications

Final Outcome of Rapporteurship allocation for

November 2021: For adoption

A.3. PRE-SUBMISSION ISSUES FOR INFORMATION

Information related to pre-submission of initial applications cannot be released at the present time
as these contain commercially confidential information.

B. POST-AUTHORISATION PROCEDURES OUTCOMES

B.1. Annual re-assessment outcomes

B.1.1. Annual reassessment for products authorised under exceptional circumstances

Atriance - nelarabine -
EMEA/H/C/000752/S/0055
Novartis Europharm Limited, Rapporteur: Sinan
B. Sarac, PRAC Rapporteur: Anette Kirstine
Stark

IMVANEX - smallpox vaccine (live modified

vaccinia virus Ankara) -
EMEA/H/C/002596/S/0069
Bavarian Nordic A/S, Rapporteur: Jan Mueller-
Berghaus, PRAC Rapporteur: Brigitte Keller-
Stanislawski

Mepsevii - vestronidase alfa -

EMEA/H/C/004438/S/0025, Orphan
Ultragenyx Germany GmbH, Rapporteur:
Johann Lodewijk Hillege, PRAC Rapporteur: Eva
A. Segovia

Naglazyme - galsulfase -
EMEA/H/C/000640/S/0087
BioMarin International Limited, Rapporteur:
Fátima Ventura, PRAC Rapporteur: Ana Sofia
Diniz Martins

EMA/CHMP/625004/2021 Page 3/67

B.2. RENEWALS OF MARKETING AUTHORISATIONS OUTCOMES

B.2.1. Renewals of Marketing Authorisations requiring 2nd Renewal

elmiron - pentosan polysulfate sodium -

EMEA/H/C/004246/R/0024
bene-Arzneimittel GmbH, Rapporteur: Jean-
Michel Race, Co-Rapporteur: Romaldas
Mačiulaitis, PRAC Rapporteur: Ana Sofia Diniz
Martins

Yargesa - miglustat -
EMEA/H/C/004016/R/0011
Piramal Critical Care B.V., Generic, Generic of
Zavesca, Rapporteur: Daniela Philadelphy, PRAC
Rapporteur: Ulla Wändel Liminga
Request for Supplementary Information adopted
on 16.09.2021.

B.2.2. Renewals of Marketing Authorisations for unlimited validity

Brineura - cerliponase alfa -

EMEA/H/C/004065/R/0034, Orphan
BioMarin International Limited, Rapporteur:
Martina Weise, Co-Rapporteur: Maria
Concepcion Prieto Yerro, PRAC Rapporteur: Ulla
Wändel Liminga

Darzalex - daratumumab -
EMEA/H/C/004077/R/0054, Orphan
Janssen-Cilag International NV, Rapporteur:
Sinan B. Sarac, Co-Rapporteur: Blanca Garcia-
Ochoa, PRAC Rapporteur: Marcia Sofia Sanches
de Castro Lopes Silva

Emtricitabine/tenofovir disoproxil Krka

d.d. - emtricitabine / tenofovir disoproxil -
EMEA/H/C/004686/R/0017
KRKA, d.d., Novo mesto, Generic, Duplicate,
Duplicate of Emtricitabine/Tenofovir disoproxil
Krka, Rapporteur: John Joseph Borg, PRAC
Rapporteur: Ana Sofia Diniz Martins

Erelzi - etanercept -
EMEA/H/C/004192/R/0037
Sandoz GmbH, Rapporteur: Johann Lodewijk
Hillege, Co-Rapporteur: Outi Mäki-Ikola, PRAC
Rapporteur: Eva A. Segovia

LEDAGA - chlormethine -
EMEA/H/C/002826/R/0030, Orphan
Helsinn Birex Pharmaceuticals Limited,

EMA/CHMP/625004/2021 Page 4/67

Rapporteur: Sinan B. Sarac, PRAC Rapporteur:
Tiphaine Vaillant
Request for Supplementary Information adopted
on 16.09.2021.

Qarziba - dinutuximab beta -

EMEA/H/C/003918/R/0029, Orphan
EUSA Pharma (Netherlands) B.V., Rapporteur:
Paula Boudewina van Hennik, Co-Rapporteur:
Sinan B. Sarac, PRAC Rapporteur: Brigitte
Keller-Stanislawski

Refixia - nonacog beta pegol -

EMEA/H/C/004178/R/0025
Novo Nordisk A/S, Rapporteur: Andrea Laslop,
Co-Rapporteur: Alexandre Moreau, PRAC
Rapporteur: Brigitte Keller-Stanislawski

Rolufta Ellipta - umeclidinium -

EMEA/H/C/004654/R/0019
GlaxoSmithKline Trading Services Limited,
Rapporteur: Maria Concepcion Prieto Yerro, Co-
Rapporteur: Jayne Crowe, PRAC Rapporteur:
Ilaria Baldelli
Request for Supplementary Information adopted
on 16.09.2021.

Skilarence - dimethyl fumarate -

EMEA/H/C/002157/R/0030
Almirall S.A, Rapporteur: Janet Koenig, Co-
Rapporteur: Kristina Dunder, PRAC Rapporteur:
Annika Folin

Spinraza - nusinersen -
EMEA/H/C/004312/R/0025, Orphan
Biogen Netherlands B.V., Rapporteur: Bruno
Sepodes, Co-Rapporteur: Johann Lodewijk
Hillege, PRAC Rapporteur: Ulla Wändel Liminga

TAGRISSO - osimertinib -
EMEA/H/C/004124/R/0044
AstraZeneca AB, Rapporteur: Blanca Garcia-
Ochoa, PRAC Rapporteur: Menno van der Elst

B.2.3. Renewals of Conditional Marketing Authorisations

Caprelsa - vandetanib -
EMEA/H/C/002315/R/0050
Genzyme Europe BV, Rapporteur: Alexandre
Moreau, Co-Rapporteur: Paula Boudewina van
Hennik, PRAC Rapporteur: Tiphaine Vaillant

EMA/CHMP/625004/2021 Page 5/67

OCALIVA - obeticholic acid - See 9.1
EMEA/H/C/004093/R/0027, Orphan
Intercept Pharma International Limited,
Rapporteur: Blanca Garcia-Ochoa, PRAC
Rapporteur: Liana Gross-Martirosyan
Request for Supplementary Information adopted
on 16.09.2021.

SIRTURO - bedaquiline -
EMEA/H/C/002614/R/0045, Orphan
Janssen-Cilag International NV, Rapporteur:
Filip Josephson, PRAC Rapporteur: Ulla Wändel
Liminga

B.3. POST-AUTHORISATION PHARMACOVIGILANCE OUTCOMES

Signal detection

PRAC recommendations on signals adopted at

the PRAC meeting held on 25-28 October 2021
PRAC:

Signal of Toxic Encephalopathy in

patients with renal impairment

Invanz – Ertapenem

Rapporteur: Fatima Ventura, Co-Rapporteur:

Ondřej Slanař, PRAC Rapporteur: Ana Sofia
Diniz Martins
PRAC recommendation on a variation
Action: For adoption
Signal of colitis

Kisplyx, Lenvima – Lenvatinib

Rapporteur: Karin Janssen van Doorn, PRAC

Rapporteur: Annika Folin
PRAC recommendation on a variation
Action: For adoption
PSUR procedures for which PRAC adopted a
recommendation for variation of the terms of
the MA at its November 2021 meeting:

EMEA/H/C/PSUSA/00000413/202103
(bimatoprost)
CAPS:
Lumigan (EMEA/H/C/000391) (bimatoprost),
Allergan Pharmaceuticals Ireland, Rapporteur:
Sinan B. Sarac
NAPS:
NAPs - EU
PRAC Rapporteur: Anette Kirstine Stark,
“07/03/2018 To: 07/03/2021”

EMA/CHMP/625004/2021 Page 6/67

EMEA/H/C/PSUSA/00003127/202102
(voriconazole)
CAPS:
Vfend (EMEA/H/C/000387) (voriconazole),
Pfizer Europe MA EEIG, Rapporteur: Johann
Lodewijk Hillege
NAPS:
NAPs - EU
PRAC Rapporteur: Liana Gross-Martirosyan,
“01/03/2018 To: 28/02/2021”

EMEA/H/C/PSUSA/00009200/202103
(ipilimumab)
CAPS:
Yervoy (EMEA/H/C/002213) (ipilimumab),
Bristol-Myers Squibb Pharma EEIG, Rapporteur:
Paula Boudewina van Hennik, PRAC Rapporteur:
Menno van der Elst, “25/03/2020 To:
24/03/2021”

EMEA/H/C/PSUSA/00009327/202104
(vandetanib)
CAPS:
Caprelsa (EMEA/H/C/002315) (vandetanib),
Genzyme Europe BV, Rapporteur: Alexandre
Moreau, PRAC Rapporteur: Tiphaine Vaillant,
“06/04/2020 To: 06/04/2021”

EMEA/H/C/PSUSA/00010143/202103
(dimethyl fumarate (multiple sclerosis))
CAPS:
TECFIDERA (EMEA/H/C/002601) (dimethyl
fumarate), Biogen Netherlands B.V.,
Rapporteur: Martina Weise, PRAC Rapporteur:
Martin Huber, “26/03/2019 To: 26/03/2021”

EMEA/H/C/PSUSA/00010635/202103
(avelumab)
CAPS:
Bavencio (EMEA/H/C/004338) (avelumab),
Merck Europe B.V., Rapporteur: Filip Josephson,
PRAC Rapporteur: Anette Kirstine Stark,
“23/09/2020 To: 22/03/2021”

EMEA/H/C/PSUSA/00010645/202103
(dupilumab)
CAPS:
Dupixent (EMEA/H/C/004390) (dupilumab),
sanofi-aventis groupe, Rapporteur: Jan Mueller-
Berghaus, PRAC Rapporteur: Kimmo Jaakkola,
“28/03/2020 To: 28/03/2021”

EMEA/H/C/PSUSA/00010780/202103

EMA/CHMP/625004/2021 Page 7/67

(cemiplimab)
CAPS:
LIBTAYO (EMEA/H/C/004844) (cemiplimab),
Regeneron Ireland Designated Activity Company
(DAC), Rapporteur: Sinan B. Sarac, PRAC
Rapporteur: Menno van der Elst, “27/03/2020
To: 27/03/2021”

EMEA/H/C/PSUSA/00010833/202104
(enoxaparin)
CAPS:
Inhixa (EMEA/H/C/004264) (enoxaparin
sodium), Techdow Pharma Netherlands B.V.,
Rapporteur: Andrea Laslop
NAPS:
NAPs - EU
PRAC Rapporteur: Menno van der Elst,
“03/04/2020 To: 03/04/2021”

B.4. EPARs / WPARs

ASPAVELI - pegcetacoplan - For information only. Comments can be sent to

EMEA/H/C/005553, Orphan the PL in case necessary.
Swedish Orphan Biovitrum AB (publ),
paroxysmal nocturnal haemoglobinuria (PNH),
New active substance (Article 8(3) of Directive
No 2001/83/EC)

Cibinqo - abrocitinib - EMEA/H/C/005452 For information only. Comments can be sent to

Pfizer Europe MA EEIG, Indicated for the the PL in case necessary.
treatment of moderate-to-severe atopic
dermatitis in adults and adolescents 12 years
and older who are candidates for systemic
therapy., New active substance (Article 8(3) of
Directive No 2001/83/EC)

RYBREVANT - amivantamab - For information only. Comments can be sent to

EMEA/H/C/005454 the PL in case necessary.
Janssen-Cilag International N.V., for treatment
of adult patients with locally advanced or
metastatic non-small cell lung cancer (NSCLC)
with activating epidermal growth factor receptor
(EGFR) Exon 20 insertion mutations, after
failure of platinum-based chemotherapy., New
active substance (Article 8(3) of Directive No
2001/83/EC)

Sitagliptin SUN - sitagliptin fumarate - For information only. Comments can be sent to
EMEA/H/C/005741 the PL in case necessary.
Sun Pharmaceutical Industries Europe B.V.,
treatment of type 2 diabetes mellitus, Generic,
Generic of Januvia, Generic application (Article

EMA/CHMP/625004/2021 Page 8/67

10(1) of Directive No 2001/83/EC)

TRODELVY - sacituzumab govitecan - For information only. Comments can be sent to

EMEA/H/C/005182 the PL in case necessary.
Gilead Sciences Ireland UC, treatment of
unresectable locally advanced or metastatic
triple-negative breast cancer (mTNBC), New
active substance (Article 8(3) of Directive No
2001/83/EC)

Vaxneuvance - pneumococcal For information only. Comments can be sent to

polysaccharide conjugate vaccine the PL in case necessary.
(adsorbed) - EMEA/H/C/005477
Merck Sharp & Dohme B.V., immunisation for
the prevention of invasive disease and
pneumonia caused by Streptococcus
pneumoniae. Pneumonia caused by
Streptococcus pneumoniae, New active
substance (Article 8(3) of Directive No
2001/83/EC)

B.5. TYPE II VARIATION, WORKSHARING PROCEDURE OUTCOMES

Scopes related to Chemistry, Manufacturing, and Controls cannot be released at the present time
as these contain commercially confidential information.

B.5.1. CHMP assessed procedures scope: Pharmaceutical aspects

Abevmy - bevacizumab -
EMEA/H/C/005327/II/0005/G
Mylan IRE Healthcare Limited, Rapporteur: Jan
Mueller-Berghaus

Adakveo - crizanlizumab - Positive Opinion adopted by consensus on

EMEA/H/C/004874/II/0005, Orphan 21.10.2021. The Icelandic and Norwegian CHMP
Novartis Europharm Limited, Rapporteur: Members were in agreement with the CHMP
Daniela Philadelphy recommendation.
Opinion adopted on 21.10.2021.

ADYNOVI - rurioctocog alfa pegol -

EMEA/H/C/004195/II/0022/G
Baxalta Innovations GmbH, Rapporteur: Andrea
Laslop
Request for Supplementary Information adopted
on 16.09.2021.

Aimovig - erenumab - Positive Opinion adopted by consensus on

EMEA/H/C/004447/II/0017 21.10.2021. The Icelandic and Norwegian CHMP
Novartis Europharm Limited, Rapporteur: Members were in agreement with the CHMP
Kristina Dunder recommendation.
Opinion adopted on 21.10.2021.
Request for Supplementary Information adopted

EMA/CHMP/625004/2021 Page 9/67

on 02.09.2021.

Aranesp - darbepoetin alfa - Positive Opinion adopted by consensus on

EMEA/H/C/000332/II/0156 28.10.2021. The Icelandic and Norwegian CHMP
Amgen Europe B.V., Rapporteur: Martina Weise Members were in agreement with the CHMP
Opinion adopted on 28.10.2021. recommendation.

Aybintio - bevacizumab - Positive Opinion adopted by consensus on

EMEA/H/C/005106/II/0009 28.10.2021. The Icelandic and Norwegian CHMP
Samsung Bioepis NL B.V., Rapporteur: Andrea Members were in agreement with the CHMP
Laslop recommendation.
Opinion adopted on 28.10.2021.
Request for Supplementary Information adopted
on 02.09.2021.

Bylvay - odevixibat -
EMEA/H/C/004691/II/0001, Orphan
Albireo, Rapporteur: Johann Lodewijk Hillege

Cayston - aztreonam -
EMEA/H/C/000996/II/0084
Gilead Sciences Ireland UC, Rapporteur: Johann
Lodewijk Hillege

Ceprotin - human protein C - Request for supplementary information adopted

EMEA/H/C/000334/II/0124/G with a specific timetable.
Takeda Manufacturing Austria AG, Rapporteur:
Jan Mueller-Berghaus
Request for Supplementary Information adopted
on 21.10.2021.

Cinryze - human c1-esterase inhibitor - Request for supplementary information adopted

EMEA/H/C/001207/II/0089 with a specific timetable.
Shire Services BVBA, Rapporteur: Jan Mueller-
Berghaus
Request for Supplementary Information adopted
on 28.10.2021.

COMIRNATY - tozinameran - Positive Opinion adopted by consensus on

EMEA/H/C/005735/II/0069/G 28.10.2021. The Icelandic and Norwegian CHMP
BioNTech Manufacturing GmbH, Rapporteur: Members were in agreement with the CHMP
Filip Josephson recommendation.
Opinion adopted on 28.10.2021.

COMIRNATY - tozinameran -
EMEA/H/C/005735/II/0075/G
BioNTech Manufacturing GmbH, Rapporteur:
Filip Josephson

COMIRNATY - tozinameran - Positive Opinion adopted by consensus on

EMEA/H/C/005735/II/0078/G 29.10.2021. The Icelandic and Norwegian CHMP
BioNTech Manufacturing GmbH, Rapporteur: Members were in agreement with the CHMP
Filip Josephson recommendation.
Opinion adopted on 29.10.2021.

EMA/CHMP/625004/2021 Page 10/67

COVID-19 Vaccine Janssen - adenovirus Positive Opinion adopted by consensus on
type 26 encoding the SARS-CoV-2 spike 21.10.2021. The Icelandic and Norwegian CHMP
glycoprotein - EMEA/H/C/005737/II/0017 Members were in agreement with the CHMP
Janssen-Cilag International N.V., Rapporteur: recommendation.
Christophe Focke
Opinion adopted on 21.10.2021.

