Europe: Oncology CHMP Minutes for June 2023
Minutes from the EMA’s Committee for Medicinal Products for Human Use (CHMP) meeting on 19-22 June 2023 released on the 06th of September 2023. Items of interest listed below:
Initial applications
- Initial applications; List of outstanding issues (Day 180; Day 120 for procedures with accelerated assessment timetable)
- talquetamab - PRIME - Orphan - Accelerated assessment - Janssen-Cilag International N.V.; monotherapy treatment of adult patients with relapsed and refractory multiple myeloma. The Committee adopted a list of outstanding issues with a specific timetable.
- Initial applications; List of questions (Day 120; Day 90 for procedures with accelerated assessment timetable)
- sugemalimab - Treatment of adults with metastatic non-small cell lung cancer (NSCLC)
The Committee adopted the CHMP recommendation and scientific discussion together with the list of questions.
- Update on on-going initial applications for Centralised procedure
- aumolertinib - Treatment of non-small cell lung cancer
The CHMP agreed to the request by the applicant for an extension to the clock stop to respond to the list of questions adopted in March 2023.
- Extension of marketing authorisation according to Annex I of Commission Regulation (EC) No 1234/2008; Opinion
- Adtralza - tralokinumab - LEO Pharma A/S
The Committee confirmed that all issues previously identified in this application had been addressed. The Committee adopted a positive opinion by consensus together with the CHMP Assessment Report and translation timetable.
- Erleada - apalutamide - Janssen-Cilag International N.V.
Scope: “Extension application to add a new strength (240 mg) film-coated tablets grouped with the IB variation (C.I.z). The RMP (version 6.1) has also been submitted. C.I.z (IB): to align the SmPC/PL for Erleada 60 mg with the SmPC/PL proposed for the registration of the new Erleada film-coated tablet strength, 240 mg. The PL for Erleada 60 mg is proposed to be updated to ensure consistency. In addition, few minor revisions are proposed to the SmPC for Erleada 60 mg, to align the SmPC proposed for the 240 mg strength: - SmPC sections 5.1 and 5.2: Orthographic corrections - SmPC section 6.5: Further details on the description of the current packaging have been added, this change does not result from a change to the container. - SmPC section 6.6: The title of the section has been aligned with QRD template.” The Committee adopted a positive opinion by consensus together with the CHMP Assessment Report and translation timetable.
- Extension of marketing authorisation according to Annex I of Commission Regulation (EC) No 1234/2008; Day 120 List of question
- Lumykras - sotorasib - Amgen Europe B.V.
Scope: “Extension application to add a new strength of 240 mg film-coated tablet.” Action: For adoption The Committee discussed the issues identified in this application relating to quality and PK aspects. The Committee adopted the CHMP recommendation and scientific discussion together with the list of questions.
- Talzenna - talazoparib - Pfizer Europe MA EEIG
Scope: “Extension application for Talzenna to introduce a new strength of 0.1 mg hard capsules, grouped with a type II variation (C.I.6.a) in order to extend the indication for Talzenna in combination with enzalutamide for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC), based on final results from study C3441021 (TALAPRO-2) as well as supplemental data from study C3441006 (TALAPRO-1). Study C3441021 (TALAPRO-2) is a randomized, double-blind, placebo-controlled, phase 3 study of talazoparib in combination with enzalutamide in mCRPC, while study C3441006 (TALAPRO-1) is a phase 2, open-label, response rate study of talazoparib in men with DNA repair defects and mCRPC who previously received taxane-based chemotherapy and progressed on at least one novel hormonal agent. As a consequence, sections 1, 2, 3, 4.1, 4.2, 4.5, 4.7, 4.8, 5.1, 5.2, 6.1, 6.5 and 8 of the SmPC are updated. The Package Leaflet and Labelling are updated in accordance. Version 1.1 of the RMP has also been submitted. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI.” The Committee discussed the issues identified in this application relating to clinical safety. The Committee adopted the CHMP recommendation and scientific discussion together with the list of questions.
