EMA CHMP Meeting Minutes July 2025

Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands An agency of the European Union 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 © European Medicines Agency, 2025. Reproduction is authorised provided the source is acknowledged. 24 July 2025 EMA/CHMP/319030/2025 Corr.1 Minutes for the meeting on 21-24 July 2025 Chair: Bruno Sepodes – Vice-Chair: Outi Mäki-Ikola Health and safety information In accordance with the Agency’s health and safety policy, delegates are to be briefed on health, safety and emergency information and procedures prior to the start of the meeting. Disclaimers Some of the information contained in this set of minutes 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, these minutes 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 minutescannot 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). Correction in section 16.

Page 2/67 Table of contents 1. Introduction 9 1.1. Welcome and declarations of interest of members, alternates and experts ............ 9 1.2. Adoption of agenda ................................................................................................ 9 1.3. Adoption of the minutes ......................................................................................... 9 2. Oral Explanations 10 2.1. Pre-authorisation procedure oral explanations ..................................................... 10 2.1.1. Pridopidine - Orphan - EMEA/H/C/006261 ................................................................... 10 2.2. Re-examination procedure oral explanations ....................................................... 10 2.2.1. Kisunla - Donanemab - EMEA/H/C/006024 ................................................................. 10 2.2.2. Aplidin - plitidepsin - Orphan - EMEA/H/C/004354 ....................................................... 10 2.3. Post-authorisation procedure oral explanations ................................................... 11 2.4. Referral procedure oral explanations ................................................................... 11 3. Initial applications 11 3.1. Initial applications; Opinions ................................................................................ 11 3.1.1. Aqneursa - L-Acetylleucine - Orphan - EMEA/H/C/006327 ............................................. 11 3.1.2. BILDYOS - Denosumab - EMEA/H/C/006434 ............................................................... 11 3.1.3. BILPREVDA - Denosumab - EMEA/H/C/006435 ............................................................ 12 3.1.4. Ekterly - Sebetralstat - Orphan - EMEA/H/C/006211 .................................................... 12 3.1.5. Elevidys - Delandistrogene moxeparvovec - Orphan - ATMP - EMEA/H/C/005293 ............. 13 3.1.6. Eyluxvi - Aflibercept - EMEA/H/C/006282 ................................................................... 13 3.1.7. JELRIX - Autologous cartilage-derived articular chondrocytes, in-vitro expanded - ATMP - EMEA/H/C/004594 ................................................................................................... 13 3.1.8. Yeytuo - Lenacapavir - EMEA/H/C/006658 .................................................................. 14 3.1.9. Lenacapavir Gilead - Lenacapavir - Article 58 - EMEA/H/W/006659 ................................ 14 3.1.10. Macitentan Accord - Macitentan - EMEA/H/C/006524 ................................................... 15 3.1.11. Macitentan AccordPharma - Macitentan - EMEA/H/C/006523 ......................................... 15 3.1.12. Nurzigma - Pridopidine - Orphan - EMEA/H/C/006261 .................................................. 16 3.1.13. ROMVIMZA - Vimseltinib - Orphan - EMEA/H/C/006363 ................................................ 16 3.1.14. Tryngolza - Olezarsen - Orphan - EMEA/H/C/006477 ................................................... 16 3.1.15. Usrenty - Ustekinumab - EMEA/H/C/006794 ............................................................... 17 3.1.16. Voranigo - Vorasidenib - Orphan - EMEA/H/C/006284 .................................................. 17 3.1.17. Zurzuvae - Zuranolone - EMEA/H/C/006488 ............................................................... 18 3.2. Initial applications; List of outstanding issues (Day 180; Day 120 for procedures with accelerated assessment timetable) ...................................................................... 18 3.2.1. Clesrovimab - EMEA/H/C/006497 .............................................................................. 18 3.2.2. Denosumab - EMEA/H/C/006239 ............................................................................... 19

Page 3/67 3.2.3. Enzalutamide - EMEA/H/C/006612 ............................................................................. 19 3.2.4. Insulin icodec / Semaglutide - EMEA/H/C/006279 ........................................................ 19 3.2.5. Elinzanetant - EMEA/H/C/006298 .............................................................................. 19 3.2.6. ACELLULAR PERTUSSIS VACCINE - EMEA/H/C/006304 ................................................. 20 3.2.7. Rivaroxaban - EMEA/H/C/006643 .............................................................................. 20 3.2.8. Teduglutide - EMEA/H/C/006564 ............................................................................... 20 3.2.9. Rilzabrutinib - Orphan - EMEA/H/C/006425 ................................................................. 21 3.3. Initial applications; List of questions (Day 120; Day 90 for procedures with accelerated assessment timetable) ...................................................................... 21 3.3.1. Copper (64Cu) oxodotreotide - Orphan - EMEA/H/C/006608 ......................................... 21 3.3.2. Liraglutide - EMEA/H/C/006620 ................................................................................. 21 3.3.3. Furosemide - PUMA - EMEA/H/C/006617 .................................................................... 21 3.3.4. Brensocatib - PRIME - EMEA/H/C/005820 ................................................................... 22 3.3.5. Apitegromab - PRIME - Orphan - EMEA/H/C/005909 .................................................... 22 3.3.6. Semaglutide - EMEA/H/C/006426 .............................................................................. 22 3.3.7. Liraglutide - EMEA/H/C/006615 ................................................................................. 22 3.3.8. Tovorafenib - Orphan - EMEA/H/C/006140 .................................................................. 23 3.3.9. Paltusotine - Orphan - EMEA/H/C/006636 ................................................................... 23 3.3.10. Pertuzumab - EMEA/H/C/006583 ............................................................................... 23 3.3.11. Remibrutinib - EMEA/H/C/006313 .............................................................................. 23 3.3.12. INFLUENZA VACCINE - EMEA/H/C/006674 .................................................................. 24 3.3.13. Autologous melanoma-derived tumour infiltrating lymphocytes, ex vivo-expanded - ATMP - EMEA/H/C/006563 ................................................................................................... 24 3.3.14. Tocilizumab - EMEA/H/C/006416 ............................................................................... 24 3.4. Update on on-going initial applications for Centralised procedure ........................ 25 3.4.1. Belumosudil - Orphan - EMEA/H/C/006421 ................................................................. 25 3.4.2. Golimumab - EMEA/H/C/006621 ................................................................................ 25 3.4.3. Mavorixafor - Orphan - EMEA/H/C/006496 .................................................................. 25 3.4.4. Plozasiran - Orphan - EMEA/H/C/006579 .................................................................... 25 3.5. Re-examination of initial application procedures under Article 9(2) of Regulation no 726/2004 ............................................................................................................. 26 3.5.1. Atropine sulfate FGK - Atropine - PUMA - EMEA/H/C/006385 ......................................... 26 3.5.2. Austedo - Deutetrabenazine - EMEA/H/C/006371 ........................................................ 26 3.5.3. Kisunla - Donanemab - EMEA/H/C/006024 ................................................................. 26 3.6. Initial applications in the decision-making phase ................................................. 27 3.7. Withdrawals of initial marketing authorisation application .................................. 27 3.7.1. Lifileucel - ATMP - EMEA/H/C/004741 ......................................................................... 27 3.7.2. Aplidin - plitidepsin - Orphan - EMEA/H/C/004354 ....................................................... 27 3.7.3. Bifikafusp alfa / Onfekafusp alfa - EMEA/H/C/005651 ................................................... 28 3.7.4. Eflornithine – EMEA/H/C/006067 ............................................................................... 28

Page 4/67 4. Extension of marketing authorisation according to Annex I of Commission Regulation (EC) No 1234/2008 28 4.1. Extension of marketing authorisation according to Annex I of Commission Regulation (EC) No 1234/2008; Opinion ................................................................................ 28 4.1.1. Azacitidine Accord - Azacitidine - EMEA/H/C/005147/X/0021 ........................................ 28 4.2. Extension of marketing authorisation according to Annex I of Commission Regulation (EC) No 1234/2008; Day 180 list of outstanding issues ....................................... 29 4.2.1. Enzalutamide Viatris - Enzalutamide - EMEA/H/C/006299/X/0003 ................................. 29 4.2.2. Hetlioz - Tasimelteon - Orphan - EMEA/H/C/003870/X/0039 ......................................... 29 4.2.3. Livmarli - Maralixibat - Orphan - EMEA/H/C/005857/X/0015 ......................................... 29 4.2.4. Pyrukynd - Mitapivat - Orphan - EMEA/H/C/005540/X/0010/G ...................................... 30 4.2.5. Remsima - Infliximab - EMEA/H/C/002576/X/0149 ...................................................... 30 4.3. Extension of marketing authorisation according to Annex I of Commission Regulation (EC) No 1234/2008; Day 120 List of question ...................................................... 31 4.3.1. Abrysvo - Respiratory syncytial virus vaccine (bivalent, recombinant) - EMA/X/000025805131 4.3.2. Akynzeo - Fosnetupitant / Netupitant / Palonosetron - EMA/X/0000258060 .................... 31 4.3.3. Camcevi – Leuprorelin - EMA/X/0000258054 .............................................................. 31 4.3.4. Jorveza – Budesonide - EMA/X/0000257468 ............................................................... 32 4.3.5. Lojuxta – Lomitapide - EMA/X/0000258068 ................................................................ 32 4.3.6. Nexviadyme - Avalglucosidase alfa - EMA/X/0000258013 ............................................. 32 4.3.7. Olumiant – Baricitinib - EMA/X/0000257923 ............................................................... 33 4.3.8. Scemblix – Asciminib - EMA/X/0000256688 ................................................................ 33 4.4. Update on on-going extension application according to Annex I of Commission Regulation (EC) No 1234/2008 ............................................................................ 33 4.5. Re-examination procedure of extension of marketing authorisation according to Annex I of Commission Regulation (EC) No 1234/2008 ....................................... 33 5. Type II variations - variation of therapeutic indication procedure according to Annex I of Commission Regulation (EC) No 1234/20085.1. Type II variations - variation of therapeutic indication procedure according to Commission Regulation (EC) No 1234/2008; Opinions or Requests for supplementary information ........................................................................................................... 34 5.1.1. Alhemo – Concizumab - EMA/VR/0000244862 ............................................................. 34 5.1.2. BAQSIMI – Glucagon - EMA/VR/0000244909 .............................................................. 34 5.1.3. BESPONSA - Inotuzumab ozogamicin - EMA/VR/0000257310 ........................................ 35 5.1.4. Breyanzi - Lisocabtagene maraleucel – ATMP – EMA/VR/0000265024............................. 35 5.1.5. Cejemly – Sugemalimab - EMA/VR/0000261157 .......................................................... 36 5.1.6. Clopidogrel Zentiva - Clopidogrel - EMEA/H/C/000975/II/0092 ...................................... 36 5.1.7. CRYSVITA – Burosumab - EMA/VR/0000263400 .......................................................... 37 5.1.8. Elucirem/ Vueway – Gadopiclenol - EMA/VR/0000249008 ............................................. 37 5.1.9. Eylea – Aflibercept - EMA/VR/0000264981 .................................................................. 37

Page 5/67 5.1.10. Gazyvaro – Obinutuzumab - EMA/VR/0000244907....................................................... 38 5.1.11. Iclusig – Ponatinib - EMA/VR/0000263550 .................................................................. 38 5.1.12. Invokana - Canagliflozin - EMEA/H/C/002649/II/0069 .................................................. 39 5.1.13. Keytruda – Pembrolizumab - EMA/VR/0000245108 ...................................................... 39 5.1.14. LIBTAYO – Cemiplimab - EMA/VR/0000264999 ........................................................... 40 5.1.15. mRESVIA - Respiratory syncytial virus mRNA vaccine (nucleoside modified) - EMA/VR/0000248175 ............................................................................................... 40 5.1.16. Neuraceq - Florbetaben (18F) - EMA/VR/0000227744 .................................................. 40 5.1.17. Noxafil – Posaconazole - EMA/VR/0000263360 ............................................................ 41 5.1.18. Recarbrio - Imipenem / Cilastatin / Relebactam - EMA/VR/0000265089 ......................... 41 5.1.19. Scemblix – Asciminib - EMA/VR/0000265010 .............................................................. 42 5.1.20. SIRTURO – Bedaquiline - EMA/VR/0000249065 ........................................................... 42 5.1.21. Sogroya – Somapacitan - EMA/VR/0000264734 .......................................................... 43 5.1.22. Taltz - Ixekizumab - EMEA/H/C/003943/II/0053.......................................................... 43 5.1.23. Tevimbra - Tislelizumab - EMEA/H/C/005919/II/0018 .................................................. 44 5.1.24. TEZSPIRE – Tezepelumab - EMA/VR/0000245013 ........................................................ 44 5.1.25. VEYVONDI - Vonicog alfa - EMA/VR/0000264863 ......................................................... 45 5.1.26. Xerava – Eravacycline - EMA/VR/0000265697 ............................................................. 45 5.2. Update on on-going Type II variation; variation of therapeutic indication procedure according to Commission Regulation (EC) No 1234/2008 .................................... 46 5.3. Re-examination of Type II variation; variation of therapeutic indication procedure according to Commission Regulation (EC) No 1234/2008 .................................... 46 6. Medical devices 46 6.1. Ancillary medicinal substances - initial consultation ............................................ 46 6.2. Ancillary medicinal substances – post-consultation update .................................. 46 6.3. Companion diagnostics - initial consultation ........................................................ 46 6.3.1. In vitro diagnostic medical device - EMEA/H/D/006768 ................................................ 46 6.3.2. VENTANA HER2 Dual ISH DNA Probe Cocktail RxDx - In vitro diagnostic medical device - EMEA/H/D/006723 ................................................................................................... 47 6.3.3. VENTANA HER2 (4B5) Rabbit Monoclonal Primary Antibody RxDx - In vitro diagnostic medical device - EMEA/H/D/006724 ...................................................................................... 47 6.4. Companion diagnostics – follow-up consultation .................................................. 47 7. Procedure under Article 83(1) of Regulation (EC) 726/2004 (Compassionate Use) 47 7.1. Procedure under Article 83(1) of Regulation (EC) 726/2004 (Compassionate Use)47 8. Pre-submission issues 48 8.1. Pre-submission issue ............................................................................................ 48 8.1.1. Acoziborole - Article 58 – H0006686 .......................................................................... 48 8.2. Priority Medicines (PRIME) ................................................................................... 48