Drovelis - drospirenone / estetrol -

EMEA/H/C/005336/II/0003
Chemical Works of Gedeon Richter Plc. (Gedeon
Richter Plc.), Rapporteur: Kristina Dunder
Request for Supplementary Information adopted
on 23.09.2021.

Enhertu - trastuzumab deruxtecan - Request for supplementary information adopted

EMEA/H/C/005124/II/0009 with a specific timetable.
Daiichi Sankyo Europe GmbH, Rapporteur:
Sinan B. Sarac
Request for Supplementary Information adopted
on 28.10.2021.

Enhertu - trastuzumab deruxtecan - Request for supplementary information adopted

EMEA/H/C/005124/II/0010 with a specific timetable.
Daiichi Sankyo Europe GmbH, Rapporteur:
Sinan B. Sarac
Request for Supplementary Information adopted
on 28.10.2021.

Entyvio - vedolizumab - Request for supplementary information adopted

EMEA/H/C/002782/II/0063/G with a specific timetable.
Takeda Pharma A/S, Rapporteur: Armando
Genazzani
Request for Supplementary Information adopted
on 28.10.2021.

Eylea - aflibercept - Positive Opinion adopted by consensus on

EMEA/H/C/002392/II/0074 28.10.2021. The Icelandic and Norwegian CHMP
Bayer AG, Rapporteur: Alexandre Moreau Members were in agreement with the CHMP
Opinion adopted on 28.10.2021. recommendation.
Request for Supplementary Information adopted
on 02.09.2021.

Herceptin - trastuzumab - Positive Opinion adopted by consensus on

EMEA/H/C/000278/II/0173 28.10.2021. The Icelandic and Norwegian CHMP
Roche Registration GmbH, Rapporteur: Jan Members were in agreement with the CHMP
Mueller-Berghaus recommendation.
Opinion adopted on 28.10.2021.
Request for Supplementary Information adopted
on 09.09.2021.

Herzuma - trastuzumab - Request for supplementary information adopted

EMEA/H/C/002575/II/0041/G with a specific timetable.
Celltrion Healthcare Hungary Kft., Rapporteur:
Jan Mueller-Berghaus

EMA/CHMP/625004/2021 Page 11/67

Request for Supplementary Information adopted
on 21.10.2021.

IKERVIS - ciclosporin -
EMEA/H/C/002066/II/0026/G
Santen Oy, Rapporteur: Peter Kiely
Request for Supplementary Information adopted
on 22.07.2021.

Jakavi - ruxolitinib - Positive Opinion adopted by consensus on

EMEA/H/C/002464/II/0057/G 28.10.2021. The Icelandic and Norwegian CHMP
Novartis Europharm Limited, Rapporteur: Filip Members were in agreement with the CHMP
Josephson recommendation.
Opinion adopted on 28.10.2021.

Levetiracetam SUN - levetiracetam - Request for supplementary information adopted

EMEA/H/C/002051/II/0026 with a specific timetable.
Sun Pharmaceutical Industries Europe B.V.,
Generic, Generic of Keppra, Rapporteur:
Konstantinos Markopoulos
Request for Supplementary Information adopted
on 21.10.2021.

Lonquex - lipegfilgrastim - Positive Opinion adopted by consensus on

EMEA/H/C/002556/II/0066 28.10.2021. The Icelandic and Norwegian CHMP
Teva B.V., Rapporteur: Outi Mäki-Ikola Members were in agreement with the CHMP
Opinion adopted on 28.10.2021. recommendation.

Lydisilka - drospirenone / estetrol -

EMEA/H/C/005382/II/0003
Estetra SRL, Duplicate, Duplicate of Drovelis,
Rapporteur: Kristina Dunder
Request for Supplementary Information adopted
on 23.09.2021.

MabThera - rituximab - Positive Opinion adopted by consensus on

EMEA/H/C/000165/II/0186 28.10.2021. The Icelandic and Norwegian CHMP
Roche Registration GmbH, Rapporteur: Sinan B. Members were in agreement with the CHMP
Sarac recommendation.
Opinion adopted on 28.10.2021.
Request for Supplementary Information adopted
on 09.09.2021.

Menveo - Meningococcal group A, C, W135

and Y conjugate vaccine -
EMEA/H/C/001095/II/0103
GSK Vaccines S.r.l, Rapporteur: Johann
Lodewijk Hillege
Request for Supplementary Information adopted
on 02.09.2021.

Mosquirix - plasmodium falciparum and

hepatitis B vaccine (recombinant,
adjuvanted) -

EMA/CHMP/625004/2021 Page 12/67

EMEA/H/W/002300/II/0059/G
GlaxoSmithkline Biologicals SA, Rapporteur: Jan
Mueller-Berghaus

Nulojix - belatacept - See 9.1

EMEA/H/C/002098/II/0065/G
Bristol-Myers Squibb Pharma EEIG, Rapporteur:
Filip Josephson
Request for Supplementary Information adopted
on 14.10.2021, 25.03.2021, 12.11.2020,
12.03.2020.

Nulojix - belatacept - Positive Opinion adopted by consensus on

EMEA/H/C/002098/II/0076 28.10.2021. The Icelandic and Norwegian CHMP
Bristol-Myers Squibb Pharma EEIG, Rapporteur: Members were in agreement with the CHMP
Filip Josephson recommendation.
Opinion adopted on 28.10.2021.

Ontruzant - trastuzumab - Positive Opinion adopted by consensus on

EMEA/H/C/004323/II/0032 21.10.2021. The Icelandic and Norwegian CHMP
Samsung Bioepis NL B.V., Rapporteur: Karin Members were in agreement with the CHMP
Janssen van Doorn recommendation.
Opinion adopted on 21.10.2021.
Request for Supplementary Information adopted
on 17.06.2021.

OPDIVO - nivolumab - Positive Opinion adopted by consensus on

EMEA/H/C/003985/II/0106/G 28.10.2021. The Icelandic and Norwegian CHMP
Bristol-Myers Squibb Pharma EEIG, Rapporteur: Members were in agreement with the CHMP
Blanca Garcia-Ochoa recommendation.
Opinion adopted on 28.10.2021.
Request for Supplementary Information adopted
on 16.09.2021.

Rhokiinsa - netarsudil -
EMEA/H/C/004583/II/0007/G
Aerie Pharmaceuticals Ireland Limited,
Rapporteur: Jayne Crowe

Rixubis - nonacog gamma - Positive Opinion adopted by consensus on

EMEA/H/C/003771/II/0041/G 28.10.2021. The Icelandic and Norwegian CHMP
Baxalta Innovations GmbH, Rapporteur: Andrea Members were in agreement with the CHMP
Laslop recommendation.
Opinion adopted on 28.10.2021.

RoActemra - tocilizumab -
EMEA/H/C/000955/II/0103/G
Roche Registration GmbH, Rapporteur: Jan
Mueller-Berghaus

Skyrizi - risankizumab - Positive Opinion adopted by consensus on

EMEA/H/C/004759/II/0017/G 28.10.2021. The Icelandic and Norwegian CHMP
AbbVie Deutschland GmbH & Co. KG, Members were in agreement with the CHMP
Rapporteur: Peter Kiely recommendation.

EMA/CHMP/625004/2021 Page 13/67

Opinion adopted on 28.10.2021.
Request for Supplementary Information adopted
on 23.09.2021.

Vaxzevria - COVID 19 Vaccine (ChAdOx1 S

[recombinant]) -
EMEA/H/C/005675/II/0021/G
AstraZeneca AB, Rapporteur: Sol Ruiz
Request for Supplementary Information adopted
on 16.09.2021, 22.07.2021, 24.06.2021.

Vaxzevria - COVID 19 Vaccine (ChAdOx1 S Positive Opinion adopted by consensus on

[recombinant]) - 03.11.2021. The Icelandic and Norwegian CHMP
EMEA/H/C/005675/II/0035/G Members were in agreement with the CHMP
AstraZeneca AB, Rapporteur: Sol Ruiz recommendation.
Opinion adopted on 03.11.2021.
Request for Supplementary Information adopted
on 10.09.2021, 19.08.2021.

Verkazia - ciclosporin - Positive Opinion adopted by consensus on

EMEA/H/C/004411/II/0013/G, Orphan 28.10.2021. The Icelandic and Norwegian CHMP
Santen Oy, Duplicate, Duplicate of IKERVIS, Members were in agreement with the CHMP
Rapporteur: Peter Kiely recommendation.
Opinion adopted on 28.10.2021.
Request for Supplementary Information adopted
on 24.06.2021, 25.03.2021.

VITRAKVI - larotrectinib -
EMEA/H/C/004919/II/0017
Bayer AG, Rapporteur: Filip Josephson
Request for Supplementary Information adopted
on 30.09.2021.

Zavicefta - ceftazidime / avibactam - Request for supplementary information adopted

EMEA/H/C/004027/II/0027/G with a specific timetable.
Pfizer Ireland Pharmaceuticals, Rapporteur:
Ingrid Wang
Request for Supplementary Information adopted
on 28.10.2021, 09.09.2021.

Zercepac - trastuzumab -
EMEA/H/C/005209/II/0013/G
Accord Healthcare S.L.U., Rapporteur: Sol Ruiz

WS2135/G Positive Opinion adopted by consensus on

Rixathon-EMEA/H/C/003903/WS2135/ 28.10.2021. The Icelandic and Norwegian CHMP
0052/G Members were in agreement with the CHMP
Riximyo-EMEA/H/C/004729/WS2135/ recommendation.
0053/G
Sandoz GmbH, Lead Rapporteur: Jan Mueller-
Berghaus
Opinion adopted on 28.10.2021.

WS2164/G

EMA/CHMP/625004/2021 Page 14/67

Blitzima-EMEA/H/C/004723/WS2164/
0047/G
Truxima-EMEA/H/C/004112/WS2164/
0051/G
Celltrion Healthcare Hungary Kft., Duplicate,
Duplicate of Truxima, Lead Rapporteur: Sol Ruiz

B.5.2. CHMP assessed procedures scope: Non-Clinical and Clinical aspects

Adempas - riociguat -
EMEA/H/C/002737/II/0033/G, Orphan
Bayer AG, Rapporteur: Johann Lodewijk Hillege,
“Group of variations:
Type II C.I.4. update to SmPC section 4.8 and
5.1 based on the submission of the final clinical
study reports of the Phase III long-term
extension study PATENT-2.
Type II C.I.4. update to SmPC section 4.8 and
5.1 based on the submission of the final clinical
study reports of the Phase III long-term
extension study CHEST-2.”

Calquence - acalabrutinib -
EMEA/H/C/005299/II/0004
AstraZeneca AB, Rapporteur: Filip Josephson,
“Submission of the final report of the nonclinical
study 20266648 (5336BV) (Acalabrutinib:
Neutral Red Uptake Phototoxicity Assay in
BALB/c 3T3 Mouse Fibroblasts), in response to
the CHMP recommendation to submit results
from a modified 3T3 NRU phototoxicity study
with adjusted wavelengths. This variation does
not propose amendments to the PI.”
Request for Supplementary Information adopted
on 16.09.2021, 20.05.2021.

CellCept - mycophenolate mofetil -

EMEA/H/C/000082/II/0165/G
Roche Registration GmbH, Rapporteur: Sinan B.
Sarac, “C.I.4 (Type II) - Update of section 5.1
of the SmPC with recent findings from a clinical
Pharmacology position paper on Mycophenolate
mechanism of Action.
- C.I.4 (Type II) - Update of section 5.2 of the
SmPC to add new information to the distribution
and elimination subsections based on a Clinical
Pharmacology Position Paper.
- C.I.4 (Type II) - Update of section 5.2 of the
SmPC to amend the existing information on
patients taking oral contraceptives based on

EMA/CHMP/625004/2021 Page 15/67

study Roche Report N-181041/ BP 15543.
Section 4.5 of the SmPC has been updated
accordingly.
- C.I.Z (Type IB) - Update of section 2 and
section 6 of the Package Leaflet to implement
recommendations from NCA (Ireland) and EMA.
The Package Leaflet is updated accordingly. In
addition, the Marketing Authorisation Holder
(MAH) has taken the opportunity to implement
minor editorial changes to the SmPC and
Package Leaflet. Furthermore, the PI is being
brought in line with the latest QRD template
version 10.2.”
Request for Supplementary Information adopted
on 16.09.2021.

Cimzia - certolizumab pegol -

EMEA/H/C/001037/II/0101
UCB Pharma S.A., Rapporteur: Kristina Dunder,
“C.I.4: Update of section 4.6 of the SmPC in
order to update information on pregnancy based
on non-interventional data from the UCB Global
Safety Database on prospective Cimzia-exposed
pregnancies with known outcomes; the Package
Leaflet is updated accordingly.”

Copiktra - duvelisib -
EMEA/H/C/005381/II/0002
Secura Bio Limited, Rapporteur: Sinan B. Sarac,
“Update of section 5.1 of the SmPC based on
the final overall survival results from study IPI-
145-07, an interventional Phase 3 study of
duvelisib (IPI-145) vs ofatumumab in patients
with relapsed or refractory Chronic Lymphocytic
leukaemia/Small Lymphocytic Lymphoma.”

Cresemba - isavuconazole - Positive Opinion adopted by consensus on

EMEA/H/C/002734/II/0036, Orphan 28.10.2021. The Icelandic and Norwegian CHMP
Basilea Pharmaceutica Deutschland GmbH, Members were in agreement with the CHMP
Rapporteur: Johann Lodewijk Hillege, “Update of recommendation.
section 5.1 of the SmPC in order to harmonise
the EUCAST breakpoints to those published in
the EUCAST breakpoint tables version 10.0,
valid from 4 February 2020 for interpretation of
minimum inhibitory concentrations (MICs) of
antifungal agents. In addition, the MAH took the
opportunity to update the list of local
representatives in the Package Leaflet.”
Opinion adopted on 28.10.2021.

Dapivirine Vaginal Ring 25 mg - dapivirine Request for supplementary information adopted

- EMEA/H/W/002168/II/0012/G with a specific timetable.

EMA/CHMP/625004/2021 Page 16/67

International Partnership for Microbicides
Belgium AISBL, Rapporteur: Paula Boudewina
van Hennik, “Update of sections 4.5 and 5.2 of
the SmPC in order to add drug-drug interaction
information with vaginal products (e.g. vaginal
miconazole) that are metabolised by CYP and
UGT enzymes and to update pharmacokinetic
information based on the final study reports of 3
in vitro enzyme/transporter studies evaluating
the interactions between dapivirine and
transporters (study NPK/0025), dapivirine-
miconazole interactions on CYP (study
NPK/0026) and UGT enzymes (study
NPK/0027).
Submission of the final report from study
evaluating the impact of dapivirine and
miconazole on cellular tight junctions and
assessing the impact of miconazole on
dapivirine tissue permeability (study
NPK/0028).
These 4 in vitro studies were submitted to fulfil
post-authorisation measures (REC) requested in
the initial marketing authorisation application
assessment report.”
Request for Supplementary Information adopted
on 28.10.2021.

Dengvaxia - dengue tetravalent vaccine

(live, attenuated) -
EMEA/H/C/004171/II/0013
Sanofi Pasteur, Rapporteur: Christophe Focke,
“Update of sections 4.2 and 5.1 of the SmPC
based on final results from study CYD65, listed
as a category 3 study in the RMP; this is a
Phase II, observer-blind, placebo-controlled trial
in order to assess Immunogenicity and Safety of
Tetravalent Dengue Vaccine Given in 1-, 2-, or
3-Dose Schedules Followed by a Single
Booster.”
Request for Supplementary Information adopted
on 20.05.2021, 10.12.2020.

Empliciti - elotuzumab - Positive Opinion adopted by consensus on

EMEA/H/C/003967/II/0028 21.10.2021. The Icelandic and Norwegian CHMP
Bristol-Myers Squibb Pharma EEIG, Rapporteur: Members were in agreement with the CHMP
Paula Boudewina van Hennik, “C.I.4: Update of recommendation.
section 5.1 of the SmPC in order to update
efficacy data from the final CSR for study
CA204125. This is an open label, randomized
phase 2 Trial of Pomalidomide/Dexamethasone
With or Without Elotuzumab in RRMM. In

EMA/CHMP/625004/2021 Page 17/67

addition, the MAH took the opportunity to
remove the list of local representatives in the
Package Leaflet and update the address of the
manufacturer.”
Opinion adopted on 21.10.2021.

Epidyolex - cannabidiol -
EMEA/H/C/004675/II/0015, Orphan
GW Pharma (International) B.V., Rapporteur:
Sinan B. Sarac, “Update of sections 4.5 and 5.1
of the SmPC to add drug-drug interaction
information with everolimus and P-gp substrates
following the assessment the study
GWCP19195, a phase I open-label
pharmacokinetic drug-drug interaction trial to
investigate the effect of cannabidiol on the
pharmacokinetics of everolimus in healthy
subject. In addition, the MAH took the
opportunity to introduce editorial updates in
section 5.1 and section 4.9.”