- Type II variations - variation of therapeutic indication procedure according to Commission Regulation (EC) No 1234/2008; Opinions or Requests for supplementary information
- Abecma - idecabtagene vicleucel - Orphan - ATMP - Bristol-Myers Squibb Pharma EEIG
Scope: “Extension of indication to include treatment of adult patients with relapsed and refractory multiple myeloma (RRMM) who have received at least two prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD-38 antibody and have demonstrated disease progression on the last therapy for Abecma (idecabtagene vicleucel, ide-cel), based on results from study BB2121-MM-003 (MM-003, KarMMa-3). This is a Phase 3, multicentre, randomised, open-label study to compare the efficacy and safety of ide-cel versus standard regimens in subjects with RRMM. As a consequence, sections 2.1, 2.2, 4.1, 4.2, 4.4, 4.5, 4.8, 5.1, 5.2, 6.3, 6.4 and 6.6 of the SmPC are updated. The Package Leaflet and Labelling are updated in accordance. Version 3.0 of the RMP has also been submitted. Furthermore, the PI is brought in line with the Guideline on core SmPC, Labelling and Package Leaflet for advanced therapy medicinal products (ATMPs) containing genetically modified cells.”, Request for 1 year of market protection for a new indication (Article 14(11) of Regulation (EC) 726/2004) Action: For adoption The CHMP was updated on discussions at the CAT. The Committee discussed the issues identified in this application relating to the RMP. The Committee endorsed the request for supplementary information with a specific timetable as adopted by CAT. 5.1.2. Adcetris - brentuximab vedotin - Orphan - EMEA/H/C/002455/II/0107 Takeda Pharma A/S Rapporteur: Johann Lodewijk Hillege Scope: “Extension of indication to include treatment of adult patients with previously untreated CD30+ advanced (including Stage III) Hodgkin lymphoma (HL), in combination with doxorubicin, vinblastine and dacarbazine (AVD), for Adcetris, based on the second interim analysis of OS data from ECHELON-1 study (C25003); this is a randomized, openlabel, phase 3 trial of A+AVD versus ABVD as frontline therapy in patients with advanced classical HL. As a consequence, sections 4.1 and 5 of the SmPC are updated.” The Committee discussed the issues identified in this application relating to clinical efficacy. The Committee adopted a request for supplementary information with a specific timetable.
- Brukinsa - zanubrutinib - BeiGene Ireland Ltd
Scope: “Extension of indication to include in combination with obinutuzumab treatment of adult patients with relapsed or refractory follicular lymphoma who have received at least two prior systemic treatments for Brukinsa; based on results from studies BGB-3111-212 and BGB-3111-GA101-001. BGB-3111-212 is an ongoing international, Phase 2, open-label, randomized (2:1), active control study of zanubrutinib plus obinutuzumab (Arm A) versus obinutuzumab monotherapy (Arm B) in patients with R/R FL. The primary efficacy endpoint is overall response rate (ORR); while BGB-3111-GA101-001 is a Phase 1b Study to Assess Safety, Tolerability and Antitumor Activity of the Combination of BGB-3111 with Obinutuzumab in Subjects with B-Cell Lymphoid Malignancies. As a consequence, sections 4.1, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 3.1 of the RMP has also been submitted. In addition, the MAH took the opportunity to implement editorial changes to the SmPC.” The Committee discussed the issues identified in this application relating to nonclinical, clinical, pharmacovigilance and RMP aspects. The Committee adopted a request for supplementary information with a specific timetable.
- Imjudo - tremelimumab - AstraZeneca AB
Scope: “Extension of indication to include in combination with durvalumab and platinumbased chemotherapy, the first-line treatment of adults with metastatic non-small cell lung cancer (NSCLC) with no sensitising EGFR mutations or ALK positive mutations for Imjudo, based on the final analysis from the pivotal study D419MC00004, a Randomised, Multicenter, Open-Label, Comparative Global Study to Determine the Efficacy of Durvalumab or Durvalumab and Tremelimumab in Combination with Platinum-Based Chemotherapy for First-Line Treatment in Patients with Metastatic Non Small-Cell Lung Cancer (NSCLC) (POSEIDON). As a consequence, sections 2, 4.1, 4.2, 4.4, 4.5, 4.8, 5.1, 5.2, 5.3 and 6.6 of the SmPC are updated. The Package Leaflet is updated in accordance. In addition, the MAH took the opportunity to include editorial changes.” Request for Supplementary Information adopted on 25.05.2023. The Committee confirmed that all issues previously identified in this application had been addressed. The Committee adopted a positive opinion by consensus together with the CHMP Assessment Report and translation timetable. The summary of opinion was circulated for information.
- Keytruda - pembrolizumab - Merck Sharp & Dohme B.V.
