CHMP Minutes for September 2022 - Oncology

The meeting minutes from the European Medicine’s Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) 12-15 September 2022 meeting were released on the 3rd of November 2022. Items of interest listed below:

Oral Explanations

Re-examination procedure oral explanations

• Tuznue (trastuzumab) / Hervelous (trastuzumab) - Prestige Biopharma Belgium
  • treatment of metastatic and early breast cancer and metastatic gastric cancer (MGC)
  • An oral explanation was held on 13 September 2022. The presentation by the applicant focused on the quality data in support of the application.

Initial applications

Initial applications; Opinions

• Sorafenib Accord (sorafenib) - Accord Healthcare S.L.U.
  • treatment of hepatocellular carcinoma and renal cell carcinoma.
• The Committee adopted a positive opinion recommending the granting of a marketing authorisation by consensus together with the CHMP assessment report and translation timetable.

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

• Pemetrexed - Pfizer Europe MA EEIG
  • treatment of malignant pleural mesothelioma and non-small cell lung cancer.
  • The Committee was reminded of the status of this application and its remaining outstanding issues.
  • The Committee adopted a 2nd list of outstanding issues with a specific timetable.

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

• Niraparib / abiraterone acetate
  • treatment of adult patients with prostate cancer.
  • The Committee adopted the CHMP recommendation and scientific discussion together with the list of questions.
• Adagrasib
  • treatment of patients with advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation.
  • The Committee adopted the CHMP recommendation and scientific discussion together with the list of questions.

Re-examination of initial application procedures

• Hervelous (trastuzumab) - Prestige Biopharma Belgium
  • treatment of metastatic and early breast cancer and metastatic gastric cancer (MGC).
  • The MAH withdrew the marketing authorisation application.
• Tuznue (trastuzumab) - Prestige Biopharma Belgium
  • treatment of metastatic and early breast cancer and metastatic gastric cancer (MGC).
  • The MAH withdrew the marketing authorisation application.

Extension of marketing authorisation

Update on on-going extension application

• Calquence (acalabrutinib) - AstraZeneca AB
  • a cancer medicine used to treat adults with chronic lymphocytic leukaemia (CLL), a blood cancer affecting B cells (a type of white blood cell).
  • Scope: Extension application to introduce a new pharmaceutical form, film-coated tablet. A.6 - To change the ATC Code of acalabrutinib from L01XE51 to L01EL02
  • The Committee noted the status of this application.

Type II variations - variation of therapeutic indication procedure

Type II variations - variation of therapeutic indication procedure; Opinions or Requests for supplementary information