Page 6/67 9. Post-authorisation issues 48 9.1. Post-authorisation issues ..................................................................................... 48 9.1.1. Amvuttra - Vutrisiran - Orphan - EMEA/H/C/005852/II/0015 ........................................ 48 9.1.2. Tecovirimat SIGA – Tecovirimat - EMA/S/0000248804 ................................................. 48 9.1.3. WS2780 Riltrava Aerosphere-EMEA/H/C/005311/WS2780/0017 Trixeo Aerosphere- EMEA/H/C/004983/WS2780/0024 ............................................................................. 49 9.1.4. Fluenz Tetra - Influenza vaccine (live attenuated, nasal) – EMEA/H/C/002617 ................ 49 9.1.5. Volibris – Ambrisentan - EMA/VR/0000266441 ............................................................ 49 9.1.6. COMIRNATY - COVID-19 mRNA vaccine - EMA/VR/0000275515 .................................... 50 9.1.7. BIMERVAX - COVID-19 vaccine (recombinant, adjuvanted) - EMA/VR/0000279224 .......... 50 9.1.8. Spikevax - COVID-19 mRNA vaccine - EMA/VR/0000278795 ......................................... 50 9.1.9. Holoclar - ex vivo expanded autologous human corneal epithelial cells containing stem cells – ATMP - EMEA/H/C/002450/R/0058 ............................................................................ 51 9.1.10. Evrysdi – Risdiplam – EMEA/H/C/005145 .................................................................... 51 9.1.11. Inrebic - Fedratinib - EMEA/H/C/005026/II/0027, Orphan ............................................ 51 10. Referral procedures 51 10.1. Procedure for Centrally Authorised products under Article 20 of Regulation (EC) No 726/2004 ............................................................................................................. 51 10.1.1. Oxbryta - Voxelotor - EMEA/H/A-20/1538/C/004869/0014 ........................................... 51 10.1.2. IXCHIQ - Chikungunya vaccine (live) - EMA/REF/0000269473 ....................................... 52 10.1.3. Tecovirimat SIGA – Tecovirimat - EMA/REF/0000287477 .............................................. 52 10.2. Requests for CHMP Opinion under Article 5(3) of Regulation (EC) No 726/2004 . 53 10.2.1. Colistimethate sodium (CMS) – EMEA/H/A-5(3)/1524 .................................................. 53 10.3. Procedure under Articles 5(2) and 10 of Regulation (EC) No 726/2004 ............... 53 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 ......................................................................................................... 53 10.5. Harmonisation - Referral procedure under Article 30 of Directive 2001/83/EC .... 53 10.6. Community Interests - Referral under Article 31 of Directive 2001/83/EC .......... 53 10.7. Re-examination Procedure under Article 32(4) of Directive 2001/83/EC ............. 53 10.8. Procedure under Article 107(2) of Directive 2001/83/EC .................................... 53 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 ............................................................................................................................. 54 10.10. Procedure under Article 29 of Regulation (EC) 1901/2006................................... 54 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 ................................................................ 54 11. Pharmacovigilance issue 54 11.1. Early Notification System ..................................................................................... 54

Page 7/67 12. Inspections 54 12.1. GMP inspections ................................................................................................... 54 12.2. GCP inspections .................................................................................................... 54 12.3. Pharmacovigilance inspections ............................................................................. 54 12.4. GLP inspections .................................................................................................... 54 13. Innovation Task Force 55 13.1. Minutes of Innovation Task Force ......................................................................... 55 13.2. Innovation Task Force briefing meetings .............................................................. 55 13.3. Requests for CHMP Opinion under Article 57(1)J and (1)P of Regulation (EC) No 726/2004 ............................................................................................................. 55 13.4. Nanomedicines activities ...................................................................................... 55 14. Organisational, regulatory and methodological matters 55 14.1. Mandate and organisation of the CHMP ................................................................ 55 14.1.1. Vote by Proxy ......................................................................................................... 55 14.1.2. CHMP membership ................................................................................................... 55 14.2. Coordination with EMA Scientific Committees....................................................... 55 14.2.1. Pharmacovigilance Risk Assessment Committee (PRAC) ............................................... 55 14.2.2. Paediatric Committee (PDCO) .................................................................................... 56 14.3. Coordination with EMA Working Parties/Working Groups/Drafting Groups ......... 56 14.3.1. Biologics Working Party (BWP) .................................................................................. 56 14.3.2. Scientific Advice Working Party (SAWP) ...................................................................... 56 14.3.3. The CHMP noted the update.Election of Oncology Working Party Vice-Chair .................... 56 14.3.4. Election of 3Rs Working Party Chair and Vice-Chair ...................................................... 57 14.3.5. Election of CNSWP Vice-chair .................................................................................... 57 14.3.6. Election of VWP Vice-chair ........................................................................................ 57 14.3.7. CVSWP Response to the CHMP request on indication wording ........................................ 57 14.3.8. Nomination of CHMP representatives to the PCWP and HCPWP ...................................... 57 14.3.9. ICH Q3E draft Guideline on Extractables and Leachables - Step 2b ................................ 57 14.4. Cooperation within the EU regulatory network ..................................................... 58 14.5. Cooperation with International Regulators........................................................... 58 14.6. Contacts of the CHMP with external parties and interaction with the Interested Parties to the Committee ...................................................................................... 58 14.7. CHMP work plan ................................................................................................... 58 14.8. Planning and reporting ......................................................................................... 58 14.9. Others .................................................................................................................. 58 15. Any other business 58 15.1. AOB topic .............................................................................................................. 58

Page 8/67 15.1.1. GIREX rules ............................................................................................................ 58 16. List of participants 59 Explanatory notes 65

Page 9/67 1. Introduction 1.1. Welcome and declarations of interest of members, alternates and experts The Chairperson opened the meeting by welcoming all participants. The meeting was held in person. In accordance with the Agency’s policy on handling of declarations of interests of scientific Committees’ members and experts, based on the declarations of interest submitted by the Committee members, alternates and experts and based on the topics in the agenda of the meeting, the Committee Secretariat announced the restricted involvement of some Committee members, alternates and experts for concerned agenda topics. Participants were asked to declare any changes, omissions or errors to their declared interests and/or additional restrictions concerning the matters for discussion. No new or additional interests or restrictions were declared. Restrictions applicable to this meeting are captured in the list of participants included in the minutes. Discussions, deliberations and voting took place in full respect of the restricted involvement of Committee members and experts in line with the relevant provisions of the Rules of Procedure. All decisions, recommendations and advice were agreed by consensus, unless otherwise specified. 1.2. Adoption of agenda CHMP agenda for 21-24 July 2025. The CHMP adopted the agenda. 1.3. Adoption of the minutes CHMP minutes for the 22-25 April 2025 and the 19-22 May 2025 meetings. The CHMP adopted the minutes for the 22-25 April 2025 and the 19-22 May 2025 plenary meetings. Minutes from PReparatory and Organisational Matters (PROM) meeting held on 14 July 2025. The CHMP adopted the minutes from the PROM meeting held on 14 July 2025.

Page 10/67 2. Oral Explanations 2.1. Pre-authorisation procedure oral explanations 2.1.1. Pridopidine - Orphan - EMEA/H/C/006261 Prilenia Therapeutics B.V.; treatment of Huntington's disease Scope: Oral explanation Action: Oral explanation to be held on 22 July 2025 at 11:00 Patient representatives An oral explanation was held on 22 July 2025. The presentation by the applicant focused on 3.1 2.2. Re-examination procedure oral explanations 2.2.1. Kisunla - Donanemab - EMEA/H/C/006024 Eli Lilly Nederland B.V.; to slow disease progression in adult patients with Alzheimer’s disease (AD). Scope: Oral explanation Action: Oral explanation to be held on 21 July 2025 at 14:00 Opinion adopted on 27.03.2025. List of Outstanding Issues adopted on 12.12.2024, 25.04.2024. List of Questions adopted on 14.12.2023. An oral explanation was held on 21 July 2025. The presentation by the applicant focused on See 3.5 2.2.2. Aplidin - plitidepsin - Orphan - EMEA/H/C/004354 Pharma Mar, S.A.; treatment of multiple myeloma Scope: Oral explanation Action: Oral explanation to be held on 23 July 2025 at 11:00 An oral explanation was held on 23 July 2025. The presentation by the applicant focused on

Page 11/67 See 3.7 2.3. Post-authorisation procedure oral explanations No items 2.4. Referral procedure oral explanations No items 3. Initial applications 3.1. Initial applications; Opinions 3.1.1. Aqneursa - L-Acetylleucine - Orphan - EMEA/H/C/006327 Intrabio Ireland Limited; chronic treatment of Niemann-Pick Type C (NPC) in adults and children from birth List of Outstanding Issues adopted on 25.04.2025, 27.02.2025. List of Questions adopted on 17.10.2024. The CHMP noted the letter of recommendation dated 23 July 2025. 3.1.2. BILDYOS - Denosumab - EMEA/H/C/006434 Henlius Europe GmbH; treatment of osteoporosis and bone loss

Page 12/67 List of Outstanding Issues adopted on 27.02.2025. List of Questions adopted on 19.09.2024. 3.1.3. BILPREVDA - Denosumab - EMEA/H/C/006435 Henlius Europe GmbH; prevention of skeletal related events in adults with advanced malignancies involving bone List of Outstanding Issues adopted on 27.02.2025. List of Questions adopted on 19.09.2024. 3.1.4. Ekterly - Sebetralstat - Orphan - EMEA/H/C/006211 Kalvista Pharmaceuticals (Ireland) Limited; treatment of hereditary angioedema (HAE) attacks in adult and adolescents aged 12 years and older

Page 13/67 Furthermore, the CHMP considered that sebetralstat is a new active substance, as claimed 3.1.5. Elevidys - Delandistrogene moxeparvovec - Orphan - ATMP - EMEA/H/C/005293 Roche Registration GmbH; treatment of ambulatory patients aged 3 to 7 years old with Duchenne muscular dystrophy List of Outstanding Issues adopted on 16.04.2025. List of Questions adopted on 11.10.2024. Based on the draft opinion prepared by the CAT, the Committee adopted a negative opinion by consensus recommending the refusal of the granting of the marketing authorisation. The CHMP assessment report was adopted. The refusal question-and-answer document was circulated for information. 3.1.6. Eyluxvi - Aflibercept - EMEA/H/C/006282 biolitec pharma Limited Zweigniederlassung Jena; treatment of age-related macular degeneration (AMD) and visual impairment 14.11.2024. 3.1.7. JELRIX - Autologous cartilage-derived articular chondrocytes, in-vitro expanded - ATMP - EMEA/H/C/004594 TETEC Tissue Engineering Technologies AG; repair of symptomatic, localised, full-thickness

Page 14/67 cartilage defects of the knee joint grade III or IV List of Outstanding Issues adopted on 13.06.2025, 21.03.2025. List of Questions adopted on 19.04.2024. Based on the draft opinion prepared by the CAT, the Committee adopted a negative opinion by majority recommending the refusal of the granting of the marketing authorisation. The CHMP assessment report was adopted. The divergent position was appended to the opinion. The refusal question-and-answer document was circulated for information. The CHMP noted the re-examination request by the applicant. 3.1.8. Yeytuo - Lenacapavir - EMEA/H/C/006658 Gilead Sciences Ireland Unlimited Company; pre-exposure prophylaxis to prevent HIV-1 Known active substance (Article 8(3) of Directive No 2001/83/EC) List of Questions adopted on 20.05.2025. 3.1.9. Lenacapavir Gilead - Lenacapavir - Article 58 - EMEA/H/W/006659 Gilead Sciences Ireland Unlimited Company; pre-exposure prophylaxis to prevent HIV-1 Known active substance (Article 8(3) of Directive No 2001/83/EC)

Page 15/67 The Committee adopted the scientific opinion for lenacapavir in accordance with Article 58 of Regulation (EC) No. 726/2004. 3.1.10. Macitentan Accord - Macitentan - EMEA/H/C/006524 Accord Healthcare; treatment of pulmonary arterial hypertension (PAH) Generic application (Article 10(1) of Directive No 2001/83/EC), Generic of Opsumit 19.09.2024. 3.1.11. Macitentan AccordPharma - Macitentan - EMEA/H/C/006523 Accord Healthcare; treatment of pulmonary arterial hypertension (PAH) Generic application (Article 10(1) of Directive No 2001/83/EC), Generic of Opsumit 19.09.2024.