Scope: “Extension of indication to include in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant, treatment of resectable stage II, IIIA, or IIIB (T3 4N2) non-small cell lung carcinoma in adults for Keytruda based on study KEYNOTE-671, a phase III, randomized, double-blind trial of platinum doublet chemotherapy +/- pembrolizumab as neoadjuvant/adjuvant therapy for participants with resectable stage II, IIIA, and resectable IIIB (T3-4N2) nonsmall cell lung cancer. As a consequence, sections 4.1, 4.2 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 41.1 of the RMP has also been submitted.” The Committee discussed the issues identified in this application relating to clinical efficacy aspects. The Committee adopted a request for supplementary information with a specific timetable.
- Keytruda - pembrolizumab - Merck Sharp & Dohme B.V.
Scope: “Extension of indication to include in combination with chemotherapy the first-line treatment of locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma in adults based on study KEYNOTE-859, a randomized, double-blind phase 3 trial, evaluating Keytruda in combination with chemotherapy compared to placebo in combination with chemotherapy for the first-line treatment of patients with HER2-negative locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. As a consequence, sections 4.1 and 5.1 of the SmPC are updated. The Package Leaflet and Annex II are updated in accordance. Version 42.1 of the RMP has also been submitted.” The Committee discussed the issues identified in this application relating to clinical efficacy aspects. The Committee adopted a request for supplementary information with a specific timetable.
- Lonsurf - trifluridine / tipiracil - Les Laboratoires Servier
Scope: “Extension of indication to include treatment of patients with refractory metastatic colorectal cancer, for Lonsurf in combination with bevacizumab based on results from study SUNLIGHT (CL3-95005-007); This is an open-label, randomised, phase III study comparing trifluridine/tipiracil in combination with bevacizumab to trifluridine/tipiracil monotherapy in patients with refractory metastatic colorectal cancer. 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. The updated RMP version 10 has also been submitted. In addition, the MAH took the opportunity to update section 4.6 of the SmPC and the package leaflet accordingly.” Request for Supplementary Information adopted on 25.05.2023. The Committee confirmed that all issues previously identified in this application had been addressed. The Committee adopted a positive opinion by consensus together with the CHMP Assessment Report and translation timetable. The summary of opinion was circulated for information.
- Pepaxti - melphalan flufenamide - Oncopeptides AB
Scope: “Extension of indication to include treatment of patients with Multiple Myeloma who have received at least two prior lines of therapies for Pepaxti, based on final results from study OP-103 OCEAN; this is a randomized, open-label phase III study in patients with relapsed or refractory multiple myeloma following two to four lines of prior therapies and who were refractory to lenalidomide and the last line of therapy. As a consequence, sections 4.1, 4.4, 4.8 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 1.1 of the RMP has also been submitted. In addition, the MAH took the opportunity to implement editorial changes in the SmPC.”
Request for Supplementary Information adopted on 30.03.2023. The Committee discussed the issues identified in this application relating to clinical and RMP aspects. The Committee adopted a 2nd request for supplementary information with a specific timetable.
Post-authorisation issues
- 9.1. Post-authorisation issues
- Blenrep - belantamab mafodotin - Orphan GlaxoSmithKline (Ireland) Limited
Scope: Renewal of conditional marketing authorization. Request for Supplementary Information adopted on 26.04.2023. The Committee discussed the issues identified in this application. The Committee adopted a 2nd request for supplementary information with a specific timetable. The CHMP agreed to consult a SAG and adopted a list of questions to this expert group.
- Brintellix - vortioxetine - H. Lundbeck A/S
Scope: “Update of sections 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC in order to include clinically relevant information on the efficacy, safety, tolerability and PK of vortioxetine in the paediatric population based on final results from studies 12709A, 12712A and 12712B. Study 12709A is an interventional, randomized, double-blind, placebo-controlled, activereference (fluoxetine), fixed-dose study of vortioxetine in paediatric patients aged 7 to 11 years, with Major Depressive Disorder (MDD) to evaluate efficacy and safety. Whereas studies 12712A and 12712B are 2 open-label, long-term safety and efficacy studies in children and adolescents: one 6-month extension study (study 12712A) to studies 12709A and 12710A, and one 18-month extension study (study 12712B) to study 12712A. The Package Leaflet is updated accordingly. In addition, updates are proposed in section 4.5 and package leaflet section 2 in relation to NSAIDs as well as updates to the package leaflet section 4 to align SmPC wording on sexual dysfunction.” Request for Supplementary Information adopted on 30.03.2023, 15.12.2022. The Committee discussed the issues identified in this application relating to SmPC aspects. The Committee adopted a 3rd request for supplementary information with a specific timetable.