• Breyanzi (lisocabtagene maraleucel / lisocabtagene maraleucel – ATMP) - Bristol-Myers Squibb Pharma EEIG
  • treatment of diffuse large B-cell lymphoma (DLBCL); primary mediastinal large B-cell lymphoma (PMBCL); follicular lymphoma grade 3B (FL3B).
  • Scope: Extension of indication to include treatment of adult patients with Second-line (2L) Transplant Intended (TI) Large B-Cell Lymphoma (LBCL) for Breyanzi, based on interim analyses from pivotal study JCAR017-BCM-003; this is a global randomized multicentre Phase III Trial to compare the efficacy and safety of JCAR017 to standard of care in adult subjects with high-risk, transplant-eligible relapsed or refractory aggressive B-cell Non-Hodgkin Lymphomas (TRANSFORM); 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 2.0 of the RMP has also been submitted.
  • The CHMP was updated on discussions at the CAT, concerning clinical aspects and endorsed a request for supplementary information with a specific timetable, as adopted by CAT.
• Brukinsa (zanubrutinib) - BeiGene Ireland Ltd
  • treating adults with Waldenström’s macroglobulinaemia, the most common type of lymphoplasmacytic lymphoma.
  • Scope: Extension of indication to include treatment of adult patients with marginal zone lymphoma (MZL) who have received at least one-prior anti-CD20-based therapy, based on data from 88 patients with R/R MZL from 2 ongoing pivotal studies; study BGB-3111-214: A Phase 2, open-label, single-arm study designed to evaluate the safety and efficacy of zanubrutinib in patients with R/R MZL, and study BGB-3111-AU-003: A first-in-human, Phase 1/2, dose-escalation and selection, PK/pharmacodynamic, safety, and efficacy study in adult patients with R/R or treatment-naive B-cell malignancies. As a consequence, sections 4.1, 4.2, 4.5, 4.8 and 5.1 of the SmPC are updated and the Package Leaflet is updated in accordance. Version 1.1 of the RMP has also been submitted. In addition, the MAH is requesting one additional year of market protection. Request for 1 year of market protection for a new indication.
  • The Committee adopted a positive opinion by consensus together with the CHMP Assessment Report and translation timetable.
• Enhertu (trastuzumab deruxtecan) - Daiichi Sankyo Europe GmbH
  • a medicine used to treat breast cancer that is metastatic (has spread to other parts of the body) or cannot be removed by surgery.
  • Scope: Extension of indication to include treatment of unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. Patients with hormone receptor positive (HR+) breast cancer must additionally have received or be ineligible for endocrine therapy; for Enhertu, based on final results from study DS8201-A-U303 (DESTINY-Breast04). This is a Phase III, multicentre, randomised, open-label, active-controlled trial of Trastuzumab Deruxtecan (T-DXd), an Anti-HER2-antibody Drug Conjugate (ADC), versus treatment of physician’s choice for HER2-low, unresectable and/or metastatic breast cancer subjects. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 1.4 of the RMP has also been submitted. In addition, the Marketing authorisation holder (MAH) took the opportunity to update section 4.4 of the SmPC to update the dosing recommendation for corticosteroid treatment (e.g. prednisolone) with a daily dose.
  • The Committee discussed the issues identified in this application, concerning the wording of the indication and adopted a request for supplementary information with a specific timetable.
• Gavreto (pralsetinib) - Roche Registration GmbH
  • a cancer medicine for treating adults with advanced non-small cell lung cancer caused by changes in a gene called RET (known as RET fusion-positive NSCLC) and who have not been treated with a RET inhibitor.
  • Scope: Extension of indication to include monotherapy treatment of adult and paediatric patients 12 years of age and older with locally advanced or metastatic RET-mutant medullary thyroid cancer for Gavreto; based on the efficacy and safety data obtained from the pivotal study BO42863 (ARROW). As a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1, 5.2 and 5.3 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 1.1 of the RMP has also been submitted. Furthermore, some minor changes to the PI have been implemented in line with the latest Anticancer Guidelines Recommendations. Extension of indication to include monotherapy treatment of adult and paediatric patients 12 years of age and older with locally advanced or metastatic RET fusion-positive thyroid cancer for Gavreto; based on the efficacy and safety data obtained from the pivotal study BO42863 (ARROW). As a consequence, sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1, 5.2 and 5.3 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 1.1 of the RMP has also been submitted. Request for 1 year of market protection for a new indication.
  • The Committee discussed the issues identified in this application, concerning clinical aspects and adopted a 3rd request for supplementary information with a specific timetable.
• Nubeqa (darolutamide) - Bayer AG
  • medicine used to treat men with prostate cancer
  • Scope: Extension of indication to include treatment of adult men with metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel, based on final results from study 17777 (ARASENS); this is a randomized, double-blind, placebo-controlled Phase 3 study designed to demonstrate the superiority of darolutamide in combination with docetaxel over placebo in combination with docetaxel in OS in patients with mHSPC. As a consequence, sections 4.1, 4.2, 4.5, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 2.1 of the RMP has also been submitted. As part of the application, the MAH is also requesting one additional year of market protection. Request for 1 year of market protection for a new indication.
  • The Committee discussed the issues identified in this application, concerning the request for 1 year of market protection and adopted a 2nd request for supplementary information with a specific timetable.
• Xalkori (crizotinib) - Pfizer Europe MA EEIG
  • a cancer medicine used on its own to treat adults with a type of lung cancer called non-small cell lung cancer (NSCLC)
  • Scope: Extension of indication to include treatment of paediatric patients (age ≥ 6 to < 18 years) with relapsed or refractory systemic anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) and with unresectable, recurrent, or refractory ALK-positive inflammatory myofibroblastic tumour (IMT) for Xalkori based on the results from studies ADVL0912 and A8081013.
  • The Committee adopted a positive opinion by majority (30 positive votes out of 31 votes) together with the CHMP assessment report and translation timetable. The divergent position (Paula Boudewina van Hennik) was appended to the opinion.