Epidyolex - cannabidiol -
EMEA/H/C/004675/II/0016, Orphan
GW Pharma (International) B.V., Rapporteur:
Sinan B. Sarac, “Update of section 5.3 of the
SmPC to reflect on the conclusions of study
GWTX1504, 104 week oral (gavage)
administration carcinogenicity study in mouse.”

Evrysdi - risdiplam - Positive Opinion adopted by consensus on

EMEA/H/C/005145/II/0002, Orphan 28.10.2021. The Icelandic and Norwegian CHMP
Roche Registration GmbH, Rapporteur: Bruno Members were in agreement with the CHMP
Sepodes, “Update of sections 4.8 and 5.1 of the recommendation.
SmPC based on long-term results from study
FIREFISH (BP39056) listed as a category 3
study in the RMP; this is an observational OLE
safety and efficacy study. In addition, the MAH
took the opportunity to introduce editorial
changes to SmPC and to the Instruction for use
(IFU).”
Opinion adopted on 28.10.2021.

Feraccru - ferric maltol - Request for supplementary information adopted

EMEA/H/C/002733/II/0033 with a specific timetable.
Norgine B.V., Rapporteur: Maria Concepcion
Prieto Yerro, “to remove haemoglobin threshold
from section 4.4 ‘Special warnings and
precautions for use’ of summary of product
characteristics for Feraccru Capsules 30 mg,
deleting the reference made that states
"Feraccru is not recommended for use in
patients with haemoglobin (Hb) <9.5 g/dl."

EMA/CHMP/625004/2021 Page 18/67

Request for Supplementary Information adopted
on 21.10.2021, 22.07.2021.

Fetcroja - cefiderocol -
EMEA/H/C/004829/II/0006/G
Shionogi B.V., Rapporteur: Filip Josephson,
“Submission of the final report from the in vitro
RIS correlation study S-649266-PF-415-N (REC
003), to address CYP3A4 induction by
cefiderocol.
In addition, the MAH submitted the final report
of in vitro study S-649266-CPK-008-C to
investigate the DDI between cefiderocol as a
CYP3A4 inducer and Midazolam using
physiologically-based pharmacokinetic model.”

Giotrif - afatinib -
EMEA/H/C/002280/II/0039/G
Boehringer Ingelheim International GmbH,
Rapporteur: Filip Josephson, “Update of sections
4.2, 5.1 and 5.2 of the SmPC in order to update
the description of paediatric information based
on results of paediatric study 1200.120. This is
in compliance with a completed paediatric
investigation plan which does not support a
paediatric indication. The Package Leaflet is
updated accordingly. The ATC code is also
updated. In addition, the MAH took the
opportunity to make some minor administrative
changes to the labelling and package leaflet.”
Request for Supplementary Information adopted
on 16.09.2021.

Imfinzi - durvalumab - Request for supplementary information adopted

EMEA/H/C/004771/II/0034 with a specific timetable.
AstraZeneca AB, Rapporteur: Sinan B. Sarac,
“Update of sections 4.4 and 4.8 of the SmPC in
order to reflect the outcome of the re-defined
process to identify and calculate immune-
mediated Adverse Event (imAE) rates from
clinical study and pooled datasets within the
durvalumab development programmes. In
addition, the MAH implemented minor editorial
corrections to sections 4.4 and 5.1 of the
SmPC.”
Request for Supplementary Information adopted
on 21.10.2021.

Kanuma - sebelipase alfa -

EMEA/H/C/004004/II/0032, Orphan
Alexion Europe SAS, Rapporteur: Karin Janssen
van Doorn, “Update of section 4.2 of the SmPC

EMA/CHMP/625004/2021 Page 19/67

in order to introduce a new posology regimen
(higher starting dose of 3mg/kg once weekly)
based on cumulative data from clinical studies
and real-world clinical practice for patients with
Rapidly Progressive LAL deficiency presenting
within the first six months of life. Consequently,
the dosing information for patients with Rapidly
Progressive LAL deficiency and paediatric and
adult patients with LAL deficiency is modified. In
addition, editorial update is made in sections
4.8, 5.1, 5.2 and 6.6 following the new posology
regimen. The Package Leaflet is updated
accordingly.”
Request for Supplementary Information adopted
on 16.09.2021.

Kyprolis - carfilzomib -
EMEA/H/C/003790/II/0051/G, Orphan
Amgen Europe B.V., Rapporteur: Blanca Garcia-
Ochoa, “A.6 The ATC code of the product is
updated
C.I.4, Update of section 4.2 of the SmPC in
order to modify administration instructions of
daratumumab when Kyprolis is dosed in
combination with daratumumab and
dexamethasone, based on results from efficacy
and safety studies MMY2040 (ongoing phase 2),
MMY1001 (completed phase 1b) and CANDOR
(ongoing phase 3).”
Request for Supplementary Information adopted
on 22.07.2021.

Lynparza - olaparib -
EMEA/H/C/003726/II/0048
AstraZeneca AB, Rapporteur: Alexandre Moreau,
PRAC Rapporteur: Amelia Cupelli, “Update of
section 5.1 of the olaparib tablet SmPC based
on results from study D0816C00020 (OPINION)
listed as a PAES in the Annex II; this is a Phase
IIIb single arm, multicentre study, investigating
olaparib as a maintenance treatment in patients
with platinum-sensitive relapsed ovarian,
fallopian tube or primary peritoneal cancer
following 2 or more lines of platinum based
chemotherapy and who did not have a known
deleterious or suspected deleterious gBRCA
mutation; the Annex II is updated accordingly.
The RMP version 22.1 has also been submitted.”
Request for Supplementary Information adopted
on 02.09.2021.

EMA/CHMP/625004/2021 Page 20/67

Mayzent - siponimod -
EMEA/H/C/004712/II/0011/G
Novartis Europharm Limited, Rapporteur: Sinan
B. Sarac, “- Update of sections 4.4 and 4.5 of
the SmPC to add information in case of
administration of non-live attenuated vaccines,
based on the vaccination study A2130.
- Update of section 4.5 of the SmPC to clarify
the CYP2C9/CYP3A4 inhibitors/inducers
information.
- Update of section 5.2 to add information
regarding CYP2C9 genotypes less frequent
alleles.”
Request for Supplementary Information adopted
on 23.09.2021.

NexoBrid - concentrate of proteolytic

enzymes enriched in bromelain -
EMEA/H/C/002246/II/0049, Orphan
MediWound Germany GmbH, Rapporteur: Janet
Koenig, “Update of sections 4.2, 4.4, 4.8, 4.9,
5.1 and 5.2 of the SmPC based on interim
results from study MW2010-03-02 (DETECT)
listed as an obligation in the Annex II; this is a
multicenter, multinational, randomized,
controlled, assessor blinded, three-arm study
performed in subjects with thermal burns, to
evaluate the efficacy and safety of NexoBrid
compared to Gel Vehicle and compared to
Standard of Care. The submitted Clinical Study
Report includes data of Acute Phase and 12M
Follow Up Period. The MAH also took the
opportunity to submit integrated pooled
analyses of efficacy and safety data obtained
from phase 2 and phase 3 clinical studies to
provide a comprehensive assessment of the
safety and efficacy of NexoBrid. The Package
Leaflet is updated accordingly.”
Request for Supplementary Information adopted
on 25.03.2021, 15.10.2020.

Nuceiva - botulinum toxin type A -

EMEA/H/C/004587/II/0017
Evolus Pharma Limited, Rapporteur: Peter Kiely,
“Submission of the final reports of the non-
interventional immunogenicity analysis (RMP cat
3 study).”
Request for Supplementary Information adopted
on 23.09.2021.

OCALIVA - obeticholic acid -

EMEA/H/C/004093/II/0029, Orphan

EMA/CHMP/625004/2021 Page 21/67

Intercept Pharma International Limited,
Rapporteur: Blanca Garcia-Ochoa, “Update of
sections 4.2, 4.5 and 5.2 of the SmPC in order
to clarify information on posology
recommendations in renally impaired patients
and add information on pharmacokinetic
properties following the results from study 474-
120 (a Phase I, Open-Label Study to Investigate
the Effect of Renal Impairment on the Single-
Dose Pharmacokinetics of Obeticholic Acid).
Editorial changes have also been made to
section 4.5.”
Request for Supplementary Information adopted
on 16.09.2021.

Opsumit - macitentan -
EMEA/H/C/002697/II/0043, Orphan
Janssen-Cilag International N.V., Rapporteur:
Maria Concepcion Prieto Yerro, “C.I.4 :Update of
sections 4.2 and 4.4 of the SmPC to remove a
sentence and a warning on the limited clinical
experience in patients over the age of 75 years,
following the recommendation of the
EMEA/H/C/PSUSA/00010115/202010 procedure
to remove ‘Elderly patients’ as missing
information in the RMP. The Package Leaflet is
being updated accordingly. In addition, the MAH
took this opportunity to update the Package
Leaflet to include a section on Male fertility and
align it with the currently approved information
in SmPC, sections 4.6 Fertility, pregnancy, and
lactation and 5.3 Preclinical safety.”

Opsumit - macitentan -
EMEA/H/C/002697/II/0044, Orphan
Janssen-Cilag International N.V., Rapporteur:
Maria Concepcion Prieto Yerro, “C.I.4: Update of
SmPC sections 4.8 and 5.1, based on the long-
term follow-up data from SERAPHIN open-label
(OL) study. SERAPHIN OL study was a long-
term single-arm open-label extension study of
the SERAPHIN double-blind (DB) study, to
assess the safety and tolerability of macitentan
in patients with symptomatic pulmonary arterial
hypertension (PAH) that have completed the DB
study or that experienced a morbidity event and
for who a written approval to roll over into the
OL study was obtained by the sponsor.”

Phesgo - pertuzumab / trastuzumab - Request for supplementary information adopted

EMEA/H/C/005386/II/0004 with a specific timetable.
Roche Registration GmbH, Rapporteur: Sinan B.

EMA/CHMP/625004/2021 Page 22/67

Sarac, “Update in section 4.8, Undesirable
Effects, to present the pooled data from Perjeta
and Phesgo studies.
In addition to this, the MAH has taken the
opportunity to introduce minor updates in the
SmPC and the package leaflet:
• Update in section 9 of the SmPC to reflect the
date of first authorisation
• Editorial update in section 4 of the package
leaflet to add a space
• Update in section 6 of the package leaflet to
adapt to the revised QRD Template v10.2”
Request for Supplementary Information adopted
on 21.10.2021, 22.07.2021.

Plenadren - hydrocortisone - Request for supplementary information adopted

EMEA/H/C/002185/II/0034, Orphan with a specific timetable.
Shire Services BVBA, Rapporteur: Kristina
Dunder, “Update of section 4.8 of the SmPC to
add bradycardias a new ADR with frequency
unknown.”
Request for Supplementary Information adopted
on 28.10.2021.

Pradaxa - dabigatran etexilate -

EMEA/H/C/000829/II/0128
Boehringer Ingelheim International GmbH,
Rapporteur: Sinan B. Sarac, “C.I.4,
Update of section 4.2 of the SmPC in order to
update the dosing information for Pradaxa
coated granules and to introduce a new format
of the dosing tables for all dosage forms of
Pradaxa to avoid incorrect interpretation and
possible mistakes.
In addition, a guidance related to the Schwartz
formula is proposed to be included in section
4.2 of the SmPC. The Package Leaflet was
updated accordingly. Furthermore, the MAH
took the opportunity to request introduction of
the link to a training video by scanning the QR
code in Annex IIIA and IIIB and to include
additional updates to Annex IIIA and mock-
ups.”
Request for Supplementary Information adopted
on 22.07.2021.

REKAMBYS - rilpivirine - Request for supplementary information adopted

EMEA/H/C/005060/II/0006 with a specific timetable.
Janssen-Cilag International N.V., Rapporteur:
Johann Lodewijk Hillege, “Update of section 4.4
of the SmPC in order to amend an existing
warning on section post-injections reactions,

EMA/CHMP/625004/2021 Page 23/67

based on the availability of new information
from ongoing phase 3/3b clinical trials. Section
2 of the Package Leaflet is updated accordingly.
In addition, the MAH took the opportunity to
implement some minor editorial changes.”
Request for Supplementary Information adopted
on 21.10.2021.

Revestive - teduglutide -
EMEA/H/C/002345/II/0053, Orphan
Shire Pharmaceuticals Ireland Limited,
Rapporteur: Sinan B. Sarac, “Update of sections
4.2, 4.8, 5.1 and 5.2 of the SmPC in order to
update the Product information with results
from two studies included in the paediatric
investigation plan (PIP). Study SHP633-1 was
performed to evaluate the safety,
efficacy/pharmacodynamics (PD), and
pharmacokinetics (PK) of teduglutide in infants
4 to 12 months gestational age with SBS and
who are dependent on parenteral support. The
second study is a paediatric population PK
model including data from study SHP633-301.
The Package Leaflet was updated accordingly.
In addition, the MAH took the opportunity to
make editorial changes to section 4.5 of the
SmPC.”
Request for Supplementary Information adopted
on 14.10.2021, 24.06.2021.

Spikevax - COVID-19 mRNA vaccine Positive Opinion adopted by consensus on

(nucleoside-modified) - 25.10.2021. The Icelandic and Norwegian CHMP
EMEA/H/C/005791/II/0034 Members were in agreement with the CHMP
Moderna Biotech Spain, S.L., Rapporteur: Jan recommendation.
Mueller-Berghaus, “To update sections 2, 4.2,
4.4, 4.8, 5.1, 6.5 and 6.6 of the SmPC to
include a booster dose for Spikevax, based on
new clinical data from studies mRNA-1273-
P201, a Phase 2a, Randomized, Observer-Blind,
Placebo-Controlled, Dose-Confirmation Study to
Evaluate the Safety, Reactogenicity, and
Immunogenicity of mRNA-1273 SARS-CoV-2
Vaccine in Adults Aged 18 Years and Older
(NCT04405076), mRNA-1273-P301, an ongoing
Phase 3, Randomized, Stratified, Observer-
Blind, Placebo-Controlled Study to Evaluate the
Efficacy, Safety, and Immunogenicity of mRNA-
1273 SARS-CoV-2 Vaccine in Adults Aged 18
Years and Older (NCT04470427) and DMID 21-
0012, a Phase 1/2 Study of Delayed
Heterologous SARS-CoV-2 Vaccine Dosing

EMA/CHMP/625004/2021 Page 24/67

(Boost) After Receipt of EUA Vaccines
(NCT04889209). The labelling and the package
leaflet are updated accordingly.”
Opinion adopted on 25.10.2021.

Spinraza - nusinersen -
EMEA/H/C/004312/II/0023, Orphan
Biogen Netherlands B.V., Rapporteur: Bruno
Sepodes, “Update of section 5.1 of the SmPC to
include information on real-world use of
nusinersen in adults.”
Request for Supplementary Information adopted
on 16.09.2021.

TAGRISSO - osimertinib -
EMEA/H/C/004124/II/0045
AstraZeneca AB, Rapporteur: Blanca Garcia-
Ochoa, “Update of section 5.3 of the SmPC in
order to reflect the outcome of the 104 Week
Oral (Gavage) Carcinogenicity Study (507363)
in the Rat submitted as recommended by the
CHMP.”

Talzenna - talazoparib -
EMEA/H/C/004674/II/0010/G
Pfizer Europe MA EEIG, Rapporteur: Filip
Josephson, “Update of section 4.4 of the SmPC
in order to update the frequency of
myelodysplastic syndrome/acute myeloid
syndrome (MDS/AML) based on a cumulative
safety review; Update of section 5.1 of the
SmPC with the revised ATC code. In addition,
the MAH took the opportunity to update the list
of local representatives in the Package Leaflet
and make minor corrections in the SmPC and
PL.”
Request for Supplementary Information adopted
on 30.09.2021.

Vaxelis - diphtheria, tetanus, pertussis

(acellular, component), hepatitis b (rdna),
poliomyelitis (inact.) and haemophilus type
b conjugate vaccine (adsorbed) -
EMEA/H/C/003982/II/0088
MCM Vaccine B.V., Rapporteur: Christophe
Focke, “Update of section 5.1 of the SmPC in
order to include information about long-term
durability of the immune protection against HBV
infection based on study V419-013 A Hepatitis B
Vaccine Challenge Study to Demonstrate the
Durability of Protection Against Hepatitis B Virus
Infection in Healthy Children Vaccinated

EMA/CHMP/625004/2021 Page 25/67

Approximately 9 Years Previously With a 2- or
3-Dose Infant Series and Toddler Dose of
Vaxelis (study report P013V419). In addition,
the MAH is updating sections 4.7 and 4.8 of the
SmPC to implement EMA proposed wording and
a typo error.
The MAH took the opportunity to update the list
of local representatives in the PL and implement
minor editorial changes in sections 4.8 and 6.6
of the SmPC and section 2 of the PL.
Furthermore, the PI is brought in line with the
latest QRD template version 10.2 rev. 1.”