Annex
B POST-AUTHORISATION PROCEDURES OUTCOMES
B.1. Annual re-assessment outcomes
B.1.1. Annual reassessment for products authorised under exceptional circumstances
Evoltra - clofarabine - Sanofi B.V., Rapporteur: Alexandre Moreau,
Positive Opinion adopted by consensus together with the CHMP assessment report. The Marketing Authorisation remains under exceptional circumstances
B.2. RENEWALS OF MARKETING AUTHORISATIONS OUTCOMES
B.2.2. Renewals of Marketing Authorisations for unlimited validity
Lenalidomide Accord - lenalidomide - Accord Healthcare S.L.U.,
Request for Supplementary Information adopted on 26.04.2023. 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.
Ogivri - trastuzumab - Viatris Limited,
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.
POTELIGEO - mogamulizumab – Orphan - Kyowa Kirin Holdings B.V.,
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
Venclyxto - venetoclax - AbbVie Deutschland GmbH & Co. KG,
Request for Supplementary Information adopted on 26.04.2023. Positive Opinion adopted by consensus together with the CHMP assessment report. 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.
B.2.3. Renewals of Conditional Marketing Authorisations
Blenrep - belantamab mafodotin – Orphan - GlaxoSmithKline (Ireland) Limited
Request for supplementary information adopted with a specific timetable.
B.3. POST-AUTHORISATION PHARMACOVIGILANCE OUTCOMES
Imbruvica (ibrutinib) - Janssen-Cilag International N.V.
The CHMP, having considered in accordance with Article 28 of Regulation (EC) No 726/2004 the PSUR on the basis of the PRAC recommendation and the PRAC assessment report as appended, recommends by consensus the variation to the terms of the marketing authorisation(s) for the above mentioned medicinal product(s), concerning the following change(s):
Update of section 4.8 of the SmPC to add the adverse reaction Acute kidney injury with a frequency common and to add the adverse reaction Pyogenic granuloma with a frequency uncommon. The Package leaflet is updated accordingly.
Vargatef (nintedanib) - Boehringer Ingelheim International GmbH
The CHMP, having considered in accordance with Article 28 of Regulation (EC) No 726/2004 the PSUR on the basis of the PRAC recommendation and the PRAC assessment report as appended recommends by consensus the variation to the terms of the marketing authorisation(s) for the above mentioned medicinal product(s), concerning the following change(s):
Update of section 4.4 of the SmPC to amend a warning/precaution regarding gastrointestinal perforations and ischaemic colitis. The package leaflet is updated accordingly.
Calquence (acalabrutinib), AstraZeneca AB
The CHMP, having considered in accordance with Article 28 of Regulation (EC) No 726/2004 the PSUR on the basis of the PRAC recommendation and the PRAC assessment report as appended recommends by consensus the variation to the terms of the marketing authorisation(s) for the above mentioned medicinal product(s), concerning the following change(s):
Update of section 4.8 of the SmPC to add the adverse reaction hypertension with frequencies common and very common for acalabrutinib monotherapy and combination therapy respectively. The package leaflet is updated accordingly.
Retsevmo (selpercatinib), Eli Lilly Nederland B.V.,
The CHMP, having considered in accordance with Article 28 of Regulation (EC) No 726/2004 the PSUR on the basis of the PRAC recommendation and the PRAC assessment report as appended, recommends by consensus the variation to the terms of the marketing authorisation(s) for the above mentioned medicinal product(s), concerning the following change(s):
Update of sections 4.4, 4.5 and 4.8 of the SmPC to add the adverse reaction hypothyroidism with a frequency very common, including a warning/precaution regarding relevant monitoring requirements. The package leaflet is updated accordingly.
EPARs / WPARs
Pylclari - piflufolastat (18f) - Curium Pet France, imaging in patients undergoing oncologic diagnostic procedures when increased expression of prostate specific membrane antigen is a diagnostic target, New active substance (Article 8(3) of Directive No 2001/83/EC) For information only. Comments can be sent to the PL in case necessary.
TYPE II VARIATION, WORKSHARING PROCEDURE OUTCOMES
- CHMP assessed procedures scope: Pharmaceutical aspects
Azacitidine betapharm - azacitidine - betapharm Arzneimittel GmbH
Request for Supplementary Information adopted on 22.06.2023 with a specific timetable.
Lonsurf - trifluridine / tipiracil - Les Laboratoires Servier,
Request for Supplementary Information adopted on 19.01.2023. Positive Opinion adopted by consensus on 15.06.2023.