Post-authorisation issues

Post-authorisation issues

• Rubraca (rucaparib) - Clovis Oncology Ireland Limited
  • Scope: Update of sections 4.4 and 4.8 of the SmPC based on safety data from study CO-338-043 (ARIEL 4); this is a phase 3, multicentre, open-label, randomised study evaluating the efficacy and safety of rucaparib versus chemotherapy for treatment of relapsed ovarian cancer listed as a specific obligation in the Annex II; the Package Leaflet is updated accordingly. The RMP version 6.2 is acceptable. Update of Annex II to remove the specific obligation. The SmPC and Package leaflet are amended accordingly to reflect the conversion from a conditional marketing authorisation to a marketing authorisation no longer subject to specific obligations as recommended by the CHMP as a result of this variation and further to the removal of the indication for monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum based chemotherapy, and who are unable to tolerate further platinum based chemotherapy (EMEA/H/A-20/1518/C/4272/0033). In addition, the MAH took the opportunity to make minor editorial changes and bring the PI in line with the latest QRD template version 10.2 Rev.1.
  • The Committee adopted a positive opinion by consensus together with the CHMP Assessment Report and translation timetable.
• Caprelsa (vandetanib) - Genzyme Europe BV
  • Scope: Renewal of marketing authorization
  • The Committee adopted a positive opinion by consensus together with the CHMP Assessment Report and translation timetable.
• Caprelsa (vandetanib) - Genzyme Europe BV
  • Scope: C.I.4 Update of section 5.1 of the SmPC in order to update pharmacodynamic information based on interim results from study D4200C00104, listed as a specific obligation in the Annex II. This is an observational study (including a retrospective arm to evaluate the Benefit/Risk of vandetanib (Caprelsa) 300 mg in RET mutation negative and RET mutation positive patients with symptomatic, aggressive, sporadic, unresectable, locally advanced/metastatic thyroid cancer (MTC)), to confirm the efficacy and safety of Caprelsa in RET-negative patients with the aim to fulfil SOB001 and convert Caprelsa from conditional to normal Marketing Authorisation. In addition, the MAH takes to opportunity to rectify the Dutch translation of the Caprelsa Product Information.
  • The Committee adopted a positive opinion by consensus together with the CHMP Assessment Report and translation timetable.
  • Based on the review of the available information, the CHMP was of the opinion that all specific obligations have been fulfilled. Therefore, the CHMP recommended granting of a Marketing Authorisation not subject to specific obligations.
  • The CHMP agreed on the wording of a direct healthcare professional communication (DHPC) together with a communication plan.

 

RENEWALS OF MARKETING AUTHORISATIONS OUTCOMES

Renewals of Marketing Authorisations for unlimited validity

• Fulvestrant Mylan (fulvestrant) - Mylan Pharmaceuticals Limited
  • Request for supplementary information adopted with a specific timetable.
• Herzuma (trastuzumab) - Celltrion Healthcare Hungary Kft.,
  • Positive Opinion adopted by consensus together with the CHMP assessment report and translation timetable.
  • Based on the review of the available information, the CHMP was of the opinion that the renewal of the marketing authorisation can be granted with unlimited validity.

Renewals of Conditional Marketing Authorisations

• Caprelsa (vandetanib) - Genzyme Europe BV
  • Positive Opinion adopted by consensus together with the CHMP assessment report.
  • The CHMP was of the opinion that the renewal for this conditional Marketing Authorisation can be granted.
  • The Marketing Authorisation remains conditional.
• Enhertu (trastuzumab deruxtecan) - Daiichi Sankyo Europe GmbH
  • Positive Opinion adopted by consensus together with the CHMP assessment report.
  • The CHMP was of the opinion that the renewal for this conditional Marketing Authorisation can be granted.
  • The Marketing Authorisation remains conditional.
• Lumykras (sotorasib) - Amgen Europe B.V
  • Positive Opinion adopted by consensus together with the CHMP assessment report.
  • The CHMP was of the opinion that the renewal for this conditional Marketing Authorisation can be granted.
  • The Marketing Authorisation remains conditional.