Vectibix - panitumumab - Positive Opinion adopted by consensus on

EMEA/H/C/000741/II/0097 21.10.2021. The Icelandic and Norwegian CHMP
Amgen Europe B.V., Rapporteur: Ingrid Wang, Members were in agreement with the CHMP
“Update of sections 4.4 and 4.8 of the SmPC in recommendation.
order to add the risk of corneal perforation to
the risks of keratitis and ulcerative keratitis and
to add corneal perforation (including
keratorhexis, which also includes lowest level
term corneal rupture) to the list of the adverse
reactions, respectively following a safety
evaluation.
The package leaflet has been updated
accordingly. In addition, the applicant took the
opportunity to remove frequency information
due to variations in case frequency in section
4.8 of the SmPC and section 4 of the PL.
Furthermore, the PI is being brought in line with
the latest QRD template (version 10.2) and
minor editorial changes were made in the PL.”
Opinion adopted on 21.10.2021.
Request for Supplementary Information adopted
on 22.07.2021.

Veltassa - patiromer -
EMEA/H/C/004180/II/0024
Vifor Fresenius Medical Care Renal Pharma
France, Rapporteur: Jayne Crowe, “Update of
section 4.2 of the SmPC in order to update the
posology with information to add the option to
use various liquids and soft foods instead of the
currently approved options (water, apple,
cranberry juice) for preparation of Veltassa oral
suspension. This is based on results from a new
compatibility study report of Veltassa with
juices/liquids and soft foods (REP074062TC).
The Package Leaflet is updated accordingly.”
Request for Supplementary Information adopted
on 16.09.2021.

EMA/CHMP/625004/2021 Page 26/67

Viread - tenofovir disoproxil -
EMEA/H/C/000419/II/0204
Gilead Sciences Ireland UC, Rapporteur: Jean-
Michel Race, Co-Rapporteur: Maria Concepcion
Prieto Yerro, PRAC Rapporteur: Nathalie Gault,
“Submission of final study report for study GS-
US-174-0144, listed as category 3 study in the
RMP for Viread. This is a randomized, double-
blind evaluation of the antiviral efficacy, safety
and tolerability of Tenofovir disporoxil fumarate.
This application fulfils the Article 46
commitment to provide the final week 192 study
results for clinical measure 'Study 5'
(study GS_US_174-0144) listed in the PIP.
Section 5.1 of the SmPC is being amended
accordingly. Additionally, the risk minimisation
measures for paediatrics are being removed
from the RMP and Annex II of the PI. The
Package Leaflet has been updated accordingly.
The MAH took the opportunity to implement
minor linguistic amendments throughout the PI.
In addition, the expression of lactose content in
Annex I for the tablets was changed, to refer to
lactose base (not as monohydrate), in line with
current practice. The RMP version 25.1 has been
submitted.”
Request for Supplementary Information adopted
on 08.07.2021.

Xolair - omalizumab - Positive Opinion adopted by consensus on

EMEA/H/C/000606/II/0109 21.10.2021. The Icelandic and Norwegian CHMP
Novartis Europharm Limited, Rapporteur: Members were in agreement with the CHMP
Kristina Dunder, “Update of section 5.1 of the recommendation.
SmPC in order to update information on efficacy
and safety based on final results from study
WA40169; this is a single-arm, open-label
extension study to evaluate the safety, efficacy
and durability of response of Xolair in an open-
label setting in adult patients with chronic
rhinosinusitis with nasal polyps (CRSwNP).”
Opinion adopted on 21.10.2021.

Zejula - niraparib - Positive Opinion adopted by consensus on

EMEA/H/C/004249/II/0032/G, Orphan 28.10.2021. The Icelandic and Norwegian CHMP
GlaxoSmithKline (Ireland) Limited, Rapporteur: Members were in agreement with the CHMP
Ingrid Wang, “Submission of the final reports recommendation.
from two non-clinical studies (TSRO/REP/07-08-
09 and KB-0139-DV-HB) investigating the
carboxylesterase (CE) and UDP-
glucuronosyltransferase (UGT) enzymes
involved in the metabolism of niraparib.”

EMA/CHMP/625004/2021 Page 27/67

Opinion adopted on 28.10.2021.

WS2114
Mekinist-EMEA/H/C/002643/WS2114/
0050
Tafinlar-EMEA/H/C/002604/WS2114/
0054
Novartis Europharm Limited, Lead Rapporteur:
Filip Josephson, “Update of section 5.1 of the
SmPC with the final efficacy data from study
BRF113928 (CDRB436E2201), conducted in
patients with stage IV BRAF V600 mutant
NSCLC, in fulfilment of a post-authorisation
measure (REC) from the initial MA.”

WS2130/G
Elebrato Ellipta-EMEA/H/C/004781/
WS2130/0023/G
Temybric Ellipta-EMEA/H/C/005254/
WS2130/0011/G
Trelegy Ellipta-EMEA/H/C/004363/
WS2130/0020/G
GlaxoSmithKline Trading Services Limited, Lead
Rapporteur: Peter Kiely, “Update of section 4.8
of the SmPC to add the ADR (dysgeusia’) and
change frequencies for already reported ADRs
(‘nasopharyngitis’, ‘viral respiratory tract
infection’, and ‘dysphonia’) based on an updated
safety analysis. The PL is updated accordingly.”
Request for Supplementary Information adopted
on 16.09.2021.

WS2156 Request for supplementary information adopted

Nuwiq-EMEA/H/C/002813/WS2156/0047 with a specific timetable.
Vihuma-EMEA/H/C/004459/WS2156/
0029
Octapharma AB, Lead Rapporteur: Jan Mueller-
Berghaus, “Submission of the final report from
study GENA-99 including the integrated analysis
report of studies GENA-99, GENA-13, GENA-15,
GENA-21, GENA-21b and GENA-100. GENA-99
is a Prospective, multinational, non-
interventional post-authorisation study to
document the long-term immunogenicity,
safety, and efficacy of Human-cl rhFVIII
(simoctocog alfa) in patients with haemophilia A
treated in routine clinical practice.”
Request for Supplementary Information adopted
on 28.10.2021.

EMA/CHMP/625004/2021 Page 28/67

B.5.3. CHMP-PRAC assessed procedures

ADCETRIS - brentuximab vedotin -

EMEA/H/C/002455/II/0093, Orphan
Takeda Pharma A/S, Rapporteur: Paula
Boudewina van Hennik, PRAC Rapporteur:
Menno van der Elst, “Update of sections 4.2,
4.8, 5.1, 5.2, and 6.6 of the SmPC based on
results from study C25004, an open-label study
in order to assess the safety and tolerability, of
brentuximab vedotin when combined with
multiagent chemotherapy regimen for first-line
treatment of advanced-stage Hodgkin
lymphoma in paediatric patients. The RMP
version 16 has also been submitted.”
Request for Supplementary Information adopted
on 30.09.2021.

Adenuric - febuxostat -
EMEA/H/C/000777/II/0062
Menarini International Operations Luxembourg
S.A., Rapporteur: Andrea Laslop, PRAC
Rapporteur: Jan Neuhauser, “C.I.4 - Update of
sections 4.4 and 4.5 of the SmPC in order to
amend an existing warning on the drug-drug
interaction information with
mercaptopurine/azathioprine based on final
results from study FAI-01 listed as a category 3
study in the RMP; this is a phase I, drug-drug
interaction study investigating the PK profile of
6-mercaptopurine following co-administration of
two doses febuxostat and azathioprine in
healthy subjects. The RMP version 9.0 has also
been submitted.”
Request for Supplementary Information adopted
on 16.09.2021.

Defitelio - defibrotide - Request for supplementary information adopted

EMEA/H/C/002393/II/0056, Orphan with a specific timetable.
Gentium S.r.l., Rapporteur: Kristina Dunder,
PRAC Rapporteur: Ulla Wändel Liminga,
“Submission of the final report from study 15-
007 listed as a specific obligation in the Annex II
of the Product Information. This is a phase 3,
randomised, adaptive study (15-007) of
Defibrotide vs. best supportive care in the
prevention of hepatic venoocclusive disease in
adult and paediatric patients undergoing
hematopoietic stem cell transplant (HSCT). The
RMP version 9 has also been submitted.
The MAH has also taken the opportunity to align
the PI to the latest QRD template 10.2 which

EMA/CHMP/625004/2021 Page 29/67

replaces the United Kingdom with United
Kingdom (Northern Ireland) in the PIL.
In addition, the MAH is correcting the following
errata during the linguistic review of the PI:
correction of the paragraph number for
Regulation (EC) No 726.2004 which was cited
incorrectly in Annex II of the French PI and
formatting updates to Norwegian and Swedish
language PIs.”
Request for Supplementary Information adopted
on 28.10.2021, 08.07.2021.

GIVLAARI - givosiran - Request for supplementary information adopted

EMEA/H/C/004775/II/0006, Orphan with a specific timetable.
Alnylam Netherlands B.V., Rapporteur: Paula
Boudewina van Hennik, PRAC Rapporteur:
Martin Huber, “Type II C.I.4 : Update of SmPC
section 4.8 to add 'blood homocysteine increase'
as a new ADR and update to SmPC section 4,4
to add a related warning. The package leaflet is
being updated accordingly. RMPv1.1 is also
being submitted: consequences of blood
homocysteine increase is being added as a new
important potential risk, the clinical and post-
marketing exposure is being updated and the
due dates for ALN-AS1-002 and ALN-AS1-003
final study reports are being postponed.
In addition, the MAH took the opportunity to
make editorial changes to the Product
Information in other EU languages and to
update the contact number of the local
representatives for Malta and Cyprus.”
Request for Supplementary Information adopted
on 28.10.2021, 02.09.2021.

Increlex - mecasermin -
EMEA/H/C/000704/II/0067
Ipsen Pharma, Rapporteur: Outi Mäki-Ikola,
PRAC Rapporteur: Kirsti Villikka, “Update of the
conditions of the non-interventional PASS which
is listed as a specific obligation in Annex II, by
using different criteria of patient exposure and
long-term follow up to assess the relevant
safety data, with consequential amendment of
the study completion date. The RMP version 13
has also been submitted, also including an
amended Global registry protocol (amendment
8). The Package Leaflet is updated accordingly.
In addition, the MAH took the opportunity to
update the list of local representatives in the
Package Leaflet, in line with the latest QRD

EMA/CHMP/625004/2021 Page 30/67

template version 10.2 rev.1.”
Request for Supplementary Information adopted
on 22.07.2021.

Natpar - parathyroid hormone -

EMEA/H/C/003861/II/0029, Orphan
Takeda Pharmaceuticals International AG,
Rapporteur: Karin Janssen van Doorn, PRAC
Rapporteur: Rhea Fitzgerald, “Submission of the
final results of study SHP634-101: An Open-
Label, Randomized, Crossover Study to Assess
the Pharmacokinetic and Pharmacodynamic
Profiles of Once-Daily and Twice-Daily Dose
Regimens of recombinant human Parathyroid
Hormone (rhPTH[1-84]) Administered
Subcutaneously to Subjects with
Hypoparathyroidism. Further clinical evaluation
of an alternative dosing regimen is no longer
warranted, as outlined in the current specific
obligation (study SHP634-403). The conditional
marketing authorisation can therefore be
converted into a standard marketing
authorisation (no longer subject to a specific
obligation) valid for 5 years.”
Request for Supplementary Information adopted
on 24.06.2021.

NINLARO - ixazomib - Request for supplementary information adopted

EMEA/H/C/003844/II/0033, Orphan with a specific timetable.
Takeda Pharma A/S, Rapporteur: Armando
Genazzani, PRAC Rapporteur: Annika Folin,
“C.I.11 Submission of the final report for the
final analysis of OS for study C16010 listed as
an obligation in the Annex II of the Product
Information. This is a phase 3, randomized,
double-blind study to evaluate ixazomib in
combination with LenDex in adult patients with
relapsed and/or refractory multiple myeloma.
The Annex II and the RMP (submitted version
7.0) are updated accordingly.”
Request for Supplementary Information adopted
on 28.10.2021, 02.09.2021.

Piqray - alpelisib - Request for supplementary information adopted

EMEA/H/C/004804/II/0008/G with a specific timetable.
Novartis Europharm Limited, Rapporteur: Blanca
Garcia-Ochoa, PRAC Rapporteur: Menno van der See 9.1
Elst, “Update of section 5.1 of the SmPC based
on final results from study CBYL719C2301
(SOLAR-1) listed as a PAES in the Annex II; this
is a phase III, randomized, double-blind,
placebo controlled study of alpelisib in

EMA/CHMP/625004/2021 Page 31/67

combination with fulvestrant for men and
postmenopausal women with hormone receptor
positive, HER2-negative advanced breast cancer
which progressed on or after aromatase
inhibitor treatment; the Annex II is updated
accordingly. In addition, the MAH is updating
the ATC code in the SmPC. The RMP version 5.0
has also been submitted.”
Request for Supplementary Information adopted
on 28.10.2021.

Reagila - cariprazine - Request for supplementary information adopted

EMEA/H/C/002770/II/0023 with a specific timetable.
Gedeon Richter Plc., Rapporteur: Kristina
Dunder, PRAC Rapporteur: Ana Sofia Diniz
Martins, “Update of sections 4.4, 4.5, 4.6 and
5.2 of the SmPC in order to update
pharmacokinetic information based on final
results from RGH-188-302 (CAROLA) study
listed as a category 3 study in the RMP; this is
an open-label, single-arm, fixed-sequence,
phase 1 trial in female schizophrenia patients to
investigate the effect of multiple-dose
administration of cariprazine on the
pharmacokinetics of a combined oral
contraceptive containing ethinylestradiol and
levonorgestrel; the Package Leaflet is updated
accordingly. The RMP version 2.0 has also been
submitted. In addition, the MAH took the
opportunity to implement minor editorial
changes in sections 4.8 and 5.3 of the SmPC
and in the PL.”
Request for Supplementary Information adopted
on 28.10.2021.

Rubraca - rucaparib - See 9.1

EMEA/H/C/004272/II/0029
Clovis Oncology Ireland Limited, Rapporteur:
Blanca Garcia-Ochoa, PRAC Rapporteur: Annika
Folin, “Update of sections 4.4, 4.8 and 5.1 of
the SmPC based on final results from study CO-
338-043 (ARIEL4); this is a phase 3,
multicentre, open-label, randomised study
evaluating the efficacy and safety of rucaparib
versus chemotherapy for treatment of relapsed
ovarian cancer listed as a specific obligation in
the Annex II; the Package Leaflet is updated
accordingly. The RMP version 6.1 has also been
submitted. With this variation application, the
MAH requests for the Rubraca marketing
authorisation to no longer be subject to specific

EMA/CHMP/625004/2021 Page 32/67

obligations. The SmPC, Annex II and PL are
updated accordingly. In addition, the MAH took
the opportunity to make minor editorial changes
and bring the PI in line with the latest QRD
template version 10.2 Rev.1.”

Rydapt - midostaurin -
EMEA/H/C/004095/II/0018/G, Orphan
Novartis Europharm Limited, Rapporteur: Paula
Boudewina van Hennik, PRAC Rapporteur:
Marcia Sofia Sanches de Castro Lopes Silva,
“A.6 - Administrative change - Change in ATC
Code/ATC Vet Code
C.I.4, Update of the SmPC in section 4.5 in
order to add drug-drug interaction information
with P-gp, BCRP, CYP2D6, substrates (digoxin,
rosuvastatin, and dextromethorphan), based on
final results from study CPKC412A2121, a Phase
1, open-label, drug-drug interaction study,
listed as category 3 study in the RMP; section
5.2 of the SmPC and the Package Leaflet is
updated accordingly. (MEA 005.3)
C.I.4, Update of the SmPC in section 4.5 in
order to add drug-drug interaction information
with CYP2B6, CYP2C8, CYP3A4 substrates,
based on final results from study
CPKC412A2122, a Phase 1, open-label, drug-
drug interaction study, listed as category 3
study in the RMP; section 5.2 of the SmPC and
the Package Leaflet is updated accordingly.
(MEA 007.2)
C.I.4 Update of the SmPC in section 4.5 in order
to add drug-drug interaction information with
oral contraceptives, and section 4.6 to update
information on pregnancy and contraception
based on final results from study
CPKC412A2123, a Phase 1, open-label, drug-
drug interaction study, listed as category 3
study in the RMP; the Package Leaflet is
updated accordingly. (MEA 008.2)
C.I.4 Update of the SmPC in section 5.2 in order
to update pharmacokinetic information on
OATP1B1 transporters based on final results
from PBPK modelling study DMPK R2000528
listed as category 3 studies in the RMP (MEA
009);
C.I.4 Update of the SmPC in section 4.2 in order
to amend posology instructions, section 4.4 to
amend an existing warning and section 5.2 to
update pharmacokinetic information for patients
with severe hepatic impairment, based on final

EMA/CHMP/625004/2021 Page 33/67

results from study CPKC412A2116 listed as a
category 3 study in the RMP. This is an open
label, multiple dose study to evaluate the PK of
midostaurin in subjects with mild, moderate and
severe hepatic impairment compared to
matched healthy subjects; (MEA010)
The RMP version 6.0 has also been submitted.
In addition, MAH takes this opportunity to
introduce minor changes to edit the wording
related to the ethanol excipient in the Package
Leaflet, according the Annex to the European
Commission guideline on ‘Excipients in the
labelling and package leaflet of medicinal
products for human use' (SANTE-2017-11668),
by rounding the volume of alcohol to the next
integer number, i.e. from 16.9 to 17 ml.
The requested group of variations proposed
amendments to the Summary of Product
Characteristics and Package Leaflet and to the
Risk Management Plan (RMP).”
Request for Supplementary Information adopted
on 24.06.2021.