Page 16/67 3.1.12. Nurzigma - Pridopidine - Orphan - EMEA/H/C/006261 Prilenia Therapeutics B.V.; treatment of Huntington's disease Patient representatives The Committee adopted a negative opinion by consensus recommending the refusal of the granting of the conditional marketing authorisation. The CHMP assessment report was adopted. The question-and-answer document was circulated for information. See 2.1 3.1.13. ROMVIMZA - Vimseltinib - Orphan - EMEA/H/C/006363 Deciphera Pharmaceuticals (Netherlands) B.V.; Treatment of adult patients with tenosynovial giant cell tumour (TGCT) who are not amenable to surgery 14.11.2024. Furthermore, the CHMP considered that Vimseltinib is a new active substance, as claimed 3.1.14. Tryngolza - Olezarsen - Orphan - EMEA/H/C/006477 Ionis Ireland Limited; treatment of familial chylomicronemia syndrome

Page 17/67 Furthermore, the CHMP considered that Olezarsen is a new active substance, as claimed by the applicant. The CHMP noted the letter of recommendation dated 23 July 2025. The CHMP adopted the similarity assessment report. 3.1.15. Usrenty - Ustekinumab - EMEA/H/C/006794 Biosimilar Collaborations Ireland Limited; treatment of Crohn’s Disease, treatment of Plaque psoriasis, Psoriatic arthritis (PsA) 3.1.16. Voranigo - Vorasidenib - Orphan - EMEA/H/C/006284 Les Laboratoires Servier; treatment of predominantly non-enhancing astrocytoma or oligodendroglioma List of Outstanding Issues adopted on 30.01.2025, 19.09.2024, 25.07.2024. List of Questions adopted on 23.04.2024.

Page 18/67 Furthermore, the CHMP considered that Vorasidenib is a new active substance, as claimed The CHMP noted the letter of recommendation dated 21 July 2025. The CHMP adopted the similarity assessment report. 3.1.17. Zurzuvae - Zuranolone - EMEA/H/C/006488 Biogen Netherlands B.V.; treatment of postpartum depression (PPD) in adults Furthermore, the CHMP considered that Zuranolone is a new active substance, as claimed The CHMP noted the letter of recommendation dated 18 July 2025. 3.2. Initial applications; List of outstanding issues (Day 180; Day 120 for procedures with accelerated assessment timetable) 3.2.1. Clesrovimab - EMEA/H/C/006497 prevention of infections with respiratory syncytial virus (RSV) and lower respiratory tract disease (LRTD)

Page 19/67 issues. 3.2.2. Denosumab - EMEA/H/C/006239 prevention of skeletal related events in adults with advanced malignancies involving bone issues. 3.2.3. Enzalutamide - EMEA/H/C/006612 treatment of prostate cancer issues. 3.2.4. Insulin icodec / Semaglutide - EMEA/H/C/006279 treatment of adults with type 2 diabetes mellitus insufficiently controlled on basal insulin or glucagon-like peptide 1 (GLP-1) receptor agonists Scope: List of outstanding issues; Request by the applicant for an extension to the clock- stop to respond to the list of questions adopted in February 2025. issues. respond to the list of questions adopted in February 2025. 3.2.5. Elinzanetant - EMEA/H/C/006298 for the treatment of moderate to severe vasomotor symptoms (VMS)

Page 20/67 issues. 3.2.6. ACELLULAR PERTUSSIS VACCINE - EMEA/H/C/006304 indicated as active booster immunization against pertussis of persons aged 11 years onwards and passive protection against pertussis in early infancy following maternal immunization during pregnancy List of Questions adopted on 14.11.2024. issues. 3.2.7. Rivaroxaban - EMEA/H/C/006643 prevention of atherothrombotic events Scope: List of outstanding issues; Request by the applicant for an extension to the clock- stop to respond to the list of questions adopted in February 2025. issues. respond to the list of questions adopted in February 2025. 3.2.8. Teduglutide - EMEA/H/C/006564 treatment of Short Bowel Syndrome issues.

Page 21/67 3.2.9. Rilzabrutinib - Orphan - EMEA/H/C/006425 Sanofi B.V.; for the treatment of persistent or chronic immune thrombocytopenia (ITP) issues. 3.3. Initial applications; List of questions (Day 120; Day 90 for procedures with accelerated assessment timetable) 3.3.1. Copper (64Cu) oxodotreotide - Orphan - EMEA/H/C/006608 Cis Bio International; positron emission tomography (PET) for localization of somatostatin receptor positive neuroendocrine neoplasms (NENs). 3.3.2. Liraglutide - EMEA/H/C/006620 treatment of diabetes and weight management 3.3.3. Furosemide - PUMA - EMEA/H/C/006617 treatment of all conditions requiring diuresis due to mechanical obstruction or venous insufficiency.

Page 22/67 3.3.4. Brensocatib - PRIME - EMEA/H/C/005820 treatment of non-cystic fibrosis bronchiectasis 3.3.5. Apitegromab - PRIME - Orphan - EMEA/H/C/005909 Scholar Rock Netherlands B.V.; treatment of 5q spinal muscular atrophy (SMA) the list of questions 3.3.6. Semaglutide - EMEA/H/C/006426 treatment of non-cirrhotic metabolic dysfunction-associated steatohepatitis with liver fibrosis 3.3.7. Liraglutide - EMEA/H/C/006615 treatment of adults, adolescents and children aged 10 years and above with insufficiently

Page 23/67 controlled type 2 diabetes mellitus as an adjunct to diet and exercise The Committee discussed the issues identified in this application 3.3.8. Tovorafenib - Orphan - EMEA/H/C/006140 Ipsen Pharma; treatment of paediatric low-grade glioma (LGG) 3.3.9. Paltusotine - Orphan - EMEA/H/C/006636 Voisin Consulting Life Sciences; Maintenance treatment in adult patients with acromegaly The Committee discussed the issues identified in this application 3.3.10. Pertuzumab - EMEA/H/C/006583 treatment of breast cancer 3.3.11. Remibrutinib - EMEA/H/C/006313 treatment of chronic spontaneous urticaria in patients with inadequate response to H1 antihistamine

Page 24/67 3.3.12. INFLUENZA VACCINE - EMEA/H/C/006674 immunisation for the prevention of influenza disease 3.3.13. Autologous melanoma-derived tumour infiltrating lymphocytes, ex vivo-expanded - ATMP - EMEA/H/C/006563 treatment of melanoma The CHMP was updated on discussions at the CAT. The Committee was reminded of the status of this application and its remaining outstanding issues. The Committee endorsed a list of questions with a specific timetable, as adopted by CAT. 3.3.14. Tocilizumab - EMEA/H/C/006416 treatment of rheumatoid arthritis and other immunological conditions

Page 25/67 3.4. Update on on-going initial applications for Centralised procedure 3.4.1. Belumosudil - Orphan - EMEA/H/C/006421 Sanofi Winthrop Industrie; Treatment of chronic graft-versus host disease (cGVHD) after failure of at least two prior lines of systemic therapy. Scope: Update on the procedure Request by the applicant for an extension to the clock-stop to respond to the list of outstanding issues adopted in June 2025. List of Outstanding Issues adopted on 19.06.2025. List of Questions adopted on 30.01.2025. The CHMP noted the update on the procedure and denied the request by the applicant for an extension to the clock-stop to respond to the list of outstanding issues adopted in June 2025. 3.4.2. Golimumab - EMEA/H/C/006621 treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis Scope: Request by the applicant for an extension to the clock-stop to respond to the list of questions adopted in May 2025. List of questions adopted on 22.05.2025 respond to the list of questions adopted in May 2025. 3.4.3. Mavorixafor - Orphan - EMEA/H/C/006496 Treatment of WHIM syndrome Scope: Request by the applicant for an extension to the clock-stop to respond to the list of questions adopted in May 2025. List of questions adopted on 22.05.2025 The Committee agreed to the request by the applicant for an extension to the clock-stop to respond to the list of questions adopted in May 2025. 3.4.4. Plozasiran - Orphan - EMEA/H/C/006579 Arrowhead Pharmaceuticals Ireland Limited; treatment of familial chylomicronaemia syndrome (FCS). Scope: Request by the applicant for an extension to the clock-stop to respond to the list of

Page 26/67 questions adopted in June 2025. List of questions 19.06.2025 The Committee agreed to the request by the applicant for an extension to the clock-stop to respond to the list of questions adopted in June 2025. 3.5. Re-examination of initial application procedures under Article 9(2) of Regulation no 726/2004 3.5.1. Atropine sulfate FGK - Atropine - PUMA - EMEA/H/C/006385 FGK Representative Service GmbH; treatment of myopia in children aged 3 years and older Scope: Adoption of timetable, questions to the AHEG Known active substance (Article 8(3) of Directive No 2001/83/EC) Opinion adopted on 22.05.2025. List of Outstanding Issues adopted on 27.02.2025. List of Questions adopted on 19.09.2024. The CHMP adopted the timetable and the questions to the AHEG. 3.5.2. Austedo - Deutetrabenazine - EMEA/H/C/006371 Teva GmbH; treatment of tardive dyskinesia Scope: Request for re-examination, appointment of re-examination rapporteurs Opinion adopted on 19.06.2025. List of Outstanding Issues adopted on 27.02.2025. List of Questions adopted on 25.07.2024. The CHMP noted the request for re-examination and appointed re-examination rapporteur and re-examination co-rapporteur. 3.5.3. Kisunla - Donanemab - EMEA/H/C/006024 Eli Lilly Nederland B.V.; to slow disease progression in adult patients with Alzheimer’s disease (AD). Third party intervention Opinion adopted on 27.03.2025. List of Outstanding Issues adopted on 12.12.2024, 25.04.2024. List of Questions adopted on 14.12.2023. An oral explanation was held on 21 July 2025. The presentation by the applicant focused on

Page 27/67 authorisation by majority (17 out of 32) together with the CHMP assessment report and translation timetable. The divergent opinion (Daniela Philadelphy, Thalia Marie Blicher, Alexandre Moreau, Antonio Gómez Outes, Sol Ruiz, Emilia Mavrokordatou, Frantisek Drafi, Beata Maria Jakline Ullrich, Aris Angelis, Blanka Hirschlerová, Tomáš Radiměřský, Bruno Delafont, Peter Mol, Jayne Crowe, Outi Mäki-Ikola) was appended to the opinion. See 2.2 3.6. Initial applications in the decision-making phase No items 3.7. Withdrawals of initial marketing authorisation application 3.7.1. Lifileucel - ATMP - EMEA/H/C/004741 treatment of unresectable or metastatic melanoma Scope: Withdrawal of initial marketing authorisation application List of Outstanding Issues adopted on 16.05.2025. List of Questions adopted on 06.12.2024. The CHMP noted the withdrawal of the initial marketing authorisation application. 3.7.2. Aplidin - plitidepsin - Orphan - EMEA/H/C/004354 Pharma Mar, S.A.; treatment of multiple myeloma Restart the 2018 re-examination procedure relating to the initial marketing authorisation application for Aplidin following the adoption of Commission Implementing Decision C(2024) 4469 final of 28 June 2024 which revoked Commission Implementing Decision C(2018) 4831 final of 17 July 2018 refusing marketing authorisation for ‘Aplidin – plitidepsin’. That decision was revoked following the judgment of 14 March 2024 in D & A Pharma v Commission and EMA, C 291/22 P. An oral explanation was held on 23 July 2025. The presentation by the applicant focused on

Page 28/67 The MAH withdrew the re-examination application. See 2.2 3.7.3. Bifikafusp alfa / Onfekafusp alfa - EMEA/H/C/005651 neoadjuvant treatment of adult patients with locally advanced fully resectable melanoma Scope: Withdrawal of initial marketing authorisation application The CHMP noted the withdrawal of the initial marketing authorisation application. 3.7.4. Eflornithine – EMEA/H/C/006067 treatment of high-risk neuroblastoma responsive to prior multiagent, multimodality therapy Scope: Withdrawal of initial marketing authorisation application The CHMP noted the withdrawal of the initial marketing authorisation application. 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. Azacitidine Accord - Azacitidine - EMEA/H/C/005147/X/0021 Accord Healthcare S.L.U.; Rapporteur: Hrefna Gudmundsdottir, PRAC Rapporteur: Bianca Mulder Scope: “Extension application to introduce a new pharmaceutical form (film-coated tablet) associated with new strengths (200 and 300 mg) and new route of administration (oral use). The RMP (version 2.0) is updated in accordance.”