CHMP assessed procedures scope: Pharmaceutical aspects

• Alecensa (alectinib) - Roche Registration GmbH
  • Request for supplementary information adopted with a specific timetable.
• Kadcyla (trastuzumab emtansine) - Roche Registration GmbH
  • Positive Opinion adopted by consensus on 08.09.2022.
• Phesgo (pertuzumab / trastuzumab) - Roche Registration GmbH
  • Request for supplementary information adopted with a specific timetable.
• Ruxience (rituximab) - Pfizer Europe MA EEIG
  • Positive Opinion adopted by consensus on 01.09.202.
• Spectrila (asparaginase) - medac Gesellschaft fur klinische Spezialpraparate mbH
  • Request for supplementary information adopted with a specific timetable.
• Spectrila (asparaginase) - medac Gesellschaft fur klinische Spezialpraparate mbH
  • Positive Opinion adopted by consensus on 01.09.2022.
• Tecentriq (atezolizumab) - Roche Registration GmbH
  • Positive Opinion adopted by consensus on 01.09.2022.
• Vectibix (panitumumab) - Amgen Europe B.V.
  • Positive Opinion adopted by consensus on 01.09.2022.
• Votrient (pazopanib) - Novartis Europharm Limited
  • Positive Opinion adopted by consensus on 01.09.2022.