TECFIDERA - dimethyl fumarate - Request for supplementary information adopted

EMEA/H/C/002601/II/0069/G with a specific timetable.
Biogen Netherlands B.V., Rapporteur: Martina
Weise, PRAC Rapporteur: Martin Huber, “C.I.4
type II variation: Update of section 4.8 of the
SmPC in order to add rhinorrhoea to the list of
adverse drug reactions (ADRs) with frequency
unknown based on a systematic review of
information from clinical and non-clinical
studies, post-marketing data and scientific
literature. The Package Leaflet has been
updated accordingly.
C.I.4 type II variation: Update of sections 4.4,
4.8 and 5.1 of the SmPC in order to update
efficacy and safety information based on final
results from study 109MS303 (ENDORSE) listed
as a category 3 study in the RMP. This is a
dose-blind, multicenter, extension study to
determine the long-term safety and efficacy of
two doses of BG00012 monotherapy in subjects
with Relapsing-Remitting Multiple Sclerosis. The
RMP version 11.1 has also been submitted.”
Request for Supplementary Information adopted
on 28.10.2021, 02.09.2021, 08.07.2021,
06.05.2021, 14.01.2021.

Tremfya - guselkumab - Request for supplementary information adopted

EMEA/H/C/004271/II/0031 with a specific timetable.

EMA/CHMP/625004/2021 Page 34/67

Janssen-Cilag International N.V., Rapporteur:
Agnes Gyurasics, PRAC Rapporteur: Brigitte
Keller-Stanislawski, “C.I.4 Update of the
sections 4.8 and 5.1 of the SmPC based on the
2-year data from the psoriatic arthritis Phase 3
clinical study CNTO1959PSA3002 and to remove
this study as an additional PV activity from the
EU RMP. The RMP version 8.2 has also been
submitted.”
Request for Supplementary Information adopted
on 28.10.2021.

Trogarzo - ibalizumab - Positive Opinion adopted by consensus on

EMEA/H/C/004961/II/0015 28.10.2021. The Icelandic and Norwegian CHMP
Theratechnologies Europe Limited, Rapporteur: Members were in agreement with the CHMP
Johann Lodewijk Hillege, PRAC Rapporteur: recommendation.
David Olsen, “Submission of an updated RMP
version 2.0 in order to reflect the new timelines
of the PROMISE study and to align the
information included in the RMP with the latest
PSUR. As the PROMISE study is a condition of
the Trogarzo marketing authorisation, the
delayed start date results in a change to Annex
II of the marketing authorisation. The date for
providing the final study report is changing .”
Opinion adopted on 28.10.2021.
Request for Supplementary Information adopted
on 30.09.2021.

WS2134 Positive Opinion adopted by consensus on

OPDIVO-EMEA/H/C/003985/WS2134/ 28.10.2021. The Icelandic and Norwegian CHMP
0109 Members were in agreement with the CHMP
Yervoy-EMEA/H/C/002213/WS2134/0091 recommendation.
Bristol-Myers Squibb Pharma EEIG, Lead
Rapporteur: Paula Boudewina van Hennik, Lead
PRAC Rapporteur: Brigitte Keller-Stanislawski,
“Update of sections 4.2, 4.8 and 5.1 of the
SmPC based on final results from study
CA209908; this is a Phase Ib/II clinical trial of
nivolumab monotherapy and nivolumab in
combination with ipilimumab in paediatric
subjects with high grade primary CNS
malignancies; The RMP version 22.4 for Opdivo
has also been submitted.”
Opinion adopted on 28.10.2021.

WS2153
OPDIVO-EMEA/H/C/003985/WS2153/
0111
Yervoy-EMEA/H/C/002213/WS2153/0093
Bristol-Myers Squibb Pharma EEIG, Lead
Rapporteur: Paula Boudewina van Hennik, Lead

EMA/CHMP/625004/2021 Page 35/67

PRAC Rapporteur: Brigitte Keller-Stanislawski,
“Update of sections 4.2 and 6.6 of the SmPC to
change the infusion time for ipilimumab when
used as monotherapy or in combination with
nivolumab in the melanoma indications; the
Package Leaflet for Yervoy is updated
accordingly. The RMP versions 34.0 for Yervoy
and 26.0 for Opdivo have also been submitted.
In addition, an administrative update in Annex
II of Yervoy is introduced.”

B.5.4. PRAC assessed procedures

PRAC Led Positive Opinion adopted by consensus on

Afinitor - everolimus - 28.10.2021. The Icelandic and Norwegian CHMP
EMEA/H/C/001038/II/0076 Members were in agreement with the CHMP
Novartis Europharm Limited, Rapporteur: Janet recommendation.
Koenig, PRAC Rapporteur: Martin Huber, PRAC-
CHMP liaison: Janet Koenig, “Update of the
SmPC section 4.8 to include Lymphoedema as
an adverse drug reaction with the frequency
common based on the post-marketing data as
requested by the PRAC. The PL is updated
accordingly.”
Opinion adopted on 28.10.2021.

PRAC Led Positive Opinion adopted by consensus on

Azarga - brinzolamide / timolol - 28.10.2021. The Icelandic and Norwegian CHMP
EMEA/H/C/000960/II/0045 Members were in agreement with the CHMP
Novartis Europharm Limited, Rapporteur: Sinan recommendation.
B. Sarac, PRAC Rapporteur: Anette Kirstine
Stark, PRAC-CHMP liaison: Sinan B. Sarac,
“Update to the current risk management plan
(Version 3.0) to remove important identified
risks (Respiratory disorders, Cardiovascular
disorders, Corneal decompensation and
Metabolic acidosis), Important potential risk
(Long term use of preserved eye drops) and
Missing information (Use in paediatric patients)”
Opinion adopted on 28.10.2021.
Request for Supplementary Information adopted
on 08.07.2021.

PRAC Led Positive Opinion adopted by consensus on

Eylea - aflibercept - 28.10.2021. The Icelandic and Norwegian CHMP
EMEA/H/C/002392/II/0075 Members were in agreement with the CHMP
Bayer AG, Rapporteur: Alexandre Moreau, PRAC recommendation.
Rapporteur: Nathalie Gault, PRAC-CHMP liaison:
Alexandre Moreau, “Submission of this type II
variation as response to commitment
undertaken in procedure II/68 covering the

EMA/CHMP/625004/2021 Page 36/67

following elements:
1) validation of a follow-up questionnaire on
Intraocular pressure (IOP) increase,
2) simplification of the educational material
(prescriber guide and injection video) based on
the data being collected and after the
consultation with the panel of ophthalmologists,
3) RMP submission to include follow-up
questionnaire on IOP increase and timing of IOP
increase report submission”
Opinion adopted on 28.10.2021.
Request for Supplementary Information adopted
on 02.09.2021.

PRAC Led Positive Opinion adopted by consensus on

Fampyra - fampridine - 28.10.2021. The Icelandic and Norwegian CHMP
EMEA/H/C/002097/II/0049 Members were in agreement with the CHMP
Biogen Netherlands B.V., Rapporteur: Johann recommendation.
Lodewijk Hillege, PRAC Rapporteur: Liana
Gross-Martirosyan, PRAC-CHMP liaison: Johann
Lodewijk Hillege, “Following a PSUR 10
assessment, update to section 4.8 of the SmPC
to include new symptoms of trigeminal
neuralgia. The package leaflet to be updated
accordingly. The Marketing authorisation holder
(MAH) introduced further editorial updates
including bringing SmPC template to version
10.2 and updating contact details of the local
representatives.”
Opinion adopted on 28.10.2021.
Request for Supplementary Information adopted
on 08.07.2021.

PRAC Led Positive Opinion adopted by consensus on

Hemlibra - emicizumab - 28.10.2021. The Icelandic and Norwegian CHMP
EMEA/H/C/004406/II/0026 Members were in agreement with the CHMP
Roche Registration GmbH, Rapporteur: recommendation.
Alexandre Moreau, PRAC Rapporteur: Amelia
Cupelli, PRAC-CHMP liaison: Armando
Genazzani, “Update of section 4.8 of the SmPC
to include new data related to hypersensitivity,
in compliance with the PRAC recommendation
following the assessment of
PSUSA/00010668/202011. The PIL is updated in
accordance with the changes to the SmPC.”
Opinion adopted on 28.10.2021.

PRAC Led Positive Opinion adopted by consensus on

Lojuxta - lomitapide - 28.10.2021. The Icelandic and Norwegian CHMP
EMEA/H/C/002578/II/0047 Members were in agreement with the CHMP
Amryt Pharmaceuticals DAC, Rapporteur: recommendation.
Johann Lodewijk Hillege, PRAC Rapporteur:

EMA/CHMP/625004/2021 Page 37/67

Menno van der Elst, PRAC-CHMP liaison: Johann
Lodewijk Hillege, “Introduction of an enhanced
pharmacovigilance system to evaluate the
occurrence and outcomes of pregnancy in
females of reproductive potential treated with
lomitapide who decide to continue the
pregnancy following advice from a
teratologist/clinician, replacing the currently
agreed Pregnancy Exposure Register (PER),
which is listed as part of the specific obligations
in the Annex II. The RMP version 6.5 has also
been submitted. In addition, the MAH took the
opportunity to introduce minor administrative
changes.”
Opinion adopted on 28.10.2021.
Request for Supplementary Information adopted
on 10.06.2021.

PRAC Led Request for supplementary information adopted

Moventig - naloxegol - with a specific timetable.
EMEA/H/C/002810/II/0034
Kyowa Kirin Holdings B.V., Rapporteur:
Christophe Focke, PRAC Rapporteur: Rhea
Fitzgerald, PRAC-CHMP liaison: Peter Kiely,
“C.I.13: Submission of the final report from the
observational Post Authorisation Safety Study
(PASS)- Drug Utilisation in Selected European
Populations (D3820R00006), listed as a
category 3 study in the RMP. The RMP version
7.0 has also been submitted.”
Request for Supplementary Information adopted
on 28.10.2021.

PRAC Led Request for supplementary information adopted

Opsumit - macitentan - with a specific timetable.
EMEA/H/C/002697/II/0042, Orphan
Janssen-Cilag International N.V., Rapporteur:
Maria Concepcion Prieto Yerro, PRAC
Rapporteur: Eva A. Segovia, PRAC-CHMP
liaison: Maria Concepcion Prieto Yerro, “Type II
C.I.11 variation to update the risk management
plan to v12.1 and update to the Product
Information based on the outcome of the PRAC
assessment of
EMEA/H/C/PSUSA/00010115/202010:
- The controlled distribution system and
Prescriber Kit (SmPC, prescribing check list and
HCP brochure) is being removed as additional
risk minimisation measures (aRMM) in the RMP
and in the product information Annex II.D. Only
the patient alert card is remaining as an aRMM.

EMA/CHMP/625004/2021 Page 38/67

- Off-label use is being removed from the list of
safety concerns.
- “Elderly patients aged over 75 years”,
"patients with moderate to severe hepatic
impairment” and “Patients with severe renal
impairment and/ or undergoing dialysis” are
being removed as missing information.
- The MAH has also taken the opportunity to
include in the RMP Annex 4, the updated
Specific Follow-up Questionnaires Forms
(pregnancies, menstrual disorders, and ovarian
cysts) due to revision of internal company
template.
In addition, the MAH has taken this opportunity
to update the formatting of the headings of the
product information (annex I II and III) in line
with the latest QRD template.”
Request for Supplementary Information adopted
on 28.10.2021.

PRAC Led Request for supplementary information adopted

PecFent - fentanyl - with a specific timetable.
EMEA/H/C/001164/II/0054
Kyowa Kirin Holdings B.V., Rapporteur: Janet
Koenig, PRAC Rapporteur: Martin Huber, PRAC-
CHMP liaison: Janet Koenig, “Submission of an
updated RMP (version 7.1) in line with the
outcome of the last PSUR single assessment
(PSUSA) procedure (PSUSA 00001369/202004)
finalised in January 2021 in order to update the
key messages of the educational materials in
line with Instanyl (fentanyl). As a result, Annex
II-D on ‘Conditions or restrictions with regard to
the safe and effective use of the medicinal
product’ is updated accordingly. Finally, the
MAH took the opportunity to bring the RMP in
line with revision 2 of GVP module V on ‘Risk
management systems’ and the product
information in line with the latest quality review
of documents (QRD) template (version 10.2).
The requested variation proposed amendments
to the Annex II and to the Risk Management
Plan (RMP).”
Request for Supplementary Information adopted
on 28.10.2021.

PRAC Led Positive Opinion adopted by consensus on

Spikevax - COVID-19 mRNA vaccine 28.10.2021. The Icelandic and Norwegian CHMP
(nucleoside-modified) - Members were in agreement with the CHMP
EMEA/H/C/005791/II/0015/G recommendation.
Moderna Biotech Spain, S.L., Rapporteur: Jan

EMA/CHMP/625004/2021 Page 39/67

Mueller-Berghaus, PRAC Rapporteur: Hans
Christian Siersted, PRAC-CHMP liaison: Sinan B.
Sarac, “Grouped variation to address PRAC
requests raised in the 3rd Spikevax Monthly
Safety Summary Report (MSSR) procedure
(EMEA/H/C/005791/MEA/011.2):
- Update of section 4.8 of the SmPC to include
details regarding time to onset and duration of
the delayed injection site reactions. The
Package Leaflet is updated accordingly.
- Update of section 4.8 of the SmPC to include
“diarrhoea” as an adverse reaction, with the
frequency ‘Common’. The Package Leaflet is
updated accordingly.
In addition, the Marketing Authorisation Holder
(MAH) took the opportunity to make minor
editorial changes.”
Opinion adopted on 28.10.2021.
Request for Supplementary Information adopted
on 02.09.2021, 08.07.2021.

PRAC Led Request for supplementary information adopted

Spikevax - COVID-19 mRNA vaccine with a specific timetable.
(nucleoside-modified) -
EMEA/H/C/005791/II/0022
Moderna Biotech Spain, S.L., Rapporteur: Jan
Mueller-Berghaus, PRAC Rapporteur: Hans
Christian Siersted, PRAC-CHMP liaison: Sinan B.
Sarac, “Submission of an updated RMP version
2.0 to include clinical safety data from study
mRNA-1273 P203 (NCT04649151), a Phase 2/3,
randomised, observer-blind, placebo-controlled
study evaluating the safety, reactogenicity, and
effectiveness of the mRNA-1273 vaccine in
healthy adolescents aged ≥ 12 to < 18 years.”
Request for Supplementary Information adopted
on 28.10.2021, 02.09.2021.

PRAC Led Request for supplementary information adopted

Spikevax - COVID-19 mRNA vaccine with a specific timetable.
(nucleoside-modified) -
EMEA/H/C/005791/II/0028
Moderna Biotech Spain, S.L., Rapporteur: Jan
Mueller-Berghaus, PRAC Rapporteur: Hans
Christian Siersted, PRAC-CHMP liaison: Sinan B.
Sarac, “Submission of an updated RMP version
2.1 to include myocarditis and pericarditis as an
important identified risk, as requested by PRAC
as an outcome of the myocarditis and
pericarditis signal assessment procedure.”
Request for Supplementary Information adopted

EMA/CHMP/625004/2021 Page 40/67

on 28.10.2021, 02.09.2021.

PRAC Led Positive Opinion adopted by consensus on

Toviaz - fesoterodine - 28.10.2021. The Icelandic and Norwegian CHMP
EMEA/H/C/000723/II/0062 Members were in agreement with the CHMP
Pfizer Europe MA EEIG, Rapporteur: Maria recommendation.
Concepcion Prieto Yerro, PRAC Rapporteur:
Maria del Pilar Rayon, PRAC-CHMP liaison: Maria
Concepcion Prieto Yerro, “Submission of an
updated RMP version 10.0 in order to align the
important identified risks, important potential
risks, and missing information with the new
Guideline on good pharmacovigilance practice
(GVP) Module V - Risk management systems
(Revision 2.0), and to address the PSUR PRAC
recommendation
(EMEA/H/C/PSUSA/00001387/202004). RMP
Version 10.0 is accepted.”
Opinion adopted on 28.10.2021.

PRAC Led Request for supplementary information adopted

Vaxzevria - COVID 19 Vaccine (ChAdOx1 S with a specific timetable.
[recombinant]) -
EMEA/H/C/005675/II/0038
AstraZeneca AB, Rapporteur: Sol Ruiz, PRAC
Rapporteur: Jean-Michel Dogné, PRAC-CHMP
liaison: Christophe Focke, “Submission of the
final report from study MS1222-0003
''Assessment of anti-PF4 antibodies prior to, and
following, vaccination with AZD1222" listed as a
category 3 study in the RMP. This is a study
where sera of vaccinated individuals in study
D8110C00001 are tested to elucidate whether
vaccination with Vaxzevria leads to increased
levels of circulating anti-PF4 antibodies, a key
component of the hypothesized mechanism
underlying thrombosis with thrombocytopenia
syndrome (TTS).”
Request for Supplementary Information adopted
on 28.10.2021.