Page 29/67 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. Enzalutamide Viatris - Enzalutamide - EMEA/H/C/006299/X/0003 Viatris Limited; Rapporteur: Tomas Radimersky, PRAC Rapporteur: Maria del Pilar Rayon Scope: “Extension application to add a new strength of 160 mg for solution for film-coated tablets. The RMP (version 1.0) is updated in accordance.” The Committee discussed the issues identified in this application, relating to quality, clinical and non-clinical aspects. the list of outstanding issues and a specific timetable. 4.2.2. Hetlioz - Tasimelteon - Orphan - EMEA/H/C/003870/X/0039 Vanda Pharmaceuticals Netherlands B.V.; Rapporteur: Jayne Crowe, PRAC Rapporteur: Adam Przybylkowski Scope: “Extension application to introduce a new pharmaceutical form associated with new strength (4 mg/ml oral solution). The new formulation is indicated for the treatment of nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) in paediatric patients 3 to 15 years of age. The RMP (version 5.0) is updated in accordance.” orphan similarity aspects. the list of outstanding issues and a specific timetable. 4.2.3. Livmarli - Maralixibat - Orphan - EMEA/H/C/005857/X/0015 Mirum Pharmaceuticals International B.V.; Rapporteur: Janet Koenig, PRAC Rapporteur: Adam Przybylkowski Scope: “Extension application to introduce a new pharmaceutical form (tablet) associated with new strengths 10 mg, 15mg, 20 mg and 30 mg. The RMP (version 5.0) is updated in accordance.” Request by the applicant for an extension to the clock-stop to respond to the list of outstanding issues to be adopted in July 2025.

Page 30/67 The Committee discussed the issues identified in this application, relating to quality and the list of outstanding issues and a specific timetable. respond to the list of outstanding issues adopted in July 2025. 4.2.4. Pyrukynd - Mitapivat - Orphan - EMEA/H/C/005540/X/0010/G Agios Netherlands B.V.; Rapporteur: Alexandre Moreau, PRAC Rapporteur: Adam Przybylkowski Scope: “Extension application to introduce a new strength (100 mg film-coated tablet) associated with a new orphan indication for the “treatment of adult patients with non- transfusion-dependent and transfusion-dependent alpha- or beta-thalassaemia”. The extension application is grouped with a type II quality variation (C.I.4) to update of sections 4.2 and 5.2 of the SmPC in order to update pharmacokinetic information based on final results from study AG348-C-024 listed as a category 3 study in the RMP; this is a Phase 1, Open-label, Single-dose, Pharmacokinetic Study of Mitapivat in Subjects with Moderate Hepatic Impairment Compared to Matched Healthy Control Subjects with Normal Hepatic Function. The RMP (version 1.1) is updated in accordance.” the list of outstanding issues and a specific timetable. 4.2.5. Remsima - Infliximab - EMEA/H/C/002576/X/0149 Celltrion Healthcare Hungary Kft.; Rapporteur: Outi Mäki-Ikola, PRAC Rapporteur: Kimmo Jaakkola Scope: “Extension application to introduce a new pharmaceutical form (concentrate for solution for infusion) associated with a new strength (40 mg/ml).” List of Questions adopted on 25.04.2025. the list of outstanding issues and a specific timetable.

Page 31/67 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. Abrysvo - Respiratory syncytial virus vaccine (bivalent, recombinant) - EMA/X/0000258051 Rapporteur: Jayne Crowe Scope: Extension application to introduce a new pharmaceutical form Powder and solvent for solution for injection in multidose container. The Committee discussed the issues identified in this application, relating to quality and 4.3.2. Akynzeo - Fosnetupitant / Netupitant / Palonosetron - EMA/X/0000258060 Helsinn Birex Pharmaceuticals Limited Rapporteur: Finbarr Leacy, PRAC Rapporteur: Amelia Cupelli Scope: Extension application to introduce a new pharmaceutical form (300 mg / 0.5 ml oral suspension). 4.3.3. Camcevi – Leuprorelin - EMA/X/0000258054 Accord Healthcare S.L.U. Rapporteur: Johanna Lähteenvuo, PRAC Rapporteur: Amelia Cupelli Scope: Extension application to add a new strength of 21 mg for Leuproelin prolonged- release suspension for injection pre-filled syringe, for subcutaneous (SC) administration. The Committee discussed the issues identified in this application, relating to quality and clinical aspects

Page 32/67 4.3.4. Jorveza – Budesonide - EMA/X/0000257468 Dr. Falk Pharma GmbH Rapporteur: Janet Koenig, PRAC Rapporteur: Zane Neikena Scope: Extension application to introduce a new pharmaceutical form associated with new strength (0.2 mg/ml oral suspension). The new presentation is indicated for paediatric patients 2 to 17 years of age. 4.3.5. Lojuxta – Lomitapide - EMA/X/0000258068 Chiesi Farmaceutici S.p.A. Rapporteur: Patrick Vrijlandt, PRAC Rapporteur: Bianca Mulder Scope: Extension application to add a new strength of 2 mg hard capsules. This application is grouped with - type II variation (C.I.6.a): an Extension of Indication to include treatment of paediatric patients aged 5 years and older with homozygous familial hypercholesterolaemia (HoFH) for LOJUXTA, based on final results from the pivotal paediatric study APH-19; this is a phase 3, single-arm, open-label, international, multi-centre study to evaluate the efficacy and safety of lomitapide in paediatric patients with homozygous familial hypercholesterolaemia (HOFH) on stable lipid-lowering therapy. As a consequence, sections 4.1, 4.2, 4.4, 4.6, 4.8, 5.1, 5.2 and 5.3 of the SmPC are updated. The Annex II and Package Leaflet are updated accordingly. The RMP version 7.1 has also been submitted. In addition, the MAH took the opportunity to bring the PI in line with the latest QRD template version 10.4. 4.3.6. Nexviadyme - Avalglucosidase alfa - EMA/X/0000258013 Sanofi B.V. Rapporteur: Christian Gartner

Page 33/67 4.3.7. Olumiant – Baricitinib - EMA/X/0000257923 Eli Lilly Nederland B.V. Rapporteur: Peter Mol, PRAC Rapporteur: Adam Przybylkowski Scope: Extension application to introduce a new pharmaceutical form (oral suspension) associated with a new strength (2 mg/ml). The Committee discussed the issues identified in this application EMA/X/0000257923. 4.3.8. Scemblix – Asciminib - EMA/X/0000256688 Novartis Europharm Limited Rapporteur: Jante Koenig, Co-Rapporteur: Peter Mol, PRAC Rapporteur: Eva Jirsová Scope: Extension application to introduce a new strength (100 mg film-coated tablets) grouped with a type II variation (C.I.6.a) to add a new indication (treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase (Ph+ CML-CP) harbouring the T315I mutation), based on final results from study CABL001X2101 and study CABL001A2004. Study CABL001X2101 is a Phase I, multicentre, open-label, dose escalation FIH study to define the MTD/RDEs, to characterize safety and tolerability, and to assess the PK profile and preliminary evidence of efficacy of asciminib given as single agent or in combination with either nilotinib or imatinib or dasatinib in patients with Ph+ CML or Ph+ ALL. Study CABL001A2004 assessed the real-world effectiveness of asciminib and treatment patterns in patients with Chronic Myeloid Leukaemia with T315I mutation. As a consequence, sections 1, 2, 3, 4, 5, 6 and 8 of the SmPC are updated. The Package Leaflet and Labelling are updated in accordance. Version 3.0 of the RMP has also been submitted. As part of the application the MAH is requesting a 1-year extension of the market protection. 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

Page 34/67 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. Alhemo – Concizumab - EMA/VR/0000244862 Novo Nordisk A/S Rapporteur: Patrick Vrijlandt, Co-Rapporteur: Daniela Philadelphy, PRAC Rapporteur: Marie Louise Schougaard Christiansen Scope: Extension of indication to include treatment of haemophilia A without inhibitors and haemophilia B without inhibitors for ALHEMO based on final results from study NN7415- 4307; this is an interventional study to investigate efficacy and safety of concizumab prophylaxis in patients with haemophilia A or B without inhibitors. As a consequence, 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 2.0 of the RMP has also been submitted. In addition, the MAH took the opportunity to introduce minor changes to the PI. 5.1.2. BAQSIMI – Glucagon - EMA/VR/0000244909 Amphastar France Pharmaceuticals Rapporteur: Karin Janssen van Doorn, PRAC Rapporteur: Eamon O Murchu Scope: Extension of indication to include treatment of severe hypoglycaemia in paediatric patients aged 1 and over with diabetes mellitus for BAQSIMI, based on final results from study I8R-MC-IGBO; this is an Open-Label, Multi-Center, Single-Dose Study to Assess the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Nasal Glucagon in Paediatric Patients with Type 1 Diabetes Aged 1 to <4 years; As a consequence, 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 1.0 of the RMP has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity to introduce a correction in the Package Leaflet.

Page 35/67 5.1.3. BESPONSA - Inotuzumab ozogamicin - EMA/VR/0000257310 Rapporteur: Filip Josephson, PRAC Rapporteur: Gabriele Maurer Scope: Extension of indication to include treatment of paediatric patients 1 year and older with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukaemia (ALL) for BESPONSA, based on final results from studies ITCC-059 (WI203581) and INO- Ped-ALL-1 (WI235086). Study WI203581 is a Phase 1/2, multicentre, European, multi-cohort, open-label study in paediatric patients (≥1 and <18 years of age) with R/R CD22-positive ALL; Study WI235086 is an open-label, Phase 1 study to assess safety and tolerability of InO in Japanese paediatric patients with R/R CD22-positive AL. As a consequence, sections 4.1, 4.2, 4.8, 5.1 and 6.6 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 4.0 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. 5.1.4. Breyanzi - Lisocabtagene maraleucel – ATMP – EMA/VR/0000265024 Bristol-Myers Squibb Pharma EEIG CAT Rapporteur: Concetta Quintarelli, CHMP Coordinator: Paolo Gasparini Scope: A grouped application comprised of two Type II variations, as follows: Type II (C.I.6): Extension of indication to include the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor for BREYANZI, based on results from the pivotal Study 017001 MCL Cohort (TRANSCEND-NHL-001); this is a Phase 1, Multicentre, Open-Label Study of JCAR017, CD19-targeted Chimeric Antigen Receptor (CAR) T Cells, for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL). As a consequence, sections 4.1, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package leaflet is updated in accordance. Version 7.0 of the RMP has also been submitted. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI and to update the list of local representatives in the Package Leaflet. Quality variation

Page 36/67 The CHMP was updated on discussions at the CAT. The Committee discussed the issues identified in this application. The Committee discussed the issues identified in this application, relating to quality aspects . The Committee endorsed a request for supplementary information with a specific timetable, as adopted by CAT. 5.1.5. Cejemly – Sugemalimab - EMA/VR/0000261157 Cstone Pharmaceuticals Ireland Limited Rapporteur: Filip Josephson, PRAC Rapporteur: Petar Mas Scope: Extension of indication to include the treatment of unresectable stage III non‑small‑cell lung cancer (NSCLC) with no sensitising EGFR mutations, or ALK, ROS1 genomic tumour aberrations in adults whose disease has not progressed following concurrent or sequential platinum-based chemoradiotherapy for CEJEMLY, based on final results from study CS1001-301; this is a Phase III, multicentre, randomised, double-blind, placebo-controlled study assessing the efficacy and safety of sugemalimab as consolidation therapy versus placebo in participants with locally advanced or unresectable stage III NSCLC who have not progressed after concurrent or sequential chemoradiotherapy. 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 2.0 of the RMP has also been submitted. 5.1.6. Clopidogrel Zentiva - Clopidogrel - EMEA/H/C/000975/II/0092 Zentiva k.s.; Rapporteur: Fátima Ventura, PRAC Rapporteur: Carla Torre Scope: “Extension of indication to include, in combination with acetylsalicylic acid (ASA), patients with ST segment elevation acute myocardial infarction (STEMI) who are undergoing percutaneous coronary intervention (PCI) for CLOPIDOGREL ZENTIVA. As a consequence, sections 4.1, 4.2, 4.4 and 5.1 of the SmPC are updated. Version 0.1 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, introduce minor editorial changes to the PI and bring it in line with the latest QRD template version 10.4.” Request for Supplementary Information adopted on 25.04.2025.