CHMP assessed procedures scope: Non-Clinical and Clinical aspects

• Bavencio (avelumab) - Merck Europe B.V.
  • Update of sections 4.2, 5.1 and 5.2 of the SmPC based on final results from study MS100070-0306 following a P46 procedure (EMEA/H/C/004338/P46/009). This is a Phase I, multi-centre, open-label, international study to evaluate the dose, safety and tolerability, antitumor activity, pharmacokinetic and pharmacodynamics of avelumab in paediatric subjects 0 to less than 18 years of age with refractory or relapsed malignant solid tumours (including central nervous system tumours) and lymphoma for which no standard therapy is available or for which the subject is not eligible for the existing therapy. In addition, the MAH took the opportunity to update Annex II section D to be aligned with the EU Educational materials (EM) and the EU Risk Management Plan (RMP). Furthermore, the MAH took the opportunity to implement editorial changes.
  • Positive Opinion adopted by consensus on 15.09.2022.
• CABOMETYX (cabozantinib) - Ipsen Pharma
  • Update of sections 4.4 and 4.8 of the SmPC in order to update special warnings data and information of adverse drug reactions (ADRs) based on results from study XL184-311 (COSMIC-311); study XL184-311 was a Phase 3 international, multicenter, randomized, double-blind, placebo-controlled study of cabozantinib in subjects with radioiodine (RAI)-refractory differentiated thyroid cancer (DTC) who had progressed during or after prior vascular endothelial growth factor receptor (VEGFR)- targeted therapy. In addition, the MAH is taking this opportunity to propose minor updates to the Package Leaflet.
  • Positive Opinion adopted by consensus on 15.09.2022.
• Calquence (acalabrutinib) - AstraZeneca AB
  • Update of section 5.1 of the SmPC in order to update efficacy and safety information based on final results from study ACE-CL-309 (A Phase 3 randomized open-label active-control study investigating Calquence for the treatment of Subjects with relapsed or Refractory Chronic Lymphocytic Leukaemia) listed as a category 3 study in the RMP.
  • Positive Opinion adopted by consensus on 15.09.2022.
• Keytruda (pembrolizumab) - Merck Sharp & Dohme B.V.
  • To update sections 4.2 and 5.2 of the SmPC to include data for patients with moderate hepatic impairment based on KEYNOTE-240 (a double-blind, randomized, Phase 3 study of pembrolizumab in participants with previously systemically treated advanced HCC) and KEYNOTE-224 (a Phase 2 study of pembrolizumab as monotherapy in participants with advanced HCC). The MAH took the opportunity to make some editorial changes.
  • Positive Opinion adopted by consensus on 15.09.2022
• Lumykras (sotorasib) - Amgen Europe B.V.
  • Update of section 4.2 of the SmPC based on results from the enteral feeding tube in vitro study (RPT-574024), undertaken to assess the feasibility of administration of sotorasib 120 mg film-coated tablets through an enteral feeding tube. The Package Leaflet was updated accordingly.
  • Positive Opinion adopted by consensus on15.09.2022.
• Lumykras (sotorasib) - Amgen Europe B.V.
  • Update of section 4.5 of the SmPC based on the results of study 2020042, a phase 1 clinical drug interaction study undertaken to assess the effect of concomitant sotorasib administration on the systemic exposure of breast cancer resistance protein (BCRP) transporter substrates. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to implement minor editorial changes in the SmPC and Package Leaflet.
  • Positive Opinion adopted by consensus on 15.09.2022.
• Lysodren (mitotane) - HRA Pharma Rare Diseases
  • Update of sections 4.4 and 4.8 of the SmPC new safety information regarding skin reactions (including rash, pruritus, urticaria…) and estrogenic effects in children based on post-marketing safety report and literature. The Package Leaflet is updated accordingly.
  • Request for supplementary information adopted with a specific timetable.
• Revlimid (lenalidomide) - Bristol-Myers Squibb Pharma EEIG
  • Update of section 4.2 of the SmPC to update the dosage for patients with impaired renal function (severe renal impairment and end stage renal disease) for the follicular lymphoma (FL) indication based on additional PK analysis. In addition, the MAH proposed to update the existing warning in section 4.4 of the SmPC to highlight that male patients should not donate semen or sperm during treatment and for at least seven days after the end of treatment in order to align with the Revlimid Annex IID requirements for the patient educational brochures and to align with similar wording in the Imnovid (pomaldiomide) and Thalidomide BMS (thalidomide) SmPCs. The Package Leaflet is updated accordingly.
  • Request for Supplementary Information adopted on 22.04.2022.
• Rozlytrek (entrectinib) - Roche Registration GmbH
  • Submission of the final integrated analysis report for cardiac risks, listed as a category 3 study in the RMP, in order to fulfil MEA/003. This is an integrated safety analysis report to assess cardiac risks based on GO40782 [STARTRK-2], CO40778 [STARTRKNG], and BO41932 [TAPISTRY] studies (PAESs).
  • Positive Opinion adopted by consensus on 08.09.2022.
• Venclyxto (venetoclax) - AbbVie Deutschland GmbH & Co. KG
  • Update of section 5.1 of the SmPC in order to update data supporting the efficacy of the combined regimen of obinutuzumab and venetoclax (VEN+G; also known as GDC-0199 or ABT-199) versus obinutuzumab plus chlorambucil (GClb) in previously untreated CLL patients based on final results from study BO25323/CLL14; this is a prospective, open-label, multicenter randomized phase 3 trial to compare the efficacy and safety of a combined regimen of obinutuzumab and venetoclax (GDC-0199/ABT-199) versus obinutuzumab and chlorambucil in previously untreated patients with CLL and coexisting medical conditions. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI.
  • Request for supplementary information adopted with a specific timetable.
• Zercepac (trastuzumab) - Accord Healthcare S.L.U.
  • Submission of the final report from study HLX02-BC01 in order to fulfil REC/006. This is a double-blind, randomised, parallel-controlled, multicentre, international, phase 3 study to compare the efficacy, safety, and immunogenicity of HLX02 versus EU-sourced Herceptin in combination with docetaxel.
  • Request for supplementary information adopted with a specific timetable.
• OPDIVO; Yervoy - Bristol-Myers Squibb Pharma EEIG
  • To update sections 4.8 and 5.1 of the SmPC to include 7.5 years of minimum follow-up for all subjects based on addendum 04 Clinical Study Report for study CA209067; this is a phase 3 randomized, double-blind study of nivolumab monotherapyor nivolumab in combination with ipilimumab versus ipilimumab monotherapy in subjects with previously untreated, unresectable melanoma. The MAH has taken the opportunity to introduce minor editorial revisions in the SmPC.
  • Positive Opinion adopted by consensus on 01.09.2022
• Kisplyx; Lenvima - Eisai GmbH
  • To update of SmPC sections 4.2 and 6.6 to include the option of administering the capsules as a suspension, including instructions for the administration and preparation of the suspension. The MAH also took the opportunity to include some editorial changes to the SmPC.
  • Request for supplementary information adopted with a specific timetable.