PRAC Led Request for supplementary information adopted

Vaxzevria - COVID 19 Vaccine (ChAdOx1 S with a specific timetable.
[recombinant]) -
EMEA/H/C/005675/II/0040
AstraZeneca AB, Rapporteur: Sol Ruiz, PRAC
Rapporteur: Jean-Michel Dogné, PRAC-CHMP
liaison: Christophe Focke, “Submission of an
updated RMP version 4.1 in order to:
- Add 'Thrombosis in combination with
thrombocytopenia' as an important potential
risk, as per PRAC outcome of Signal Assessment

EMA/CHMP/625004/2021 Page 41/67

procedure on Immune Thrombocytopenia dated
08 July 2021 (EPITT no: 19678);
- Add Acute Macular neuroretinopathy / Acute
Macular outer retinopathy, Paracentral acute
middle maculopathy and Parasthesia and
dysaesthesia in the list of AESIs, as per PRAC
outcome of Signal Assessment procedure on
Acute Macular Outer Retinopathy dated 08 July
2021 (EPITT no: 19703);
- Remove the Enhanced active surveillance
(EAS) studies D8111R00003 [EU],
D8110R00001 [US], D8111C00004 [UK]);
- Update the important potential risk of
`Nervous system disorders, including immune-
mediated neurological conditions' to reflect
recent label updates regarding Guillain-Barré
syndrome (IB/0034), as per PRAC outcome of
Vaxzevria 4th Monthly Summary Safety Update
(MEA 027.3), dated 26 June 2021;
- Add the UK effectiveness study
(D8111R00007), as per CHMP conclusion from
MEA 010.1 dated 22 July 2021;
- Addition of a study D8111R00010 to assess
the relationship between the exposure to
COVID-19 vaccines and risk of thrombotic
thrombocytopenia syndrome.”
Request for Supplementary Information adopted
on 28.10.2021.

PRAC Led Positive Opinion adopted by consensus on

XGEVA - denosumab - 28.10.2021. The Icelandic and Norwegian CHMP
EMEA/H/C/002173/II/0078 Members were in agreement with the CHMP
Amgen Europe B.V., Rapporteur: Kristina recommendation.
Dunder, PRAC Rapporteur: Ulla Wändel Liminga,
PRAC-CHMP liaison: Kristina Dunder,
“Submission of the final report from study
20101102 “Osteonecrosis of the Jaw (ONJ) Case
Registry”, listed as a category 3 study in the
RMP. This is an observational PASS with the
primary objective to estimate the rate and
describe the time course of resolution of ONJ, in
subjects 18 years of age with cancer who had
newly diagnosed, positively adjudicated ONJ.”
Opinion adopted on 28.10.2021.

PRAC Led Positive Opinion adopted by consensus on

Zostavax - varicella vaccine (live) - 28.10.2021. The Icelandic and Norwegian CHMP
EMEA/H/C/000674/II/0138 Members were in agreement with the CHMP
MSD Vaccins, Rapporteur: Jan Mueller- recommendation.
Berghaus, PRAC Rapporteur: Brigitte Keller-
Stanislawski, PRAC-CHMP liaison: Jan Mueller-

EMA/CHMP/625004/2021 Page 42/67

Berghaus, “Submission of an updated RMP
version 9.1 to reflect the completion of this
long-term effectiveness study (Protocol 024)
and to align the RMP template with EMA GVP
Module V (rev 2) guidance.”
Opinion adopted on 28.10.2021.

PRAC Led Positive Opinion adopted by consensus on

WS1919 28.10.2021. The Icelandic and Norwegian CHMP
Lyrica-EMEA/H/C/000546/WS1919/0109 Members were in agreement with the CHMP
Pregabalin Pfizer- recommendation.
EMEA/H/C/003880/WS1919/0038
Upjohn EESV, Lead Rapporteur: Johann
Lodewijk Hillege, Lead PRAC Rapporteur: Liana
Gross-Martirosyan, PRAC-CHMP liaison: Johann
Lodewijk Hillege, “Submission of an updated
RMP (version 13.2) to include results from
recently completed PASS studies, namely: 1)
study A0081359: a population-based cohort
study of pregabalin to characterize pregnancy
outcomes; 2) study A0081106: a 12-month
open-label study to evaluate the safety and
tolerability of pregabalin as adjunctive therapy
in paediatric subjects 1 month to 16 years of
age with partial onset seizures and paediatric
and adult subjects 5 to 65 years of age with
primary generalized tonic-clonic seizures; 3)
study A0081042: a double-blind, placebo-
controlled, parallel-group, multicentre study of
the efficacy and safety of pregabalin as
adjunctive therapy in children 1 month through
<4 years of age with partial onset seizures; 4)
study A0081105: a randomized, double-blind,
placebo-controlled, parallel group, multicentre
trial of pregabalin as adjunctive therapy in
paediatric and adult subjects with primary
generalized tonic-clonic seizures. In addition,
information on A0081096: a prospective
randomized 12-week controlled study of visual
field change in subjects with partial seizures
receiving pregabalin or placebo has been
updated as well as A0081365: a phase 4,
randomised, double-blind, double-dummy,
placebo- and active-controlled, single-dose, six-
way crossover study to evaluate the potential
for abuse with pregabalin. However, further
issues noted with the RMP should be updated at
the next regulatory opportunity.
In the light of the results from the pregnancy
outcomes study, section 4.6 of the SmPC is
being updated concerning the risks of

EMA/CHMP/625004/2021 Page 43/67

pregabalin treatment during pregnancy,
indicating that women of childbearing potential
have to use effective contraception, pregabalin
may cross the human placenta and the
description of major congenital malformations
(MCM). In addition, section 4.4 is updated to
highlight that pregabalin should not be used
during pregnancy unless clearly necessary and
women of childbearing potential have to use
effective contraception based on the new data
on MCM.”
Opinion adopted on 28.10.2021.
Request for Supplementary Information adopted
on 10.06.2021, 01.10.2020.

PRAC Led Request for supplementary information adopted

WS2151 with a specific timetable.
Aflunov-EMEA/H/C/002094/WS2151/
0071
Foclivia-EMEA/H/C/001208/WS2151/
0068
Seqirus S.r.l, Lead Rapporteur: Armando
Genazzani, Lead PRAC Rapporteur: Amelia
Cupelli, PRAC-CHMP liaison: Armando
Genazzani, “Submission of an updated RMP
version 3.9 in order to align safety concerns for
both products AFLUNOV and FOCLIVIA. Module
on 'Epidemiology of the indication and target
population' and section on 'use in pregnancy
and lactation' are updated. Some potential risks
have been reclassified following the definition as
per GVP Module V rev.2. Reference to adverse
drug reaction follow-up forms for routine
pharmacovigilance activity are removed.”
Request for Supplementary Information adopted
on 28.10.2021.

B.5.5. CHMP-CAT assessed procedures

Abecma - idecabtagene vicleucel -

EMEA/H/C/004662/II/0001/G, Orphan,
ATMP
Celgene Europe B.V., Rapporteur: Rune Kjeken,
CHMP Coordinator: Ingrid Wang

Abecma - idecabtagene vicleucel -

EMEA/H/C/004662/II/0002, Orphan,
ATMP
Celgene Europe B.V., Rapporteur: Rune Kjeken,
CHMP Coordinator: Ingrid Wang

EMA/CHMP/625004/2021 Page 44/67

Imlygic - talimogene laherparepvec -
EMEA/H/C/002771/II/0047/G, ATMP
Amgen Europe B.V., Rapporteur: Heli Suila,
CHMP Coordinator: Johanna Lähteenvuo

Zolgensma - onasemnogene abeparvovec -

EMEA/H/C/004750/II/0019/G, Orphan,
ATMP
Novartis Gene Therapies EU Limited,
Rapporteur: Carla Herberts, CHMP Coordinator:
Johann Lodewijk Hillege

B.5.6. CHMP-PRAC-CAT assessed procedures

B.5.7. PRAC assessed ATMP procedures

B.5.8. Unclassified procedures and worksharing procedures of type I variations

WS2060 Positive Opinion adopted by consensus on

HyQvia-EMEA/H/C/002491/WS2060/0071 21.10.2021. The Icelandic and Norwegian CHMP
Kiovig-EMEA/H/C/000628/WS2060/0109 Members were in agreement with the CHMP
Takeda Manufacturing Austria AG, Lead recommendation.
Rapporteur: Jan Mueller-Berghaus
Opinion adopted on 21.10.2021.
Request for Supplementary Information adopted
on 10.06.2021.

WS2096 Positive Opinion adopted by consensus on

Comtess-EMEA/H/C/000170/WS2096/ 21.10.2021. The Icelandic and Norwegian CHMP
0061 Members were in agreement with the CHMP
Entacapone Orion-EMEA/H/C/002440/ recommendation.
WS2096/0020
Orion Corporation, Lead Rapporteur: Outi Mäki-
Ikola, “To update sections 2 and 4.4. of the
SmPC, section 3 of the Labelling and section 2
of the PL to add a statement warning for the
excipient sodium. The proposed update is not in
accordance with the Annex of the “Excipients in
the labelling and package leaflet of medicinal
products”.
The marketing authorisation holder took the
opportunity to align the PI to the latest QRD
template (version 10.2). The details of the local
representatives are updated for Comtess in
United Kingdom (Northern Ireland) and for
Entacapone Orion in Germany, Greece, Ireland,
Poland and United Kingdom (Northern Ireland).”
Opinion adopted on 21.10.2021.

WS2112 Positive Opinion adopted by consensus on

Hexacima-EMEA/H/C/002702/WS2112/ 28.10.2021. The Icelandic and Norwegian CHMP

EMA/CHMP/625004/2021 Page 45/67

0119 Members were in agreement with the CHMP
Hexyon-EMEA/H/C/002796/WS2112/ recommendation.
0123
Sanofi Pasteur, Lead Rapporteur: Jan Mueller-
Berghaus
Opinion adopted on 28.10.2021.
Request for Supplementary Information adopted
on 02.09.2021.

WS2116/G
Kivexa-EMEA/H/C/000581/WS2116/
0092/G
Triumeq-EMEA/H/C/002754/WS2116/
0096/G
Trizivir-EMEA/H/C/000338/WS2116/
0126/G
Ziagen-EMEA/H/C/000252/WS2116/
0121/G
ViiV Healthcare B.V., Lead Rapporteur: Filip
Josephson
Request for Supplementary Information adopted
on 09.09.2021.

WS2128/G
Eucreas-EMEA/H/C/000807/WS2128/
0090/G
Icandra-EMEA/H/C/001050/WS2128/
0093/G
Zomarist-EMEA/H/C/001049/WS2128/
0092/G
Novartis Europharm Limited, Lead Rapporteur:
Kristina Dunder

WS2137 Positive Opinion adopted by consensus on

Relvar Ellipta-EMEA/H/C/002673/ 21.10.2021. The Icelandic and Norwegian CHMP
WS2137/0050 Members were in agreement with the CHMP
Revinty Ellipta-EMEA/H/C/002745/ recommendation.
WS2137/0048
GlaxoSmithKline (Ireland) Limited, Lead
Rapporteur: Maria Concepcion Prieto Yerro, “The
marketing authorisation holder took the
opportunity to align the PI to the latest QRD
template (version 10.2).
To amend the exposure multiple for the no-
effect level seen in the carcinogenicity study in
rats with VI following an error.
In addition the MAH is updating the list of local
representatives in BG, CY, EE, EL, FI, HU, HR,
LT, LV, MT, RO, SI, SK, UK(NI).
The MAH has also amended the Revinty EN
annexes with regards to the local representative
details in ES, IT, FR, DE and PT as an error had

EMA/CHMP/625004/2021 Page 46/67

been identified.”
Opinion adopted on 21.10.2021.

WS2143
HBVAXPRO-EMEA/H/C/000373/
WS2143/0072
Vaxelis-EMEA/H/C/003982/WS2143/0089
MCM Vaccine B.V., Lead Rapporteur: Christophe
Focke

WS2167
Aflunov-EMEA/H/C/002094/WS2167/
0073
Foclivia-EMEA/H/C/001208/WS2167/
0070
Seqirus S.r.l, Lead Rapporteur: Armando
Genazzani, “To change the order of addition of
the monovalent antigens during the formulation
of the finished product.”

WS2176 Positive Opinion adopted by consensus on

Enurev Breezhaler- 28.10.2021. The Icelandic and Norwegian CHMP
EMEA/H/C/002691/WS2176/0039 Members were in agreement with the CHMP
Seebri Breezhaler- recommendation.
EMEA/H/C/002430/WS2176/0039
Tovanor Breezhaler-
EMEA/H/C/002690/WS2176/0043
Novartis Europharm Limited, Lead Rapporteur:
Sinan B. Sarac, “To update the PI for Seebri
Breezhaler (glycopyrronium bromide) and its
two duplicates, Enurev Breezhaler and Tovanor
Breezhaler in line with current QRD template
v10.2, Rev. 1 and QRD template v10.1 as
follows:
- Package leaflet is updated to include Northern
Ireland in the list of the local representatives of
the Marketing Authorisation Holder (QRD v10.2)
- ANNEX II (C and D sections) and Labelling are
updated in line with the QRD template v10.1.
The MAH also updated section 4.4 (subsection
'Excipients') of the SmPC (Annex I) to change
the word from “the Lapp” to “total” to align with
the latest European Commission guideline on
`Excipients in the labelling and package leaflet
of medicinal products for human use' (SANTE-
2017-11668), dated 22-Nov-2019.
In addition, the MAH has taken the opportunity
to update the Instructions for use (IFU) in
section 6.6 of the SmPC (Annex I) and also at
the end of the Package leaflet.”
Opinion adopted on 28.10.2021.

EMA/CHMP/625004/2021 Page 47/67

B.5.9. Information on withdrawn type II variation / WS procedure

B.5.10. Information on type II variation / WS procedure with revised timetable

B.6. START OF THE PROCEDURES TIMETABLES FOR INFORMATION

B.6.1. Start of procedure for New Applications: timetables for information

sutimlimab - EMEA/H/C/005776, Orphan

Genzyme Europe BV, treatment of haemolysis in
adult patients with cold agglutinin disease (CAD)

gozetotide - EMEA/H/C/005488
indicated for the identification of prostate-
specific membrane antigen (PSMA)-positive
lesions after radiolabelling with gallium-68

bardoxolone methyl / bardoxolone methyl

- EMEA/H/C/005869, Orphan
Reata Ireland Limited, treatment of chronic
kidney disease

lutetium (177lu) vipivotide tetraxetan -

EMEA/H/C/005483
treatment of prostate-specific membrane
antigen (PSMA)-positive metastatic castration-
resistant prostate cancer (mCRPC)

pegfilgrastim - EMEA/H/C/005587
treatment of neutropenia

mosunetuzumab - EMEA/H/C/005680 Accelerated review

refractory follicular lymphoma (FL)

tirzepatide - EMEA/H/C/005620
treatment of adults with type 2 diabetes
mellitus

plerixafor - EMEA/H/C/005943
treatment of lymphoma and multiple myeloma

ruxolitinib - EMEA/H/C/005843
treatment of non-segmental vitiligo

spesolimab - EMEA/H/C/005874
treatment of flares in adult patients with
generalised pustular psoriasis

teriflunomide - EMEA/H/C/005960
treatment of multiple sclerosis (MS)

deucravacitinib - EMEA/H/C/005755
treatment of moderate to severe plaque
psoriasis in adults who are candidates for

EMA/CHMP/625004/2021 Page 48/67

systemic therapy

bevacizumab - EMEA/H/C/005534
treatment of metastatic carcinoma of the colon
or rectum, metastatic breast cancer and
recurrence of platinum-sensitive epithelial
ovarian, fallopian tube or primary peritoneal
cancer.
First-line treatment of patients with
unresectable advanced, metastatic or recurrent
non-small cell lung cancer.
First-line treatment of patients with advanced
and/or metastatic renal cell cancer.

ganaxolone - EMEA/H/C/005825, Orphan Accelerated review

Marinus Pharmaceuticals Emerald Limited,
treatment of epileptic seizures associated with
cyclindependent kinase-like 5 deficiency
disorder (CDD)

loncastuximab tesirine -
EMEA/H/C/005685, Orphan
FGK Representative Service GmbH, treatment of
adult patients with relapsed or refractory large
B-cell lymphoma

B.6.2. Start of procedure for Extension application according to Annex I of Reg.

1234/2008): timetables for information

Calquence - acalabrutinib -
EMEA/H/C/005299/X/0009/G
AstraZeneca AB, Rapporteur: Filip Josephson,
PRAC Rapporteur: Nikica Mirošević Skvrce,
“Extension application to introduce a new
pharmaceutical form, film-coated tablet. The
active substance in the new formulation,
acalabrutinib maleate, is a free base equivalent
of acalabrutinib, the active substance used in
the hard capsules formulation.
A.6 - To change the ATC Code of acalabrutinib
from L01XE51 to L01EL02.”

COMIRNATY - tozinameran -
EMEA/H/C/005735/X/0077
BioNTech Manufacturing GmbH, Rapporteur:
Filip Josephson, Co-Rapporteur: Jean-Michel
Race, PRAC Rapporteur: Menno van der Elst,
“Extension application to add a new strength
(0.1 mg/ml). The new presentations are
indicated for children from 5 to 11 years of

EMA/CHMP/625004/2021 Page 49/67

age.”