Page 37/67 5.1.7. CRYSVITA – Burosumab - EMA/VR/0000263400 Kyowa Kirin Holdings B.V. Rapporteur: Kristina Dunder Scope: Extension of indication to include treatment of X-linked hypophosphataemia (XLH) in paediatric patients from birth to less than 1 year of age for CRYSVITA, based on final results from study BUR-CL207; this is a phase 1/2 Open-label, Multicentre, Non-randomized Study to Evaluate Safety, Pharmacodynamics, Pharmacokinetics and Effect of Burosumab in Paediatric Patients from Birth to Less than 1 Year of Age with XLH; 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. 5.1.8. Elucirem/ Vueway – Gadopiclenol - EMA/VR/0000249008 Guerbet, Bracco Imaging S.p.A Rapporteur: Patrick Vrijlandt, PRAC Rapporteur: Martin Huber Scope: Extension of indication to include treatment of new population (0 to 2 years of age patients) for ELUCIREM / VUEWAY, based on final results from study GDX-44-015; this is a phase ii clinical study concerning gadopiclenol pharmacokinetics, safety and efficacy in paediatric patients < 2 years of age undergoing contrast-enhanced MRI; extension of indication is also supported with the non-clinical data. 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 0.4 of the RMP has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity to remove Annex IV from the PI. As part of the application, the MAH is requesting a 1-year extension of the market protection. 5.1.9. Eylea – Aflibercept - EMA/VR/0000264981 Bayer AG Rapporteur: Jean-Michel Race, PRAC Rapporteur: Zoubida Amimour Scope: A grouped application comprised of two Type II Variations, as follows: C.I.6: Extension of indication to include the treatment of visual impairment due to macular oedema secondary to retinal vein occlusion (branch, central and hemiretinal RVO) for EYLEA, based on results from study 22153 (QUASAR); this is a randomized, double- masked, active-controlled Phase 3 study of the efficacy and safety of aflibercept 8 mg in macular oedema secondary to retinal vein occlusion. 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

Page 38/67 accordingly. The RMP version 36.1 has also been submitted. C.I.4: Update of section 4.2 of the SmPC in order to change posology recommendations of the approved indications nAMD and DME based on the results from study 22153 (QUASAR) and post-hoc analysis of the pivotal studies 20968 (PULSAR), 21091 (PHOTON) and Phase II study 21086 (CANDELA). 5.1.10. Gazyvaro – Obinutuzumab - EMA/VR/0000244907 Roche Registration GmbH Rapporteur: Boje Kvorning Pires Ehmsen, PRAC Rapporteur: Mari Thorn Scope: Extension of indication to include treatment of adult patients with active lupus nephritis who are receiving standard therapy for GAZYVARO, based on results from study Regency (CA41705). This is an ongoing, Phase III, randomized, double-blind, placebo- controlled, multicentre study evaluating the efficacy and safety of obinutuzumab administered at standard infusion rates in patients with ISN/RPS 2003 Class III or IV lupus nephritis treated with standard-of-care therapy. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1, 5.2 and 6.6 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 11 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. 5.1.11. Iclusig – Ponatinib - EMA/VR/0000263550 Incyte Biosciences Distribution B.V. Rapporteur: Filip Josephson, Co-Rapporteur: Ewa Balkowiec Iskra, PRAC Rapporteur: Mari Thorn Scope: Extension of indication to include treatment of adult patients with newly-diagnosed Ph+ ALL for ICLUSIG, based on interim results from study Ponatinib-3001 (PhALLCON); this is a phase 3, randomized, open-label, multicentre study comparing ponatinib versus imatinib, administered in combination with reduced intensity chemotherapy, in patients with newly diagnosed Ph+ ALL; supportive data were derived from two single-arm, open-label clinical studies (AP24534 11 001 in combination with chemotherapy and INCB 84344-201 as monotherapy). 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 23.2 of the RMP has also been submitted. In addition, earlier approved updates were incorporated to the PI.

Page 39/67 pharmacovilance aspects. 5.1.12. Invokana - Canagliflozin - EMEA/H/C/002649/II/0069 Janssen-Cilag International N.V.; Rapporteur: Janet Koenig, PRAC Rapporteur: Martin Huber Scope: “Extension of indication to include treatment of paediatric patients with type 2 diabetes mellitus aged 10 years old and older for INVOKANA, based on final results from study JNJ-28431754DIA3018 as well as study JNJ-28431754DIA1055. Study JNJ- 28431754DIA3018 is a double-blind, placebo-controlled, 2-arm, parallel-group, multicentre Phase 3 study in participants with T2DM >10 and <18 years of age who had inadequate glycemic control (i.e., HbA1c of >6.5% to <11.0%). As a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 13.1 of the RMP has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity to introduce minor changes to the PI and update the list of local representatives in the Package Leaflet.” Request for Supplementary Information adopted on 27.03.2025, 14.11.2024. 5.1.13. Keytruda – Pembrolizumab - EMA/VR/0000245108 Merck Sharp & Dohme B.V. Rapporteur: Paolo Gasparini, PRAC Rapporteur: Bianca Mulder Scope: Extension of indication to include, KEYTRUDA as monotherapy, for the treatment of resectable locally advanced head and neck squamous cell carcinoma (HNSCC) as neoadjuvant treatment, continued as adjuvant treatment in combination with radiation therapy with or without platinum-containing chemotherapy and then as monotherapy in adults, based on the results of study P689V01MK3475 (KEYNOTE-689); this is a Phase 3, randomised, open-label study evaluating pembrolizumab as neoadjuvant therapy and in combination with standard of care as adjuvant therapy for stage III or IVA, resectable, locoregionally advanced head and neck squamous cell carcinoma. Consequently, sections 4.1, 4.2, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. The RMP version 48.1 has also been submitted. In addition, the MAH took the opportunity to introduce some minor editorial changes to the PI.

Page 40/67 5.1.14. LIBTAYO – Cemiplimab - EMA/VR/0000264999 Regeneron Ireland Designated Activity Company Rapporteur: Boje Kvorning Pires Ehmsen, PRAC Rapporteur: Bianca Mulder Scope: Extension of indication to include adjuvant treatment of adult patients with Cutaneous Squamous Cell Carcinoma (CSCC) at high risk of recurrence after surgery and radiation for LIBTAYO, based on interim results from study R2810-ONC-1788; this is a phase 3, randomized, placebo-controlled, double-blind study of adjuvant cemiplimab versus placebo after surgery and radiation therapy in patients with high risk CSCC; As a consequence, sections 4.1, 4.2, 4.8, 5.1, and 6.6 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 4.2 of the RMP has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the warnings for the excipients proline and polysorbate to reflect EU guidance (Section 4.4), and also updated Annex IID of the PI in line with the updates made to the RMPv4.2 to consolidate the aRMMs. 5.1.15. mRESVIA - Respiratory syncytial virus mRNA vaccine (nucleoside modified) - EMA/VR/0000248175 Moderna Biotech Spain S.L. Rapporteur: Jan Mueller-Berghaus, PRAC Rapporteur: Jean-Michel Dogné Scope: To modify the approved therapeutic indication to include active immunisation for the prevention of lower respiratory tract disease (LRTD) caused by Respiratory Syncytial Virus in individuals 18 through 59 years of age who are at increased risk for LRTD caused by RSV for mRESVIA, based on results from Study mRNA-1345-P303 (Part A) - A Phase 3 Study to Evaluate the Immunogenicity and Safety of mRNA-1345, an mRNA Vaccine Targeting Respiratory Syncytial Virus, in High-risk Adults. As a consequence, sections 4.1, 4.6, 4.8 and 5.1 of the SmPC and the corresponding sections of the Package Leaflet are updated accordingly. The updated RMP Version 1.0 has also been submitted. In addition, the MAH took the opportunity to implement editorial changes to the PI. 5.1.16. Neuraceq - Florbetaben (18F) - EMA/VR/0000227744 Life Molecular Imaging GmbH Rapporteur: Antonio Gomez-Outes, PRAC Rapporteur: Martin Huber

Page 41/67 Scope: Update of section 4.5 of the SmPC to reflect new preclinical data and editorial update of section 5.1. The Package Leaflet is also updated with discontinuation of the paper copy SmPC. In addition, Annex IID is updated with deletion of additional risk minimisation measures. The RMP version 7.0 is agreed. The CHMP noted the Q&A document. 5.1.17. Noxafil – Posaconazole - EMA/VR/0000263360 Merck Sharp & Dohme B.V. Rapporteur: Alexandre Moreau, PRAC Rapporteur: Zoubida Amimour Scope: Extension of indication for NOXAFIL to include treatment of patients two years of age and older for invasive aspergillosis (IA) based on final results from study MK-5592-104 (P104); this is a Phase 2, open-label, noncomparative clinical study that evaluated the safety, efficacy, and PK of POS in paediatric participants aged 2 to <18 years with IA. As a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet and Labelling are updated in accordance. Version 18.1 of the RMP has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity to implement editorial changes to the PI. 5.1.18. Recarbrio - Imipenem / Cilastatin / Relebactam - EMA/VR/0000265089 Merck Sharp & Dohme B.V. Rapporteur: Filip Josephson, Co-Rapporteur: Alar Irs, PRAC Rapporteur: Adam Przybylkowski Scope: Extension of indication to extend the approved adult indications for RECARBRIO to include treatment of paediatric population from birth to <18 years of age, based on final results from two paediatric studies (MK-7655A-021 and MK-7655A-020); phase 2/3 study MK-7655A-021 addressed safety, tolerability, efficacy and PK, and phase 1b study MK- 7655A-020 addressed PK, safety, and tolerability of MK-7655A in paediatric subjects from birth to less than 18 years of age with confirmed or suspected gram-negative infections. As a consequence, sections 4.1, 4.2, 4.8, 5.1, 5.2, and 6.6 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 2.1 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 and implement minor editorial corrections.

Page 42/67 non-clinical aspects. 5.1.19. Scemblix – Asciminib - EMA/VR/0000265010 Novartis Europharm Limited Rapporteur: Janet Koenig, PRAC Rapporteur: Eva Jirsová Scope: A grouped application consisting of: C.I.6.a: Extension of indication to include treatment of adult patients with newly diagnosed or previously treated Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML) in chronic phase (CP) for SCEMBLIX, based on primary and key secondary analysis results from study CABL001J12301 (ASC4FIRST, J12301); this is an ongoing Phase III, multi-centre, open-label, randomized study of oral asciminib (80 mg once daily, q.d.) versus Investigator selected tyrosine kinase inhibitor (TKI) in patients with newly diagnosed Ph+ CML-CP, with the primary and key secondary objectives to compare the major molecular response (MMR) rates at Week 48 and Week 96, respectively. As a consequence, sections 4.1, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated accordingly. RMP version 4.0 has also been submitted. As part of the application the MAH is requesting a 1-year extension of the market protection. C.I.4: Update of sections 4.2, 4.5, 5.1, 5.2 and 5.3 of the SmPC in order to introduction of a new posology regimen based on results from studies CABL001J12301 and CABL001A2302 (ASC4OPT, A2302). CABL001A2302 is an ongoing Phase IIIb, multi-centre, open-label, treatment optimization study of oral asciminib (80 mg daily, randomized to 40 mg b.i.d. or 80 mg q.d.) in patients with Ph+ CML-CP previously treated with two or more TKIs, with the primary objective to estimate the MMR rate at Week 48 of all the patients (40 mg b.i.d. and 80 mg q.d.) with no evidence of MMR at baseline. The Package Leaflet is updated accordingly. RMP version 4.0 has also been submitted. non-clinical aspects . 5.1.20. SIRTURO – Bedaquiline - EMA/VR/0000249065 Janssen Cilag International Rapporteur: Filip Josephson, PRAC Rapporteur: Karin Bolin Scope: Extension of indication to include treatment of paediatric patients (2 years to less than 5 years of age and weighing at least 7 kg) with pulmonary tuberculosis (TB) due to Mycobacterium tuberculosis resistant to at least rifampicin and isoniazid, for SIRTURO, based on the Week 24 primary analysis from Cohort 3 (≥2 to <5 years of age) of Study TMC207-C211; this is an open-label, multicentre, single-arm study to evaluate pharmacokinetics, safety/tolerability, antimycobacterial activity and dose selection of

Page 43/67 bedaquiline in children (birth to <18 years) with multidrug-resistant-TB (MDR-TB). Long- term follow-up to Week 120 in participants of Cohort 1 (≥12 to <18 years of age) and Cohort 2 (≥5 to <12 years of age) have also been submitted. As a consequence, 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 11.1 of the RMP has also been approved. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the list of local representatives in the Package Leaflet and introduce minor changes to the PI. 5.1.21. Sogroya – Somapacitan - EMA/VR/0000264734 Novo Nordisk A/S Rapporteur: Patrick Vrijlandt, PRAC Rapporteur: Martin Huber Scope: Grouped extension of indication application to include treatment of children born small for gestational age (SGA), Noonan syndrome (NS) and idiopathic short stature (ISS) for SOGROYA, based on interim results from the pivotal, confirmatory phase 3 study NN8640-4467 supported by the phase 3 study NN8640-4469 and the phase 2 study NN8640-4245. Study 4467 is a study comparing the effect and safety of once weekly dosing of somapacitan with daily Norditropin as well as evaluating long-term safety of somapacitan in a basket study design in children with short stature either born small for gestational age or with Turner syndrome, Noonan syndrome, or idiopathic short stature. Study 4469 is a study evaluating the safety and efficacy of once-weekly dosing of somapacitan in a basket study design in paediatric participants with short stature either born small for gestational age or with turner syndrome, Noonan syndrome or idiopathic short stature. Study 4245 is a dose-finding trial evaluating the effect and safety of once-weekly treatment of somapacitan compared to daily Norditropin in children with short stature born small for gestational age with no catch-up growth by 2 years of age or older. As a consequence, 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 4.0 of the RMP has also been submitted. Furthermore, the PI is brought in line with the latest QRD template version 10.4. As part of the application, the MAH is requesting a 1- year extension of the market protection. 5.1.22. Taltz - Ixekizumab - EMEA/H/C/003943/II/0053 Eli Lilly and Co (Ireland) Limited; Rapporteur: Kristina Dunder, PRAC Rapporteur: Gabriele Maurer