CHMP-PRAC assessed procedures

• Caprelsa (vandetanib) - Genzyme Europe BV
  • I.4 Update of section 5.1 of the SmPC in order to update pharmacodynamic information based on interim results from study D4200C00104, listed as a specific obligation in the Annex II. This is an observational study (including a retrospective arm to evaluate the Benefit/Risk of vandetanib (Caprelsa) 300 mg in RET mutation negative and RET mutation positive patients with symptomatic, aggressive, sporadic, unresectable, locally advanced/metastatic thyroid cancer (MTC)), to confirm the efficacy and safety of Caprelsa in RET-negative patients with the aim to fulfil SOB001 and convert Caprelsa from conditional to normal Marketing Authorisation. In addition, the MAH takes to opportunity to rectify the Dutch translation of the Caprelsa Product Information.
  • Positive Opinion adopted by consensus on 15.09.2022.
• Lorviqua (lorlatinib) - Pfizer Europe MA EEIG
  • Submission of an updated RMP version 5.0 to revise plans for conduct of hepatic impairment studies. The RMP is updated to reflect the hepatic impairment study B7461009 “A Phase 1 Study to Evaluate the Effect of Hepatic Impairment on the Pharmacokinetics and Safety of Lorlatinib in Advanced Cancer Patients” termination and to include new hepatic impairment study B7461040 “A Phase 1, Open-label, Single-dose,Parallel-group Study to Evaluate The Plasma Pharmacokinetics and Safety of Lorlatinib in Participants with Moderate and Severe Hepatic Impairment Relative to Participants with Normal Hepatic Function.
  • Positive Opinion adopted by consensus on 15.09.2022.
• Rubraca (rucaparib) - Clovis Oncology Ireland Limited
  • Update of sections 4.4 and 4.8 of the SmPC based on safety data from study CO-338-043 (ARIEL 4); this is a phase 3, multicentre, open-label, randomised study evaluating the efficacy and safety of rucaparib versus chemotherapy for treatment of relapsed ovarian cancer listed as a specific obligation in the Annex II; the Package Leaflet is updated accordingly. The RMP version 6.2 is acceptable. Update of Annex II to remove the specific obligation. The SmPC and Package leaflet are amended accordingly to reflect the conversion from a conditional marketing authorisation to a marketing authorisation no longer subject to specific obligations as recommended by the CHMP as a result of this variation and further to the removal of the indication for monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum based chemotherapy, and who are unable to tolerate further platinum based chemotherapy (EMEA/H/A-20/1518/C/4272/0033). In addition,the MAH took the opportunity to make minor editorial changes and bring the PI in line with the latest QRD template version 10.2 Rev.1.
  • Positive Opinion adopted by consensus on 15.09.2022.
• OPDIVO; Yervoy - Bristol-Myers Squibb Pharma EEIG
  • Update of section 4.8 of the SmPC in alignment with the recommendations made by the CHMP to revise the pooling approach used to describe irARs and tabulated summaries of ADRs following II/0096. Individual study data included within this application has been previously reviewed by the CHMP. The updated Opdivo RMP version 29.0 and Yervoy RMP version 37.0 have also been submitted. The MAH took the opportunity to introduce editorial changes. The Package Leaflet was updated accordingly.
  • Request for supplementary information adopted with a specific timetable.
• Rixathon; Riximyo - Sandoz GmbH
  • Update of section 4.1 of the SmPC in order to include the rapid infusion regimen (90 minutes) for second and subsequent infusions in the label for patients with non-Hodgkin’s lymphoma (NHL) or chronic lymphocytic leukaemia (CLL) based on non-interventional PASS CGP2013ES01R and scientific literature. The RMP version 7.0 has also been submitted.
  • Request for supplementary information adopted with a specific timetable.

PRAC assessed procedures

• Cotellic (cobimetinib) - Roche Registration GmbH
  • Update of sections 4.4 and 5.1 of the SmPC in order to update information based on final results from study ML39302 listed as a category 3 study in the RMP in order to fulfil MEA/003.5; this is a non-interventional PASS study to investigate the effectiveness, safety and utilisation of cobimetinib and vemurafenib in patients with and without brain metastasis with BRAF V600 mutant melanoma under real world conditions. The RMP version 5.0 has also been submitted.
  • Request for supplementary information adopted with a specific timetable.