B.6.3. Restart of procedure - responses received to Day 120 List of Questions timetables:
for information

betaine anhydrous - EMEA/H/C/005637

treatment of homocystinuria
List of Questions adopted on 22.04.2021.

difelikefalin - EMEA/H/C/005612
treatment of pruritus
List of Questions adopted on 22.07.2021.

teriparatide - EMEA/H/C/004932
Treatment of osteoporosis in postmenopausal
women and in men at increased risk of fracture
List of Questions adopted on 28.01.2021.

Mayzent - siponimod -
EMEA/H/C/004712/X/0007
Novartis Europharm Limited, Rapporteur: Sinan
B. Sarac, PRAC Rapporteur: Maria del Pilar
Rayon, “Extension application to add a new
strength of 1 mg film-coated tablet. The RMP
(version 3.0) is updated in accordance.”
List of Questions adopted on 16.09.2021.

Nucala - mepolizumab -
EMEA/H/C/003860/X/0042
GlaxoSmithKline Trading Services Limited,
Rapporteur: Peter Kiely, PRAC Rapporteur:
Brigitte Keller-Stanislawski, “Extension
application to introduce a new strength of 40
mg for Nucala solution for injection in a pre-
filled syringe for subcutaneous use to be used in
children aged 6 to 11 years.”
List of Questions adopted on 16.09.2021.

opicapone - EMEA/H/C/005782
treatment of Parkinson’s disease and motor
fluctuations
List of Questions adopted on 22.07.2021.

relugolix - EMEA/H/C/005353
treatment of adult patients with advanced
prostate cancer.
List of Questions adopted on 22.07.2021.

daridorexant - EMEA/H/C/005634
treatment of insomnia
List of Questions adopted on 22.07.2021.

EMA/CHMP/625004/2021 Page 50/67

teriparatide - EMEA/H/C/005827
treatment of osteoporosis
List of Questions adopted on 22.07.2021.

Yuflyma - adalimumab -
EMEA/H/C/005188/X/0005
Celltrion Healthcare Hungary Kft., Rapporteur:
Outi Mäki-Ikola, PRAC Rapporteur: Ulla Wändel
Liminga, “Extension application to introduce a
new strengths of 80 mg solution for injection.
Version 1.1 of the RMP has also been
submitted.”
List of Questions adopted on 16.09.2021.

Zejula - niraparib -
EMEA/H/C/004249/X/0029, Orphan
GlaxoSmithKline (Ireland) Limited, Rapporteur:
Ingrid Wang, PRAC Rapporteur: Jan Neuhauser,
“Extension application to introduce a new
pharmaceutical form (100 mg film-coated
tablet). The RMP (version 5.1) is updated in
accordance.”
List of Questions adopted on 14.10.2021.

B.6.4. Annual Re-assessments: timetables for adoption

Myalepta - metreleptin -
EMEA/H/C/004218/S/0023, Orphan
Amryt Pharmaceuticals DAC, Rapporteur: Karin
Janssen van Doorn, PRAC Rapporteur: Adam
Przybylkowski

Raxone - idebenone -
EMEA/H/C/003834/S/0029, Orphan
Santhera Pharmaceuticals (Deutschland) GmbH,
Rapporteur: John Joseph Borg, PRAC
Rapporteur: Amelia Cupelli

B.6.5. Renewals of Marketing Authorisations: timetables for adoption provided only if the
validation has been completed

Bosulif - bosutinib -
EMEA/H/C/002373/R/0051
Pfizer Europe MA EEIG, Rapporteur: Janet
Koenig, Co-Rapporteur: Blanca Garcia-Ochoa,
PRAC Rapporteur: Martin Huber

COVID-19 Vaccine Janssen - adenovirus

type 26 encoding the SARS-CoV-2 spike
glycoprotein - EMEA/H/C/005737/R/0023
Janssen-Cilag International N.V., Rapporteur:
Christophe Focke, PRAC Rapporteur: Ulla

EMA/CHMP/625004/2021 Page 51/67

Wändel Liminga

Deltyba - delamanid -
EMEA/H/C/002552/R/0052, Orphan
Otsuka Novel Products GmbH, Rapporteur:
Christophe Focke, PRAC Rapporteur: Laurence
de Fays

Dupixent - dupilumab -
EMEA/H/C/004390/R/0053
sanofi-aventis groupe, Rapporteur: Jan Mueller-
Berghaus, Co-Rapporteur: Peter Kiely, PRAC
Rapporteur: Kimmo Jaakkola

Efavirenz/Emtricitabine/Tenofovir
disoproxil Zentiva - efavirenz /
emtricitabine / tenofovir disoproxil -
EMEA/H/C/004250/R/0025
Zentiva k.s., Generic, Generic of Atripla,
Rapporteur: Tomas Radimersky, PRAC
Rapporteur: Martin Huber

Insulin lispro Sanofi - insulin lispro -

EMEA/H/C/004303/R/0013
sanofi-aventis groupe, Rapporteur: Outi Mäki-
Ikola, Co-Rapporteur: Martina Weise, PRAC
Rapporteur: Annika Folin

JEMPERLI - dostarlimab -
EMEA/H/C/005204/R/0004
GlaxoSmithKline (Ireland) Limited, Rapporteur:
Blanca Garcia-Ochoa, PRAC Rapporteur: Marcia
Sofia Sanches de Castro Lopes Silva

Kisqali - ribociclib -
EMEA/H/C/004213/R/0034
Novartis Europharm Limited, Rapporteur: Filip
Josephson, Co-Rapporteur: Blanca Garcia-
Ochoa, PRAC Rapporteur: Anette Kirstine Stark

Kyntheum - brodalumab -
EMEA/H/C/003959/R/0019
LEO Pharma A/S, Rapporteur: Johann Lodewijk
Hillege, Co-Rapporteur: Jan Mueller-Berghaus,
PRAC Rapporteur: Eva A. Segovia

Maviret - glecaprevir / pibrentasvir -

EMEA/H/C/004430/R/0048
AbbVie Deutschland GmbH & Co. KG,
Rapporteur: Jean-Michel Race, Co-Rapporteur:
Filip Josephson, PRAC Rapporteur: Ana Sofia
Diniz Martins

Natpar - parathyroid hormone -

EMEA/H/C/003861/R/0034, Orphan

EMA/CHMP/625004/2021 Page 52/67

Takeda Pharmaceuticals International AG,
Rapporteur: Karin Janssen van Doorn, Co-
Rapporteur: Agnes Gyurasics, PRAC Rapporteur:
Rhea Fitzgerald

OXERVATE - cenegermin -
EMEA/H/C/004209/R/0037, Orphan
Dompe farmaceutici S.p.A., Rapporteur: Maria
Concepcion Prieto Yerro, Co-Rapporteur: Peter
Kiely, PRAC Rapporteur: Jan Neuhauser

Pemazyre - pemigatinib -
EMEA/H/C/005266/R/0003, Orphan
Incyte Biosciences Distribution B.V.,
Rapporteur: Alexandre Moreau, Co-Rapporteur:
Janet Koenig, PRAC Rapporteur: Menno van der
Elst

Reagila - cariprazine -
EMEA/H/C/002770/R/0026
Gedeon Richter Plc., Rapporteur: Kristina
Dunder, Co-Rapporteur: Outi Mäki-Ikola, PRAC
Rapporteur: Ana Sofia Diniz Martins

Ucedane - carglumic acid -

EMEA/H/C/004019/R/0011
Eurocept International B.V., Generic, Generic of
Carbaglu, Rapporteur: Eleftheria Nikolaidi, PRAC
Rapporteur: Ana Sofia Diniz Martins

WAYLIVRA - volanesorsen -
EMEA/H/C/004538/R/0016, Orphan
Akcea Therapeutics Ireland Limited, Rapporteur:
Johann Lodewijk Hillege, Co-Rapporteur: Karin
Janssen van Doorn, PRAC Rapporteur: Martin
Huber

B.6.6. VARIATIONS – START OF THE PROCEDURE

Timetables for adoption provided that the validation has been completed.

B.6.7. Type II Variations scope of the Variations: Extension of indication

Enhertu - trastuzumab deruxtecan -

EMEA/H/C/005124/II/0012
Daiichi Sankyo Europe GmbH, Rapporteur:
Sinan B. Sarac, Co-Rapporteur: Paula
Boudewina van Hennik, PRAC Rapporteur:
Marcia Sofia Sanches de Castro Lopes Silva,
“Extension of indication to include monotherapy
treatment of adult patients with locally
advanced or metastatic HER2-positive gastric or
gastroesophageal junction (GEJ)

EMA/CHMP/625004/2021 Page 53/67

adenocarcinoma who have received a prior anti-
HER2-based regimen for Enhertu based on final
results from studies DS8201 A J202 (DESTINY
Gastric01) and DS8201-A-U205 (DESTINY
Gastric02); as a consequence, sections 4.1, 4.2,
4.4, 4.8, 5.1 and 5.2 of the SmPC are updated.
The Package Leaflet is updated in accordance.
In addition, changes regarding the dosing
recommendation for corticosteroid treatment
and the protection of the infusion bag from light
have been introduced. Version 1.1 of the RMP
has also been submitted.”
Request for 1 year of market protection for a
new indication (Article 14(11) of Regulation
(EC) 726/2004)

Hemlibra - emicizumab -
EMEA/H/C/004406/II/0027
Roche Registration GmbH, Rapporteur:
Alexandre Moreau, Co-Rapporteur: Jan Mueller-
Berghaus, PRAC Rapporteur: Amelia Cupelli,
“Extension of indication to include treatment of
adult and paediatric patients with haemophilia A
without factor VIII (FVIII) inhibitors who have
mild or moderate disease for whom prophylaxis
is clinically indicated. Consequently, sections
4.1, 4.8, 5.1 and 5.2 of the SmPC and section 1
of the package leaflet are updated. In addition,
section 4.2 is updated to make it clear that the
maintenance dose for Hemlibra applies from
week 5 of dosing. The PIL is updated
accordingly. Version 4.0 of the RMP has also
been submitted.”

IMCIVREE - setmelanotide -
EMEA/H/C/005089/II/0002/G, Orphan
Rhythm Pharmaceuticals Netherlands B.V.,
Rapporteur: Karin Janssen van Doorn, PRAC
Rapporteur: Michal Radik, “Group of variations
consisting of:
C.I.6.a - To add the new therapeutic indication
for the treatment of obesity and the control of
hunger associated with genetically confirmed
Bardet-Biedl syndrome (BBS). As a
consequence, sections 4.1, 4.2, 4.8, 5.1, 5.2
and 5.3 of the SmPC and sections 1, 3 and 4 of
the PL are updated accordingly. The updated
RMP version 1.0 has also been submitted.
C.I.6.a - To add the new therapeutic indication
for the treatment of obesity and the control of
hunger associated with genetically confirmed

EMA/CHMP/625004/2021 Page 54/67

Alström syndrome (AS). As a consequence,
sections 4.1, 4.2, 4.8, 5.1, 5.2 and 5.3 of the
SmPC and sections 1, 3 and 4 of the PL are
updated accordingly. The updated RMP version
1.0 has also been submitted.”

Keytruda - pembrolizumab -
EMEA/H/C/003820/II/0117
Merck Sharp & Dohme B.V., Rapporteur:
Armando Genazzani, Co-Rapporteur: Jan
Mueller-Berghaus, PRAC Rapporteur: Menno van
der Elst, “Extension of indication to include a
new indication for Keytruda, in combination with
chemotherapy, with or without bevacizumab, for
the treatment of persistent, recurrent, or
metastatic cervical cancer in adults; as a
consequence, sections 4.1 and 5.1 of the SmPC
are updated. The Package Leaflet is updated in
accordance. Version 38.1 of the RMP has also
been submitted.”

Lynparza - olaparib -
EMEA/H/C/003726/II/0051/G
AstraZeneca AB, Rapporteur: Alexandre Moreau,
Co-Rapporteur: Karin Janssen van Doorn, PRAC
Rapporteur: Amelia Cupelli, “Extension of
indication to include adjuvant treatment of
breast cancer for Lynparza (for tablets); as a
consequence, sections 4.1, 4.2, 4.5, 4.8 and 5.1
of the SmPC are updated. In addition, sections
4.8 of the SmPC for Lynparza hard capsules are
revised based on the updated safety data
analysis. The Package Leaflet is updated in
accordance. Version 23 of the RMP has also
been submitted.”

NovoSeven - eptacog alfa (activated) -

EMEA/H/C/000074/II/0116
Novo Nordisk A/S, Rapporteur: Paula Boudewina
van Hennik, Co-Rapporteur: Alexandre Moreau,
PRAC Rapporteur: Menno van der Elst,
“Extension of indication to include treatment of
severe postpartum haemorrhage for
NovoSeven. As a consequence, sections 4.1,
4.2, 4.4, 4.5, 4.8 and 5.1 of the SmPC are
updated. The Package Leaflet is also updated in
accordance. Version 8.0 of the RMP has also
been submitted.”

Reblozyl - luspatercept -
EMEA/H/C/004444/II/0009, Orphan
Bristol-Myers Squibb Pharma EEIG, Rapporteur:

EMA/CHMP/625004/2021 Page 55/67

Daniela Philadelphy, Co-Rapporteur: Ewa
Balkowiec Iskra, PRAC Rapporteur: Laurence de
Fays, “C.I.6 (Extension of indication)
Extension of indication in β-thalassaemia to
include adult patients with non-transfusion
dependent β-thalassaemia (NTDT) for Reblozyl;
as a consequence, sections 4.1, 4.2, 4.4, 4.8,
5.1 and 5.2 of the SmPC are updated. The
Package Leaflet is updated in accordance.
Version 1.1 of the RMP has also been submitted.
In addition, the Marketing authorisation holder
(MAH) took the opportunity to update the list of
local representatives in the Package Leaflet.”
Request for 1 year of market protection for a
new indication (Article 14(11) of Regulation
(EC) 726/2004)

B.6.8. CHMP assessed procedures scope: Pharmaceutical aspects

ADYNOVI - rurioctocog alfa pegol -

EMEA/H/C/004195/II/0024
Baxalta Innovations GmbH, Rapporteur: Andrea
Laslop

COMIRNATY - tozinameran - See B.6.8

EMEA/H/C/005735/II/0078/G
BioNTech Manufacturing GmbH, Rapporteur:
Filip Josephson

COMIRNATY - tozinameran -
EMEA/H/C/005735/II/0083/G
BioNTech Manufacturing GmbH, Rapporteur:
Filip Josephson

COVID-19 Vaccine Janssen - adenovirus

type 26 encoding the SARS-CoV-2 spike
glycoprotein -
EMEA/H/C/005737/II/0026/G
Janssen-Cilag International N.V., Rapporteur:
Christophe Focke

Cyramza - ramucirumab -
EMEA/H/C/002829/II/0044
Eli Lilly Nederland B.V., Rapporteur: Paula
Boudewina van Hennik

Elonva - corifollitropin alfa -

EMEA/H/C/001106/II/0062
Organon N.V., Rapporteur: Paula Boudewina
van Hennik

Emtricitabine/Tenofovir disoproxil Mylan -

emtricitabine / tenofovir disoproxil -

EMA/CHMP/625004/2021 Page 56/67

EMEA/H/C/004050/II/0019
Mylan S.A.S, Generic, Generic of Truvada,
Rapporteur: Romaldas Mačiulaitis

Fasenra - benralizumab -
EMEA/H/C/004433/II/0038/G
AstraZeneca AB, Rapporteur: Fátima Ventura

Fasenra - benralizumab -
EMEA/H/C/004433/II/0040
AstraZeneca AB, Rapporteur: Fátima Ventura

ProQuad - measles, mumps, rubella and

varicella vaccine (live) -
EMEA/H/C/000622/II/0154
MSD Vaccins, Rapporteur: Jan Mueller-Berghaus

Revestive - teduglutide -
EMEA/H/C/002345/II/0055, Orphan
Shire Pharmaceuticals Ireland Limited,
Rapporteur: Sinan B. Sarac

RoActemra - tocilizumab -
EMEA/H/C/000955/II/0104/G
Roche Registration GmbH, Rapporteur: Jan
Mueller-Berghaus

Supemtek - quadrivalent influenza vaccine

(recombinant, prepared in cell culture) -
EMEA/H/C/005159/II/0005/G
Sanofi Pasteur, Rapporteur: Jan Mueller-
Berghaus

Synagis - palivizumab -
EMEA/H/C/000257/II/0127/G
AstraZeneca AB, Rapporteur: Sinan B. Sarac

Thyrogen - thyrotropin alfa -

EMEA/H/C/000220/II/0109/G
Genzyme Europe BV, Rapporteur: Peter Kiely

Vaxchora - cholera vaccine, oral, live -

EMEA/H/C/003876/II/0009
Emergent Netherlands B.V., Rapporteur: Ingrid
Wang

Vaxzevria - COVID 19 Vaccine (ChAdOx1 S

[recombinant]) -
EMEA/H/C/005675/II/0050
AstraZeneca AB, Rapporteur: Sol Ruiz

Vaxzevria - COVID 19 Vaccine (ChAdOx1 S

[recombinant]) -
EMEA/H/C/005675/II/0051/G
AstraZeneca AB, Rapporteur: Sol Ruiz

EMA/CHMP/625004/2021 Page 57/67

VEYVONDI - vonicog alfa -
EMEA/H/C/004454/II/0020
Baxalta Innovations GmbH, Rapporteur: Jan
Mueller-Berghaus

Yuflyma - adalimumab -
EMEA/H/C/005188/II/0009/G
Celltrion Healthcare Hungary Kft., Rapporteur:
Outi Mäki-Ikola

ZABDENO - ebola vaccine (rDNA,

replication-incompetent) -
EMEA/H/C/005337/II/0006/G
Janssen-Cilag International N.V., Rapporteur:
Johann Lodewijk Hillege

WS2182/G
Fluenz Tetra-EMEA/H/C/002617/WS2182/
0110/G
Pandemic influenza vaccine H5N1
AstraZeneca-EMEA/H/C/003963/WS2182/
0045/G
AstraZeneca AB, Lead Rapporteur: Christophe
Focke

B.6.9. CHMP assessed procedures scope: Non-Clinical and Clinical aspects

Adtralza - tralokinumab -
EMEA/H/C/005255/II/0001
LEO Pharma A/S, Rapporteur: Jayne Crowe,
“C.I.4
Update of sections 4.5 and 5.2 of the SmPC in
order to add drug-drug interaction information
with cytochrome P450 and CYP substrates based
on final results from study ECZTRA 4 (LP0162-
1342). This is an open-label drug–drug
interaction trial to investigate the effects of
tralokinumab on the pharmacokinetics of
selected CYP substrates in adult subjects with
moderate-to-severe atopic dermatitis. In
addition, the MAH took the opportunity make
editorial changes to sections 4.8, 6.5 and 9 of
SmPC.”