Page 44/67 Scope: “Extension of indication for TALTZ to include treatment alone or in combination with methotrexate, of active JPsA and ERA in patients 6 years of age and older and with a body weight of at least 25 kg, who have had an inadequate response to, or who are intolerant of, conventional therapy, based on week 16 results from study I1F-MC-RHCG. As a consequence, 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 8.2 of the RMP has also been updated. Furthermore, the PI is in line with the latest QRD template version 10.4.” Request for Supplementary Information adopted on 27.03.2025, 14.11.2024. 5.1.23. Tevimbra - Tislelizumab - EMEA/H/C/005919/II/0018 Beone Medicines Ireland Limited; Rapporteur: Jan Mueller-Berghaus, PRAC Rapporteur: Bianca Mulder Scope: “Extension of indication for Tevimbra in combination with platinum-containing chemotherapy as neoadjuvant treatment and then continued as monotherapy as adjuvant treatment, for the treatment of adult patients with resectable NSCLC based on interim results from study BGB-A317-315. Study BGB-A317-315 is a phase 3 randomized, placebo- controlled, double-blind study to compare the efficacy and safety of neoadjuvant treatment with tislelizumab plus platinum-based doublet chemotherapy followed by adjuvant tislelizumab versus neoadjuvant treatment with placebo plus platinum-based doublet chemotherapy followed by adjuvant placebo in patients with resectable Stage II or IIIA NSCLC. As a consequence, sections 4.1, 4.2, 5.1, and 6.6 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 6.0 of the RMP has also been agreed.” Request for Supplementary Information adopted on 27.03.2025. 5.1.24. TEZSPIRE – Tezepelumab - EMA/VR/0000245013 AstraZeneca AB Rapporteur: Finbarr Leacy, Co-rapporteur: Ewa Balkowiec Iskra, PRAC Rapporteur: Eva Jirsová Scope: Extension of indication to include treatment of Chronic Rhinosinusitis with Nasal

Page 45/67 Polyps (CRSwNP) for Tezspire, based on results from study WAYPOINT (D5242C00001); this is a global, multicentre, randomised, double-blind, parallel-group, placebo-controlled study that evaluated the efficacy and safety of tezepelumab compared with placebo in the treatment of CRSwNP. As a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet and Labelling are updated in accordance. Version 4.1 of the RMP has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity to implement editorial changes and to update the PI and the Package Leaflet in accordance with the latest EMA excipients guideline. The Committee discussed the issues identified in this application, relating to clinical aspects 5.1.25. VEYVONDI - Vonicog alfa - EMA/VR/0000264863 BAXALTA INNOVATIONS GmbH Rapporteur: Jan Mueller-Berghaus, Co-Rapporteur: Daniela Philadelphy, PRAC Rapporteur: Mari Thorn Scope: Extension of indication to include treatment of haemorrhage in children aged less than 18 years for VEYVONDI, based on results from studies 071102 and SHP677-304. Study 071102 is a phase 3, prospective, multicentre, uncontrolled, open-label clinical study to determine the efficacy, safety, and tolerability of rVWF with or without ADVATE in the treatment and control of bleeding episodes, the efficacy and safety of rVWF in elective and emergency surgeries, and the pharmacokinetics (PK) of rVWF in children diagnosed with severe VWD; study SHP677-304 is a phase 3B, prospective, open-label, uncontrolled, multicentre study on long term safety and efficacy of vonicog alfa in paediatric and adult subjects with severe VWD. As a consequence, sections 4.1, 4.2, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated accordingly. Version 6.0 of the RMP has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity to bring the PI in line with the latest QRD template version 10.4, to update the PI in accordance with the latest EMA excipients guideline, and to implement editorial changes to the PI. 5.1.26. Xerava – Eravacycline - EMA/VR/0000265697 Paion Pharma GmbH Rapporteur: Filip Josephson Scope: Extension of indication to include treatment of complicated intra-abdominal infections (cIAI) from the age of 8 years and older for XERAVA, based on final results from study TP-434-028; this is a phase 1, open-label, multicentre study to determine the pharmacokinetics and safety of intravenous eravacycline in children with suspected or confirmed bacterial infection; As a consequence, sections 4.1, 4.2, 5.1, 5.2, and 6.6 of the

Page 46/67 SmPC are updated. The Package Leaflet is updated in accordance. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the list of local representatives in the Package Leaflet. Furthermore, the PI is brought in line with the latest QRD template version 10.4. 5.2. Update on on-going Type II variation; variation of therapeutic indication procedure according to Commission Regulation (EC) No 1234/2008 No items 5.3. Re-examination of Type II variation; variation of therapeutic indication procedure according to Commission Regulation (EC) No 1234/2008 No items 6. Medical devices 6.1. Ancillary medicinal substances - initial consultation 6.2. Ancillary medicinal substances – post-consultation update No items 6.3. Companion diagnostics - initial consultation 6.3.1. In vitro diagnostic medical device - EMEA/H/D/006768 qualitative determination of antibodies to adeno-associated virus serotype 74 (AAVrh74) in human serum and/or plasma The CHMP was updated on discussions at the CAT. The Committee endorsed the list of questions with a specific timetable as adopted by the CAT.

Page 47/67 6.3.2. VENTANA HER2 Dual ISH DNA Probe Cocktail RxDx - In vitro diagnostic medical device - EMEA/H/D/006723 Roche Diagnostics GmbH; to determine HER2 gene status by enumeration of the ratio of the HER2 gene to Chromosome 17 by light microscopy List of questions adopted on 19.06.2025. 6.3.3. VENTANA HER2 (4B5) Rabbit Monoclonal Primary Antibody RxDx - In vitro diagnostic medical device - EMEA/H/D/006724 Roche Diagnostics GmbH; semi-quantitative detection of HER2 antigen by immunohistochemistry (IHC) in sections of formalin-fixed, paraffin-embedded breast carcinoma, gastric carcinoma, and biliary tract cancer List of questions adopted on 19.06.2025. 6.4. Companion diagnostics – follow-up consultation 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

Page 48/67 8. Pre-submission issues 8.1. Pre-submission issue 8.1.1. Acoziborole - Article 58 – H0006686 Treatment of Human African Trypanosomiasis (HAT or sleeping sickness) caused by T.b. gambiense Scope: Briefing note and the Rapporteurs’ recommendation on the request for accelerated assessment. The CHMP agreed to the request for accelerated assessment and adopted the briefing note and Rapporteurs’ recommendation on the Request for Accelerated Assessment. 8.2. Priority Medicines (PRIME) Information related to priority medicines cannot be released at present time as these contain commercially confidential information. The CHMP adopted the recommendations for PRIME eligibility. The individual outcomes are listed in the PRIME Monthly Report on the EMA website, in the PRIME homepage, under Outcome of eligibility section. 9. Post-authorisation issues 9.1. Post-authorisation issues 9.1.1. Amvuttra - Vutrisiran - Orphan - EMEA/H/C/005852/II/0015 Alnylam Netherlands B.V.; Rapporteur: Janet Koenig, Co-Rapporteur: Fátima Ventura, PRAC Rapporteur: Liana Martirosyan Scope: Revised assessment report Opinion adopted on 25.04.2025. Request for Supplementary Information adopted on 30.01.2025. The CHMP adopted the revised assessment report. 9.1.2. Tecovirimat SIGA – Tecovirimat - EMA/S/0000248804 Siga Technologies Netherlands B.V.

Page 49/67 Rapporteur: Jayne Crowe, PRAC Rapporteur: Martin Huber Scope: Annual reassessment In the evaluation of the annual re-assessment new efficacy data have emerged from recent clinical trials suggesting a lack of effectiveness in the treatment of mpox. The findings from these emerging and forthcoming data need to be reviewed, taking into account all available data, to determine whether there is an impact on the benefit-risk balance in the authorised indications. In view of the above, the EC initiated an Article 20 referral (EC) No 726/2004 and requests the CHMP to assess the above concerns and their impact on the benefit risk balance for the centrally authorised medicinal product Tecovirimat SIGA. See 10.1.3 9.1.3. WS2780 Riltrava Aerosphere-EMEA/H/C/005311/WS2780/0017 Trixeo Aerosphere-EMEA/H/C/004983/WS2780/0024 AstraZeneca AB Lead Rapporteur: Finbarr Leacy, Lead PRAC Rapporteur: Jan Neuhauser Request for Supplementary Information adopted on 22.05.2025, 30.01.2025. 9.1.4. Fluenz Tetra - Influenza vaccine (live attenuated, nasal) – EMEA/H/C/002617 AstraZeneca AB; Prophylaxis of influenza in individuals 24 months to less than 18 years. Rapporteur: Christophe Focke, Co-Rapporteur: Ingrid Wang Scope: Withdrawal of marketing authorisation The CHMP noted the withdrawal of the marketing authorisation. 9.1.5. Volibris – Ambrisentan - EMA/VR/0000266441 Glaxosmithkline (Ireland) Limited Rapporteur: Antonio Gomez-Outes

Page 50/67 Scope: Update of sections 4.2 and 5.3 of the SmPC in order to update the recommendations for the paediatric population, based on non-clinical data. In addition, the MAH took the opportunity to introduce minor editorial and formatting changes to the PI. The Committee discussed the issues identified in this application, relating to non-clinical and 9.1.6. COMIRNATY - COVID-19 mRNA vaccine - EMA/VR/0000275515 BioNTech Manufacturing GmbH Rapporteur: Filip Josephson 9.1.7. BIMERVAX - COVID-19 vaccine (recombinant, adjuvanted) - EMA/VR/0000279224 Hipra Human Health S.L. Rapporteur: Beata Maria Jakline Ullrich 9.1.8. Spikevax - COVID-19 mRNA vaccine - EMA/VR/0000278795 Moderna Biotech Spain S.L. Rapporteur: Jan Mueller-Berghaus

Page 51/67 9.1.9. Holoclar - ex vivo expanded autologous human corneal epithelial cells containing stem cells – ATMP - EMEA/H/C/002450/R/0058 Holostem S.r.l. Rapporteur: Egbert Flory, CHMP coordinators: Jan Mueller-Berghaus and Paolo Gasparini Scope: Revised opinion adopted via written procedure on 01.07.2025. The CHMP noted the written procedure. 9.1.10. Evrysdi – Risdiplam – EMEA/H/C/005145 Roche Registration GmbH; treatment of spinal muscular atrophy (SMA) Rapporteur: Fatima Ventura, Co-Rapporteur: Paolo Gasparini Scope: DHPC letter and Communication plan for QD2025-240 The CHMP adopted the DHPC letter and the communication plan for QD2025-240. 9.1.11. Inrebic - Fedratinib - EMEA/H/C/005026/II/0027, Orphan Bristol-Myers Squibb Pharma EEIG Rapporteur: Peter Mol Scope: Withdrawal of Type II variation Request for Supplementary Information adopted on 27.02.2025. The Committee noted the withdrawal of the Type II variation. 10. Referral procedures 10.1. Procedure for Centrally Authorised products under Article 20 of Regulation (EC) No 726/2004 10.1.1. Oxbryta - Voxelotor - EMEA/H/A-20/1538/C/004869/0014 Referral Rapporteur: Patrick Vrijlandt, Referral Co- Rapporteur: Alexandre Moreau Scope: Revised timetable, draft list of experts for AHEG The EC initiated a procedure under Article 20 of Regulation (EC) No 726/2004 to assess the benefit-risk balance of Oxbryta in its authorised indication. The initiation of the review

Page 52/67 follows an imbalance of deaths between voxelotor and placebo observed in clinical trials. The findings from these emerging safety data need to be further reviewed, taking into account all available data, to determine whether there is an impact on the benefit-risk balance of Oxbryta in its authorised indication. List of outstanding issues adopted 22.05.2025, 12.12.2024. List of questions adopted on 29.07.2024 The CHMP adopted the revised timetable and draft list of experts for AHEG. 10.1.2. IXCHIQ - Chikungunya vaccine (live) - EMA/REF/0000269473 Valneva Austria GmbH Referral PRAC Rapporteur: Gabriele Maurer Review of the benefit-risk balance following procedure triggered by the European Commission (EC) under Article 20 of Regulation (EC) No 726/2004 resulting from pharmacovigilance data; PRAC recommendation. Based on the recommendation prepared by the PRAC, the Committee adopted a positive opinion by consensus. 10.1.3. Tecovirimat SIGA – Tecovirimat - EMA/REF/0000287477 Siga Technologies Netherlands B.V. Referral Rapporteur: Jayne Crowe, Referral Co-Rapporteur: Vilma Petrikaite Scope: Start of procedure, appointment of rapporteurs, list of questions, timetable The European Commission (EC) initiated a procedure under Article 20 of Regulation (EC) No 726/2004 and requested the Agency/CHMP to assess the benefit-risk balance of Tecovirimat SIGA. The review was prompted by emerging data from clinical trials, which raised concerns about a potential lack of efficacy. These findings need to be reviewed in the context of all available data and their potential impact on the benefit-risk of Tecovirimat SIGA in its authorised indications. In addition, the EC requests the Agency/CHMP to give its opinion, as soon as possible, as to whether temporary measures are necessary to ensure the safe and effective use of this medicinal product. The CHMP appointed as referral rapporteur Jayne Crowe (IE) and Vilma Petrikaite (LT) as referral Co-Rapporteur. The CHMP agreed that no temporary measures were necessary at this stage. The CHMP considered at this point that a detailed assessment of further data from the trials raising concern of a possible lack efficacy in the context of all available data on Tecovirimat SIGA was necessary, before making recommendations on its authorised use. The CHMP adopted a list of questions with a procedural timetable.