CHMP-CAT assessed procedures

• Breyanzi (lisocabtagene maraleucel /lisocabtagene maraleucel) - Bristol-Myers Squibb Pharma EEIG
  • Request for supplementary information adopted with a specific timetable.
• Imlygic (talimogene laherparepvec) - Amgen Europe B.V.
  • To update the SmPC (section 6.6) and PIL (Thawing Imlygic vials) to revise the time for complete vial thaw from "approximately 30 minutes" to “the time to achieve complete vial thaw is expected to be 30 to 70 minutes, depending on the ambient temperature.” The MAH took the opportunity to introduce minor editorial changes in section 4.8 of the SmPC.
  • Positive Opinion adopted by consensus on 15.09.2022.

PRAC assessed ATMP procedures

• Imlygic (talimogene laherparepvec) - Amgen Europe B.V.
  • Submission of the final report from study 20120139 listed as a category 3 study in the RMP in order to fulfil MEA/004. This is a multicenter, observational registry study to evaluate the survival and long-term safety of subjects who previously received talimogene laherparepvec in Amgen or BioVEX sponsored clinical trials.
  • Request for supplementary information adopted with a specific timetable.

Unclassified procedures and worksharing procedures of type I variations

• Herceptin; MabThera - Roche Registration GmbH
  • Positive Opinion adopted by consensus on 01.09.2022.

Information on withdrawn type II variation / WS procedure

• Abevmy (bevacizumab) - Mylan IRE Healthcare Limited
  • The MAH withdrew the procedure on 07.09.2022.

CHMP assessed procedures scope: Pharmaceutical aspects

• Caelyx pegylated liposomal (doxorubicin) - Baxter Holding B.V
• Imfinzi (durvalumab) - AstraZeneca AB
• Blitzima; Truxima - Celltrion Healthcare Hungary Kft.

CHMP assessed procedures scope: Non-Clinical and Clinical aspects

• Alecensa (alectinib) - Roche Registration GmbH
  • Submission of the final report from study JO28928 (J-ALEX) a Randomized Phase III Open-Label Study Comparing the Efficacy and Safety of Crizotinib and CH5424802 in ALK-Positive Advanced or Recurrent Non-Small Cell Lung Cancer.
• Nerlynx (neratinib) - Pierre Fabre Medicament
  • Update of section 5.2 of the SmPC in order to add information on distribution and on the effect of neratinib on CYP substrates based on non-clinical studies XT218036 and 20325317; study XT218036 was designed to evaluate neratinib as a substrate of the human transporters OATP1B1 and OATP1B3 and study 20325317 objective was to determine the inactivation kinetic constants (kinact and KI) of Neratinib and M6 for the human cytochrome P450 (CYP) isoenzymes 2B6 and 3A4 using pooled human liver microsomes (HLM). In addition, the MAH is also taking this opportunity to introduce editorial changes.

CHMP-PRAC assessed procedures

• Revlimid (lenalidomide) - Bristol-Myers Squibb Pharma EEIG
  • Update of section 4.4 of the SmPC, EMA/CHMP/770516/2022 Page 70/75 Annex IID and Article 127a and the tools/documents included in the Educational Healthcare Professional Kit, in order to harmonise the terminology utilised in the RMP and PI documents relating to the safety concern of teratogenicity and its risk minimization measure of the Pregnancy Prevention Plan across the 3 IMiDs. These proposed changes will only have a limited impact on the National Competent Authority (NCA)-approved content/text of the educational materials, and the key messages to the HCP and patients. Furthermore, the regulatory obligations regarding the PPP will not be impacted. The MAH is also taking the opportunity to update the RMP with PASS Protocol milestones. The updated RMP version 38 was provided.
• Thalidomide BMS (thalidomide) - Bristol-Myers Squibb Pharma EEIG
  • Update of section 4.4 of the SmPC, Annex IID and Article 127a and the tools/documents included in the Educational Healthcare Professional Kit, in order to harmonise the terminology utilised in the RMP and PI documents relating to the safety concern of teratogenicity and its risk minimisation measure of the Pregnancy Prevention Plan across the 3 IMiDs. These proposed changes will only have a limited impact on the National Competent Authority (NCA)-approved content/text of the educational materials, and the key messages to the HCP and patients. Furthermore, the regulatory obligations regarding the PPP will not be impacted. The MAH is also taking the opportunity to update the RMP with PASS Protocol milestones, and to make some editorial changes in the labelling. The updated RMP version 20 was provided.

Unclassified procedures and worksharing procedures of type I variations

• Herceptin; MabThera - Roche Registration GmbH

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