Bimzelx - bimekizumab -
EMEA/H/C/005316/II/0002
UCB Pharma S.A., Rapporteur: Peter Kiely,
“C.I.4 - Update of section 5.1 of the SmPC in
order to update efficacy information based on
interim results from study PS0015; this is a
multicenter, randomized, double-blind, active
comparator controlled, parallel group study to

EMA/CHMP/625004/2021 Page 58/67

evaluate the efficacy and safety of bimekizumab
compared with secukinumab in adult study
participants with moderate to severe plaque
psoriasis. In addition, the MAH took the
opportunity to bring the PI in line with the latest
QRD template version 10.2.”

Cyramza - ramucirumab -
EMEA/H/C/002829/II/0043
Eli Lilly Nederland B.V., Rapporteur: Paula
Boudewina van Hennik, “Update of section 4.4
of the SmPC in order to add a new warning on
heart failure following a detailed cumulative
review of post-marketing data. The Package
Leaflet and Labelling are updated accordingly.
In addition, the MAH took the opportunity to
update the package leaflet to include
hypothyroidism as a common side effect.”

Methylthioninium chloride Proveblue -

methylthioninium chloride -
EMEA/H/C/002108/II/0052/G
Provepharm SAS, Rapporteur: Kristina Dunder,
“-Update of sections 4.2 and 5.2 of the SmPC in
order to change the posology recommendations
in patients with renal and hepatic impairment
and update the pharmacokinetic information
respectively, based on results from: an open-
label, parallel group, population-matched,
single-dose study to investigate the influence of
renal impairment on the pharmacokinetics of
ProvayBlue (Study Report PVP-2016006). The
package leaflet and labelling are updated
accordingly. The applicant takes this opportunity
to update the Product Information according to
the QRD template v10.1 and v10.2.
-Update of sections 4.5 and 5.2 of the SmPC in
order to add drug-drug interaction information
with other medicinal products and update the
pharmacokinetic information respectively, based
on results from: an open-label, randomized,
two-period, crossover study to assess the effect
of a single dose of methylene blue 5 mg/ml on
the pharmacokinetics of the probe drugs
midazolam, caffeine, warfarin, omeprazole and
dextromethorphan in healthy subjects (Study
Report PVP-2016004). The package leaflet and
labelling are updated accordingly.”

Obizur - susoctocog alfa -

EMEA/H/C/002792/II/0042
Baxalta Innovations GmbH, Rapporteur: Andrea

EMA/CHMP/625004/2021 Page 59/67

Laslop, “Submission of the final report from
OBIZUR study 241502. This is a Phase 3,
multicenter, single-arm, open-label study of the
efficacy and safety of B-Domain deleted
recombinant porcine factor VIII (BAX 802) in
subjects with congenital hemophilia A with
factor VIII inhibitors undergoing surgical or
other invasive procedures. No changes to the PI
are proposed.”

REKAMBYS - rilpivirine -
EMEA/H/C/005060/II/0008
Janssen-Cilag International N.V., Rapporteur:
Johann Lodewijk Hillege, “Update of sections 4.8
and 5.1 of the SmPC in order to update efficacy
and safety information based on week 96
results from the clinical study 207966 (ATLAS-
2M). This is an open-label, randomized, Phase
IIIb trial to demonstrate non-inferior antiviral
activity and safety of CAB + RPV Q8W compared
with CAB + RPV Q4W. Supporting Cabotegravir
(CAB) Long-acting Injectable (LA) + Rilpivirine
(RPV) LA every 2 months (Q8W) dosing regimen
for the treatment of HIV-1 infection.”

RETSEVMO - selpercatinib -
EMEA/H/C/005375/II/0010
Eli Lilly Nederland B.V., Rapporteur: Alexandre
Moreau, “Update of sections 4.2 and 5.3 of the
SmPC in order to reflect the need to monitor
open growth plates in adolescent patients based
on the results from a non-clinical juvenile
toxicity study LOXO-292-TOX-028. The Package
Leaflet is updated accordingly. In addition, the
MAH took the opportunity to correct figures in
section 5.1 of the SmPC.”

Revatio - sildenafil -
EMEA/H/C/000638/II/0098
Upjohn EESV, Rapporteur: Johann Lodewijk
Hillege, “Update of sections 4.8 and 5.1 to
include long-term safety data in adults for the
approved dose, and evidence of safe and
effective use in adults in higher than
recommended doses, based on study
A1481324; a multinational, multicentre
randomized, double-blind, parallel-group study
in 385 adults with Pulmonary Arterial
Hypertension (PAH) undertaken to assess the
effects of different dose levels of oral sildenafil
on mortality. In addition, the MAH took the
opportunity to implement editorial changes in

EMA/CHMP/625004/2021 Page 60/67

the SmPC.”

Rydapt - midostaurin -
EMEA/H/C/004095/II/0022, Orphan
Novartis Europharm Limited, Rapporteur: Paula
Boudewina van Hennik, “Update of section 5.1
of the SmPC in order to update efficacy
information in elderly patients, based on final
results from study ADE02T listed as PAES in the
Annex II; this is a phase II study to investigate
the efficacy of midostaurin in combination with
intensive induction, consolidation including
allogenic SCT and single agent maintenance in
patients aged 18-70 with FLT3 ITD mutated
AML .”

Vaxzevria - COVID 19 Vaccine (ChAdOx1 S

[recombinant]) -
EMEA/H/C/005675/II/0047
AstraZeneca AB, Rapporteur: Sol Ruiz,
“Submission of the final report from MS1222-
0004 study "Binding of PF4 to AZD1222 and
Purified ChAdOx1" and the Greinacher et al
(Greinacher et al 2021) paper, titled "A
prothrombotic thrombocytopenic disorder
resembling heparin-induced thrombocytopenia
following Coronavirus-19 vaccination" listed as a
category 3 study in the RMP.”

Veklury - remdesivir -
EMEA/H/C/005622/II/0028/G
Gilead Sciences Ireland UC, Rapporteur: Janet
Koenig, “
C.I.4. Grouping variation to update of section
5.1 of the SmPC in order to add information
related to in vitro testing reports of B.1.1.28
and B.1.617 variants with additional provision of
the cell culture resistance report to further
understand the antiviral activity of Remdesivir.
They are listed as part of the specific obligation
(SOB 012) in the Annex II of the renewal
procedure EMEA/H/C/005622/R/0015 for
Veklury.
C.I.13.Grouping variation for the submission of
the virology reports for GS-US-540-5773 and
GS-US-540-5774 studies and the submission of
the ACTT-1 final viral load analysis included as
part of the specific obligation (SOB 012) in the
Annex II of the renewal procedure
EMEA/H/C/005622/R/0015 for Veklury.”

Vocabria - cabotegravir -

EMA/CHMP/625004/2021 Page 61/67

EMEA/H/C/004976/II/0008
ViiV Healthcare B.V., Rapporteur: Jean-Michel
Race, “Update of sections 4.8 and 5.1 of the
SmPC in order to update efficacy and safety
information based on week 96 results from the
clinical study 207966 (ATLAS-2M). This is an
open-label, randomized, Phase IIIb trial to
demonstrate non-inferior antiviral activity and
safety of CAB + RPV Q8W compared with CAB +
RPV Q4W. Supporting Cabotegravir (CAB) Long-
acting Injectable (LA) + Rilpivirine (RPV) LA
every 2 months (Q8W) dosing regimen for the
treatment of HIV-1 infection.”

WS2163
Combivir-EMEA/H/C/000190/WS2163
/0103
Kivexa-EMEA/H/C/000581/WS2163/0093
Trizivir-EMEA/H/C/000338/WS2163/0127
ViiV Healthcare B.V., Lead Rapporteur: Jean-
Michel Race, “Update of section 5.2 of the SmPC
in order to add new information on the
elimination half-life of lamivudine, based on
final results from studies 204993 and 204994.
Study 204993 was a phase I, relative oral
bioavailability study of different fixed dose
combinations of dolutegravir and lamivudine in
healthy subjects. Study 204994 was an open-
label, randomized, single dose, crossover,
bioequivalence study of fixed-dose combination
tablet(s) of dolutegravir and lamivudine versus
dolutegravir and lamivudine single entities and
food effect assessment in healthy volunteers.
In addition, the MAH took the opportunity to
bring the PI in line with the latest QRD template
version 10.2 and to introduce minor editorial
changes.”

B.6.10. CHMP-PRAC assessed procedures

LUTATHERA - lutetium (177lu)

oxodotreotide -
EMEA/H/C/004123/II/0030, Orphan
Advanced Accelerator Applications, Rapporteur:
Janet Koenig, PRAC Rapporteur: Adam
Przybylkowski, “Update of the SmPC sections
4.4, 4.8 and 5.1 based on the pivotal Phase III
study, NETTER-1. Additionally, updates are
proposed in the PI to correct some information
based on currently approved data. The PL is
updated accordingly. The RMP v. 2.0 has been

EMA/CHMP/625004/2021 Page 62/67

submitted. The MAH took also the opportunity
to update the details of local representatives in
the PL.”

Mekinist - trametinib -
EMEA/H/C/002643/II/0051
Novartis Europharm Limited, Rapporteur: Paula
Boudewina van Hennik, PRAC Rapporteur: David
Olsen, “Update of section 4.2 and 5.2 of the
SmPC in order to change posology
recommendations in hepatic impairment and
update pharmacokinetic information based on
final results from study MEC116354 listed as a
category 3 study in the RMP; this is a Phase I
Trial of Single Agent Trametinib (GSK1120212)
in Advanced Cancer Patients with Hepatic
Dysfunction. The RMP version 18 has also been
submitted.”

Onpattro - patisiran -
EMEA/H/C/004699/II/0022, Orphan
Alnylam Netherlands B.V., Rapporteur: Kristina
Dunder, PRAC Rapporteur: Rhea Fitzgerald,
“Type II variation C.I.4 in the Summary of
Product Characteristics (SmPC), Labelling or
Package Leaflet (PL) due to new quality,
preclinical, clinical or pharmacovigilance data:
update of sections 4.2, 4.8, 5.1 and 5.2 of the
SmPC to confirm that the safety profile of
pasitiran in liver transplant recipients is
comparable to data in patients without liver
transplant, based on final results from study
ALN-TTR02-008, a global phase 3b, open-label,
extension study to evaluate safety, efficacy and
pharmacokinetics of patisiran in patients with
hereditary transthyretin-mediated amyloidosis
(HATTR amyloidosis) with disease progression
post-orthotopic liver transplant (OLT). The RMP
version 1.1 has also been submitted. In
addition, the MAH took the opportunity to make
some minor changes to the English PI in SmPC
sections 5.1, 6.3 (In line with EMA
recommendation from procedure
EMEA/H/C/004699/IB/0014), PL sections 2
(minor typographical error changes), 6 (update
to contact numbers of local MAH representatives
in Cyprus and Malta, and MAH local
representative from ‘United Kingdom’ to ‘United
Kingdom [Northern Ireland] in line with the QRD
template version 10.2) and implement minor
linguistic changes and typographical error

EMA/CHMP/625004/2021 Page 63/67

corrections in the Italian PI translation.”

B.6.11. PRAC assessed procedures

PRAC Led
COMIRNATY - tozinameran -
EMEA/H/C/005735/II/0080
BioNTech Manufacturing GmbH, Rapporteur:
Filip Josephson, PRAC Rapporteur: Menno van
der Elst, PRAC-CHMP liaison: Johann Lodewijk
Hillege, “Update of section 4.4 of the SmPC in
order to amend an existing warning on anxiety-
related reactions to add “numbness” based on
the outcome of the Post-Authorisation Measure
PAM MEA-002.8 (EMEA/H/C/005735/MEA/002.8,
dated 30. September 2021).
In addition, the MAH took the opportunity to
make minor editorial changes throughout the
product information.”

B.6.12. CHMP-CAT assessed procedures

Abecma - idecabtagene vicleucel -

EMEA/H/C/004662/II/0005/G, Orphan,
ATMP
Celgene Europe B.V., Rapporteur: Rune Kjeken,
CHMP Coordinator: Ingrid Wang

Zolgensma - onasemnogene abeparvovec -

EMEA/H/C/004750/II/0020/G, Orphan,
ATMP
Novartis Gene Therapies EU Limited,
Rapporteur: Carla Herberts, CHMP Coordinator:
Johann Lodewijk Hillege

WS2181
Tecartus-EMEA/H/C/005102/WS2181/
0014
Yescarta-EMEA/H/C/004480/WS2181/
0044
Kite Pharma EU B.V., Lead Rapporteur: Jan
Mueller-Berghaus, CHMP Coordinator: Jan
Mueller-Berghaus

B.6.13. CHMP-PRAC-CAT assessed procedures

Skysona - elivaldogene autotemcel -

EMEA/H/C/003690/II/0002, Orphan,
ATMP
bluebird bio (Netherlands) B.V, Rapporteur:
Lisbeth Barkholt, CHMP Coordinator: Kristina

EMA/CHMP/625004/2021 Page 64/67

Dunder, PRAC Rapporteur: Brigitte Keller-
Stanislawski, “Submission of the final CSR for
study ALD-102. Risk Management Plan version
2.0 is updated accordingly.”

B.6.14. PRAC assessed ATMP procedures

B.6.15. Unclassified procedures and worksharing procedures of type I variations

WS2169
Mirapexin-
EMEA/H/C/000134/WS2169/0101
Sifrol-EMEA/H/C/000133/WS2169/0092
Boehringer Ingelheim International GmbH, Lead
Rapporteur: Sinan B. Sarac, “To update the
annexes to bring them in line with QRD version
10.1. In addition, a thorough review of the
annexes has been performed and
inconsistencies have been corrected.”

EMA/CHMP/625004/2021 Page 65/67

B.7. DOCUMENTS TABLED IN MMD AFTER THE CHMP PLENARY

B.7.1. Yearly Line listing for Type I and II variations

B.7.2. Monthly Line listing for Type I variations

B.7.3. Opinion on Marketing Authorisation transfer (MMD only)

B.7.4. Notifications in accordance with Article 61(3) of Council Directive 2001/83/EC

(MMD only)

B.7.5. Request for supplementary information relating to Notification of Type I variation

(MMD only)

B.7.6. Notifications of Type I Variations (MMD only)

C. Annex C - Post-Authorisation Measures (PAMs), (Line listing of Post authorisation

measures with a description of the PAM. Procedures starting in that given month with
assessment timetabled)

D. Annex D - Post-Authorisation Measures (PAMs), (Details on PAMs including description

and conclusion, for adoption by CHMP in that given month, or finalised ones with PRAC
recommendation and no adoption by CHMP needed)

E. Annex E - EMA CERTIFICATION OF PLASMA MASTER FILES

Information related to plasma master files cannot be released at the present time as these contain
commercially confidential information.

E.1. Timetables – starting & ongoing procedures: For information

PMF timetables starting and ongoing procedures Tabled in MMD and sent by post mail (folder E).

F. ANNEX F - Decision of the Granting of a Fee Reduction/Fee Waiver

G. ANNEX G

G.1. Final Scientific Advice (Reports and Scientific Advice letters):

Information related to Scientific Advice cannot be released at the present time as these contain
commercially confidential information.

EMA/CHMP/625004/2021 Page 66/67

G.1.1. List of procedures concluding at 08-11 November 2021 CHMP plenary:

G.1.2. List of procedures starting in November 2021 for December 2021 CHMP adoption of
outcomes

H. ANNEX H - Product Shared Mailboxes – e-mail address

EMA/CHMP/625004/2021 Page 67/67