Page 53/67 10.2. Requests for CHMP Opinion under Article 5(3) of Regulation (EC) No 726/2004 10.2.1. Colistimethate sodium (CMS) – EMEA/H/A-5(3)/1524 Various MAHs Referral Rapporteur: Janet Koenig, Referral Co-Rapporteur: Ewa Balkowiec Iskra Scope: Revised list of outstanding issues Review of the ratio of polymyxins E1 and E2 in colistin starting material and of the (sulfomethylation) composition profile of CMS finished product. List of outstanding issues adopted on 21.03.2024, 22.02.2024, 22.05.2025. List of questions adopted on 22.06.2023. The CHMP adopted a revised 2 nd list of outstanding issues. 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

Page 54/67 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 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 July 2025 Early Notification System on envisaged CHMP/CMDh outcome accompanied by communication to the general public. 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.

Page 55/67 13. Innovation Task Force 13.1. Minutes of Innovation Task Force No items 13.2. Innovation Task Force briefing meetings Information related to briefing meetings taking place with applicants cannot be released at the present time as it is deemed to contain commercially confidential information. 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. Vote by Proxy Jan Mueller-Berghaus (Co-opted member) gave proxy to Janet Koenig (DE) for the entire duration of the meeting. Simona Badoi (RO) gave a proxy to Ewa Balkowiec-Iskra (PL) for the entire duration of the meeting. Alar Irs (EE) gave a proxy to John Jospeh Borg (MT) for the Tuesday session of the meeting. 14.1.2. CHMP membership No items 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

Page 56/67 Reports (EURD list) for July 2025 The CHMP adopted the EURD list. 14.2.2. Paediatric Committee (PDCO) PIPs reaching D30 at July 2025 PDCO The CHMP note the PIPs reaching D30 at the July 2025 PDCO. Agenda from the PDCO meeting held on 22-25 July 2025 The CHMP noted the agenda. 14.3. Coordination with EMA Working Parties/Working Groups/Drafting Groups 14.3.1. Biologics Working Party (BWP) Chair: Sean Barry, Vice-Chair: Andreea Barbu The CHMP adopted the BWP reports. 14.3.2. Scientific Advice Working Party (SAWP) Chair: Paolo Foggi Report from the SAWP meeting held on 07-10 July 2025. Table of conclusions Scientific advice letters: Information related to scientific advice letters cannot be released at present time as these contain commercially confidential information. 14.3.3. The CHMP noted the update.Election of Oncology Working Party Vice-Chair The position of vice-chair is currently being held by Olli Tenhunen (FI). Action: For election Nomination(s) received The CHMP re-elected Olli Tenhunen (FI) as vice-chair of the Oncology Working Party.

Page 57/67 14.3.4. Election of 3Rs Working Party Chair and Vice-Chair Action: For election Nomination(s) received The CHMP elected Sonja Beken (BE) as chair, and Sarah Adler-Flindt (DE) as vice-chair of the 3Rs Working Party. 14.3.5. Election of CNSWP Vice-chair Action: For election Nomination(s) received The elections were postponed and the deadline of the call for Central Nervous System Working Party vice-chair was extended. 14.3.6. Election of VWP Vice-chair Action: For election Nomination(s) received The elections were postponed and the deadline of the call for Vaccines Working Party vice- chair was extended. 14.3.7. CVSWP Response to the CHMP request on indication wording Discussion on the indication wording Action: For discussion The CHMP discussed the indication wording. 14.3.8. Nomination of CHMP representatives to the PCWP and HCPWP Nomination of a CHMP representative (and alternate) for each working party for the mandate June 2025 to May 2028. Nomination(s) received Action: For endorsement The CHMP nominated Ewa Bałkowiec-Iskra (PL) as representative and Fatima Ventura (PT) as alternate to the PCWP. The CHMP nominated Kristina Nadrah (SI) as representative and Ingrid Wang (NO) as alternate to the HCPWP. 14.3.9. ICH Q3E draft Guideline on Extractables and Leachables - Step 2b The ICH Q3E Expert Working Group has completed a draft guideline covering the assessment and control of extractables and leachables (E&L). The document is presented

Page 58/67 for adoption for a 4-month public consultation. The CHMP noted the update of the ICH Q3E draft Guideline on Extractables and leachables - Step 2b, which will be adopted at a later stage. [Post-meeting note: The document was adopted via written procedure on the 05th of August.] 14.4. Cooperation within the EU regulatory network No items 14.5. Cooperation with International Regulators No items 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 15. Any other business 15.1. AOB topic 15.1.1. GIREX rules Analysis of requests for clock-stop extensions and feedback from GIREX. Action: For discussion The CHMP discussed the requests for clock-stop extensions and feedback from GIREX.

Page 59/67 16. List of participants List of participants including any restrictions with respect to involvement of members/alternates/experts following evaluation of declared interests for the 21-24 July 2025 CHMP meeting, which was held in- person. An asterisk (*) after the role, in the second column, signals that the member/alternate attended remotely. Additional experts participated in the meeting, either in person or remotely. Name Role Member State or following for which Bruno Sepodes Chair Portugal meeting Daniela Philadelphy Member Austria Christian Gartner Alternate Austria Christophe Focke Member Belgium meeting Karin Janssen van Doorn Alternate Belgium Lyubina Racheva Todorova Member Bulgaria meeting Gergana Lazarova Bulgaria meeting Margareta Bego Member Croatia Selma Arapovic Dzakula Alternate Croatia Emilia Mavrokordatou Member Cyprus Katerina Savvidou Cyprus Tomas Radimersky Member Czechia Petr Vrbata Czechia Thalia Marie Estrup Blicher Member Denmark Boje Kvorning Pires Ehmsen Alternate Denmark Alar Irs Member Estonia meeting Edward Laane Alternate Estonia meeting Outi Mäki-Ikola Member (Vice- Chair) Finland meeting Johanna Lähteenvuo Alternate Finland Alexandre Moreau Member France Jean-Michel Race Alternate France meeting Janet Koenig Member Germany Martin Mengel Germany Aris Angelis Member Greece 4.3.1. Abrysvo - Respiratory syncytial virus vaccine (bivalent,

Page 60/67 Name Role Member State or following for which recombinant) - EMA/X/0000258051; 5.1.3. BESPONSA - Inotuzumab ozogamicin - EMA/VR/0000257310; 10.1.1. Oxbryta - Voxelotor - EMEA/H/A- 20/1538/C/004869/0014; 5.1.13. Keytruda – Pembrolizumab - EMA/VR/0000245108; 5.1.17. Noxafil – Posaconazole - EMA/VR/0000263360; 5.1.18. Recarbrio - Imipenem / Cilastatin / Relebactam - EMA/VR/0000265089; 3.2.1. - Clesrovimab - EMEA/H/C/00649; 5.1.24. TEZSPIRE – Tezepelumab - EMA/VR/0000245013; 9.1.3. WS2780 Riltrava Aerosphere- EMEA/H/C/005311/WS2780/0017 Trixeo Aerosphere- EMEA/H/C/004983/WS2780/0024; 9.1.4. Fluenz Tetra - Influenza vaccine (live attenuated, nasal) – EMEA/H/C/002617 Anastasia Mountaki Alternate Greece Robert Porszasz Member* Hungary meeting Beata Maria Jakline Ullrich Alternate Hungary Hrefna Gudmundsdottir Member Iceland Hjalti Kristinsson Alternate Iceland Jayne Crowe Member Ireland Finbarr Leacy Alternate Ireland Paolo Gasparini Member Italy meeting Maria Grazia Evandri Italy

Page 61/67 Name Role Member State or following for which Elita Poplavska Member Latvia meeting Vilma Petrikaite Member Lithuania meeting Larisa Gorobets Alternate Lithuania Martine Trauffler Member Luxembourg Alexandra Branchu Luxembourg John Joseph Borg Member Malta meeting Peter Mol Member meeting Patrick Vrijlandt Alternate meeting Ingrid Wang Member Norway Eva Skovlund Alternate Norway meeting Ewa Balkowiec Iskra Member Poland meeting Fatima Ventura Member Portugal meeting Paulo Paixão Alternate Portugal meeting Simona Badoi Member* Romania Dana Gabriela Marin Romania Frantisek Drafi Member Slovakia meeting Jana Klimasová Alternate Slovakia meeting Kristina Nadrah Member Slovenia meeting Carolina Prieto Fernandez Member* Spain Antonio Gomez-Outes Alternate Spain Kristina Dunder Member Sweden Filip Josephson Alternate Sweden Bruno Delafont Co-opted member France Carla Torre Co-opted member Portugal meeting Jan Mueller-Berghaus Co-opted member* Germany Blanka Hirschlerova Co-opted member Czechia

Page 62/67 Name Role Member State or following for which Sol Ruiz Co-opted member Spain Jana Schweigertová Expert Slovakia Nikola Gejgušová Expert Slovakia Mário Miguel Coelho da Silva Rosa Expert Portugal meeting Ana Catarina Fonseca Expert Portugal meeting Uta Buckpesch-Heberer Expert Germany Ger van Zandbergen Expert Germany meeting Lukas Malte Aguirre Dávila Expert Germany meeting Julia Katharina Maier Expert Germany Anja Schmidt Expert Germany Marion Haberkamp Expert Germany Christine Greiner Expert Germany Georgios Aislaitner Expert Germany Jeanette McCallion Expert Ireland Liam McDonough Expert Ireland Sandra Bright Expert Ireland Dhruva Teja Thurlapati Expert Ireland Gabriele Maurer Expert Germany Tihana Slezak Expert Croatia Hrvoje Rimac Expert Croatia 4.3.5. Lojuxta – Lomitapide - EMA/X/0000258068; 5.1.12. Invokana - Canagliflozin - EMEA/H/C/002649/II/0069 Lidija Prka Expert Croatia Višnja Drinovac Vlah Expert Croatia Melanie Ramberger Expert Austria Thomas Lang Expert Austria Bojana Divkovic Expert Austria Lisa Nika Expert Austria Sabrina Jenull Expert Austria Michael Jirout Expert Austria Silke Dorner Expert Austria Elina Rantala Expert Finland Paolo Foggi Expert Italy Pierre Demolis Expert Iceland Anna Vikerfors Expert Sweden Elisabeth Wischnitzki Expert Austria André Elferink Expert Silvijus Abramavicius Expert Lithuania Hilke Zander Expert Germany Cristina Migali Expert Italy Jutta Dedorath Expert Germany Bruna Dekic Expert Germany

Page 63/67 Name Role Member State or following for which Ulrike Hermes Expert Germany Susanna Hausmann Expert Germany Julian Paesler Expert Germany Peter van de Ven Expert meeting Thea Trijntje Klamer Expert Ingrid Schellens Expert Melissa van Tok Expert 3.2.1. - Clesrovimab - EMEA/H/C/006497; 5.1.13. Keytruda – Pembrolizumab - EMA/VR/0000245108; 5.1.17. Noxafil – Posaconazole - EMA/VR/0000263360; 5.1.18. Recarbrio - Imipenem / Cilastatin / Relebactam - EMA/VR/00002650Robert Pollmann Expert Germany Susanne Müller-Egert Expert Germany Christian Baarlink Expert Germany Jörg Engelbergs Expert Germany Simin Oveisi Expert France meeting Céline Jumeau Expert France Muriel Uzzan Expert France Ramzi Mraidi Expert France meeting Violette Dirix Expert Belgium meeting Ingrid Bourges Expert Belgium meeting Jean-Michel Dogné Expert Belgium meeting Jean-Noël Talbot Expert France meeting Violaine Closson Carella Expert France Agnes Mambole Dema Expert France Ilona G. Reischl Expert Austria meeting Anna Mari Lone Expert Norway meeting

Page 64/67 Name Role Member State or following for which Ole Henrik Myrdal Expert Norway Rune Kjeken Expert Norway Sarah Lang Expert Germany Sarah Adler-Flint Expert Germany Ana Rita Lemos Expert Portugal meeting Sabine Mayrhofer Expert Germany Christoph Furtmann Expert Germany meeting Johanna de Groot Expert Hemme Jacob Hijma Expert meeting Susanna Uiterwaal Expert Illiana Meurs Expert Viktoriia Starokozhko Expert meeting Carlijn Litjens Expert meeting A representative from the European Commission attended the meeting Meeting run with the help of EMA staff. Experts were evaluated against the agenda topics or activities they participated in.

Page 65/67 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.

Page 66/67 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, 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.

Page 67/67 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 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/

Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands An agency of the European Union 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 © European Medicines Agency, 2025. Reproduction is authorised provided the source is acknowledged. 24 July 2025 Annex to 21-24 July 2025 CHMP Minutes 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 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 ...................................... 3 B.2.1. Renewals of Marketing Authorisations requiring 2nd Renewal ................................ 3 B.2.2. Renewals of Marketing Authorisations for unlimited validity ................................... 3 B.2.3. Renewals of Conditional Marketing Authorisations ................................................ 3 B.3. POST-AUTHORISATION PHARMACOVIGILANCE OUTCOMES...................................... 3 B.5. TYPE II VARIATION, WORKSHARING PROCEDURE OUTCOMES ................................. 4 B.5.1. CHMP assessed procedures scope: Pharmaceutical aspects ................................... 4 B.5.2. CHMP assessed procedures scope: Non-Clinical and Clinical aspects ....................... 5 B.5.3. CHMP-PRAC assessed procedures ...................................................................... 6 B.5.4. PRAC assessed procedures ................................................................................ 8 B.5.5. CHMP-CAT assessed procedures ........................................................................ 9 B.5.6. CHMP-PRAC-CAT assessed procedures ............................................................... 9 B.5.7. PRAC assessed ATMP procedures ....................................................................... 9 B.5.8. Unclassified procedures and worksharing procedures of type I variations ................ 9 B.5.9. Information on withdrawn type II variation / WS procedure .................................. 9 B.5.10. Information on type II variation / WS procedure with revised timetable ................ 9 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) ........................................................................................... 9 E. Annex E - EMA CERTIFICATION OF PLASMA MASTER FILES ................... 9 E.1. PMF Certification Dossiers .................................................................................... 9 E.2. Time Tables – starting & ongoing procedures: For information ................................. 9

Page 2/9 F. ANNEX F - Decision of the Granting of a Fee Reduction/Fee Waiver ...... 9 G. ANNEX G ................................................................................................ 9 G.1. Final Scientific Advice (Reports and Scientific Advice letters): .................................. 9 G.2. PRIME ............................................................................................................... 9

Page 3/9 A. PRE-SUBMISSION ISSUES A.1. ELIGIBILITY REQUESTS Report on Eligibility to Centralised Procedure for July 2025: For adoption Adopted A.2. Appointment of Rapporteur / Co-Rapporteur Full Applications Final Outcome of Rapporteurship allocation for July 2025: For adoption Adopted B. POST-AUTHORISATION PROCEDURES OUTCOMES B.1. Annual re-assessment outcomes B.1.1. Annual reassessment for products authorised under exceptional circumstances Livmarli - Maralixibat - EMEA/H/C/005857/S/0019, Orphan Mirum Pharmaceuticals International B.V., Rapporteur: Janet Koenig, PRAC Rapporteur: Adam Przybylkowski on 25.04.2025. Positive Opinion adopted by consensus together with the CHMP assessment report and translation timetable. The Marketing Authorisation remains under exceptional circumstances B.2. RENEWALS OF MARKETING AUTHORISATIONS OUTCOMES B.2.1. Renewals of Marketing Authorisations requiring 2nd Renewal B.2.2. Renewals of Marketing Authorisations for unlimited validity B.2.3. Renewals of Conditional Marketing Authorisations B.3. POST-AUTHORISATION PHARMACOVIGILANCE OUTCOMES Signal detection PRAC recommendations on signals adopted at the PRAC meeting held on 07-10 July 2025 PRAC:

Page 4/9 Signal of Progressive multifocal leukoencephalopathy Varicella Vaccine (live); Measles, Mumps, Rubella and Varicella Vaccine (Live) - PROQUAD (CAP & NAP) Rapporteur: Jan Mueller-Berghaus, Co- Rapporteur: Paolo Gasparini, PRAC Rapporteur: Gabriele Maurer PRAC recommendation on a variation The CHMP adopted the PRAC recommendation. Signal of progressive multifocal leukoencephalopathy Ciltacabtagene autoleucel, idecabtagene vicleucel, tisagenlecleucel – CARVYKTI, Abecma, Kymriah (CAP) Rapporteur: multiple, Co-Rapporteur: multiple, PRAC Rapporteur: multiple PRAC recommendation on a variation The CHMP adopted the PRAC recommendation. PSUR procedures for which PRAC adopted a recommendation for variation of the terms of the MA at its July 2025 meeting: 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 Idacio - Adalimumab - EMEA/H/C/004475/II/0024/G Fresenius Kabi Deutschland GmbH, Rapporteur: Peter Mol, PRAC Rapporteur: Karin Bolin on 24.07.2025, 27.03.2025. Pombiliti - Cipaglucosidase alfa - EMEA/H/C/005703/II/0019 Amicus Therapeutics Europe Limited, Rapporteur: Patrick Vrijlandt Opinion adopted on 03.07.2025. on 25.04.2025. 03.07.2025. POTELIGEO - Mogamulizumab - EMEA/H/C/004232/II/0028/G, Orphan

Page 5/9 Kyowa Kirin Holdings B.V., Rapporteur: Peter Mol Opinion adopted on 26.06.2025. on 27.03.2025. 26.06.2025. WS2780 Riltrava Aerosphere- EMEA/H/C/005311/WS2780/0017 Trixeo Aerosphere- EMEA/H/C/004983/WS2780/0024 AstraZeneca AB, Lead Rapporteur: Finbarr Leacy, Lead PRAC Rapporteur: Jan Neuhauser Opinion adopted on 24.07.2025. on 22.05.2025, 30.01.2025. 24.07.2025. See 9.1 B.5.2. CHMP assessed procedures scope: Non-Clinical and Clinical aspects Paxlovid - Nirmatrelvir / Ritonavir - EMEA/H/C/005973/II/0059/G Pfizer Europe MA EEIG, Rapporteur: Jean-Michel Race, “A grouped application consisting of: C.I.4: Update of section 4.5 of the SmPC in order to add drug-drug interaction information with albendazole based on the post-marketing data and literature and to update information on drug-drug interactions with methadone and ethinyl estradiol based on the literature; the Package Leaflet is updated accordingly. C.I.4: Update of section 4.5 of the SmPC in order to update information on drug-drug interactions with calcium channel antagonists based on the cumulative safety data and literature.” on 15.05.2025, 23.01.2025. WS2818 PecFent- EMEA/H/C/001164/WS2818/0062 Gruenenthal GmbH, Lead Rapporteur: Janet Koenig, “Update of section 4.5 of the SmPC in order to add drug-drug interaction information between opioids and anticholinergics; the Package Leaflet is updated accordingly.” on 15.05.2025, 13.03.2025. Negative Opinion adopted by consensus on 24.07.2025. Dengue Tetravalent Vaccine (Live, Attenuated) Takeda-

Page 6/9 EMEA/H/W/005362/WS2809/0021 Qdenga- EMEA/H/C/005155/WS2809/0022 Takeda GmbH, Lead Rapporteur: Sol Ruiz, “Update of section 4.8 of the SmPC in order to add eye pain to the list of adverse drug reactions (ADRs) with frequency uncommon based on post-marketing data; the Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet and to introduce editorial changes to the PI.” Opinion adopted on 17.07.2025. on 20.03.2025. 17.07.2025. B.5.3. CHMP-PRAC assessed procedures Sunosi - Solriamfetol - EMEA/H/C/004893/II/0026 Atnahs Pharma Netherlands B.V., Rapporteur: Janet Koenig, PRAC Rapporteur: Julia Pallos, “Update of sections 4.6 and 5.2 of the SmPC in order to update information on lactation and breast-feeding based on results from the post- marketing lactation study JZP110-401 listed as a category 3 study in the RMP. This was a Phase 4, open-label, single-dose study to evaluate the PK of solriamfetol in the breast milk and plasma of healthy postpartum women following oral administration of a 150 mg solriamfetol tablet. The Package Leaflet is updated accordingly. The RMP version 1.3 has also been submitted.” on 08.05.2025. ZTALMY - Ganaxolone - EMEA/H/C/005825/II/0004/G, Orphan Immedica Pharma AB, Rapporteur: Peter Mol, PRAC Rapporteur: Adam Przybylkowski, “A grouped application comprised of 8 Type II variations as follows: 1 Type II (C.I.4): Update of section 5.2 of the SmPC in order to update ganaxolone metabolite pattern at steady state based on re-analysis of 1042-TQT-1001 listed as a category 3 study in the RMP to evaluate the ganaxolone steady- state metabolite.

Page 7/9 7 Type II (C.I.13): Submission of the final non- clinical study reports for the in vitro DDI potential and in vivo PK of the metabolite M17 listed as category 3 studies in the RMP. The RMP version 1.2 has also been submitted. In addition, the MAH took the opportunity to introduce updates to the PI that reflect clarifications and typographical corrections, including to sections 4.2 and 4.4 of the SmPC.” on 24.07.2025, 27.03.2025, 25.07.2024, 11.04.2024. ZTALMY - Ganaxolone - EMEA/H/C/005825/II/0015/G, Orphan Immedica Pharma AB, Rapporteur: Peter Mol, PRAC Rapporteur: Adam Przybylkowski, “A grouped application consisting of five Type II variations, as follows: C.I.13: Submission of the final report from non- clinical study 1022-9241 listed as a category 3 study in the RMP. This is a 26-Week Toxicity Study of Ganaxolone Metabolite, M2, by Oral Gavage in the Sprague-Dawley rat with a 2- Week Recovery Period. The RMP version 3 has also been submitted. C.I.13: Submission of the final report from non- clinical study 20447815 listed as a category 3 study in the RMP. This is a An Oral (Gavage) Study of the Effects of M2 (Ganaxolone Metabolite) Administration on Embryo/Fetal Development in CD (Sprague Dawley) IGS Rat. The RMP version 3 has also been submitted. C.I.13: Submission of the final report from Weight of Evidence (WoE) assessment to evaluate the need for a 2-year carcinogenicity study in rats with GNX, listed as a category 3 study in the RMP. C.I.13: Submission of the final report from WoE assessment to evaluate the need for a 2-year carcinogenicity study in rats with M2, listed as a category 3 study in the RMP. C.I.13: Submission of the final report from WoE assessment to evaluate the need for a juvenile toxicity study with M2, listed as a category 3

Page 8/9 study in the RMP. ” on 10.07.2025, 13.03.2025. B.5.4. PRAC assessed procedures PRAC Led Enbrel - Etanercept - EMEA/H/C/000262/II/0255 Pfizer Europe MA EEIG, PRAC Rapporteur: Monica Martinez Redondo, PRAC-CHMP liaison: Antonio Gomez-Outes, “Update of the RMP version 7.9 to remove the important risks of “Aplastic Anaemia and Pancytopenia”, “Congestive Heart Failure in Adult Subjects” and “Acute Ischaemic Cardiovascular Events in Adults Subjects” and the missing information “Immunogenicity Profile and Related Clinical Outcomes of Etanercept Manufactured using the revised process in a Real-life Post-marketing Setting’’ from the list of SCs. In addition, the MAH took the opportunity to introduce minor editorial and formatting changes to the PI as well as to update the list of local representatives in the Package Leaflet and align the PI with the QRD version 10.4.” on 10.04.2025, 16.01.2025. PRAC Led Mimpara - Cinacalcet - EMEA/H/C/000570/II/0076 Amgen Europe B.V., PRAC Rapporteur: Mari Thorn, PRAC-CHMP liaison: Kristina Dunder, “Submission of the final report from study 20180204 listed as a category 3 study in the RMP. This is a non-interventional observational registry study to evaluate the use and safety of cinacalcet among paediatric patients with secondary hyperparathyroidism (HPT).” on 13.03.2025.

Page 9/9 B.5.5. CHMP-CAT assessed procedures 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 B.5.9. Information on withdrawn type II variation / WS procedure B.5.10. Information on type II variation / WS procedure with revised timetable 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. PMF Certification Dossiers E.2. Time Tables – 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. G.2. PRIME Some information related to PRIME cannot be released at the present time as these contain commercially confidential information.