Ontruzant - trastuzumab - Samsung Bioepis NL B.V.,
Positive Opinion adopted by consensus on 15.06.2023.
Pluvicto - lutetium (177Lu) vipivotide tetraxetan - Novartis Europharm Limited,
Request for Supplementary Information adopted on 01.06.2023 with a specific timetable.
POTELIGEO - mogamulizumab - Kyowa Kirin Holdings B.V.,
Request for Supplementary Information adopted on 22.06.2023, 14.04.2023 with a specific timetable.
CHMP assessed procedures scope: Non-Clinical and Clinical aspects
CABOMETYX - cabozantinib - Ipsen Pharma
“Update of sections 4.4 and 4.8 of the SmPC in order to add a new warning on Vanishing Bile Positive Opinion adopted by consensus on 08.06.2023. Duct Syndrome (VBDS), to add embolism arterial to the list of adverse drug reactions (ADRs) with frequency Uncommon and to add vanishing bile duct syndrome to the list of adverse drug reactions (ADRs) with frequency Not known based on the cumulative review of the global safety database and literature search. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI.”
Kisqali - ribociclib - Novartis Europharm Limited,
“Grouped application comprising two type II variations as follows:
- Update of section 5.2 of the SmPC in order to update absorption information based on final results from study CLEE011A2117, a Phase I, single center, two-period, two-treatment, open label, randomized crossover study to investigate the absolute bioavailability of a single oral dose of 600 mg of ribociclib relative to an intravenous (i.v.) infusion of 150 mg ribociclib in healthy subjects.
- Update of sections 4.2 and 4.5 of the SmPC in order to update the recommended dose modification when ribociclib is administered in combination with CYP3A4 inhibitors and update the drug-drug interaction information on substances that may increase ribociclib plasma concentrations based on the updated PBPK modelling.
In addition, the MAH took this opportunity to introduce minor editorial changes to the Package Leaflet.”
Request for Supplementary Information adopted on 22.06.2023 with a specific timetable.
Orgovyx - relugolix - Accord Healthcare S.L.U.,
“Update of section 4.5 of the SmPC based on final results from study MVT601-9039; this is an In vitro Interaction Study of Relugolix with human OATP2B1 Uptake Transporter.” Positive Opinion adopted by consensus on 01.06.2023.
Rydapt - midostaurin – Orphan, Novartis Europharm Limited,
“Update of section 4.8 of the SmPC in order to add “Acute febrile neutrophilic dermatosis” to the list of adverse drug reactions (ADRs) with frequency not known based on pre-clinical data, clinical trial datasets, scientific literature and safety databases. The Package Leaflet is updated accordingly. The MAH took the occasion to also include some editorial/formatting changes in the product information. The MAH has also taken the occasion to align the annex A to the correct expression of pack size as included in the registered system (Siamed).” Request for Supplementary Information adopted on 22.06.2023.
Scemblix - asciminib – Orphan - Novartis Europharm Limited,
“Grouped application comprising two type II variations as follows:
- Submission of the final reports from studies DMPK-R2200470 (REC). This is an in vitro evaluation of inducibility of OATP1V1, MDR1 and CYP3A4 by asciminib using human hepatocytes.
- Submission of the final report from study DMPK-R2270399 (REC). This is a physiologically based PK modelling and simulations to characterize the effect of cyclodextrins on the exposure of asciminib.”
Request for Supplementary Information adopted on 15.06.2023.
TAGRISSO - osimertinib - AstraZeneca AB,
“Update of sections 4.2, 4.4 and 4.8 of the SmPC in order to modify the posology recommendations in the case of toxic epidermal necrolysis (TEN), add it as a new warning and add it to the list of adverse drug reactions (ADRs) with frequency uncommon and to update the frequency of interstitial lung disease (ILD) based on an internal safety information review. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI.” Opinion adopted on 22.06.2023.
Tecvayli - teclistamab - Janssen-Cilag International N.V.,
“Update of sections 4.2, 4.6 and 5.2 of the SmPC in order to revise the dosing schedule, amend recommendations on contraception and breast-feeding and to update pharmacokinetic information, based on the latest data available; the Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI and update the list of local Positive Opinion adopted by consensus on 22.06.2023.
TEPMETKO - tepotinib - Merck Europe B.V.,
“Update of sections 4.5 and 5.2 of the SmPC in order to remove interactions with ‘CYP and P-gp inducers’ and ‘dual strong CYP3A and P-gp inhibitors, and P-gp inhibitors’ and to update pharmacokinetic information based on final results from the drug-drug interaction (DDI) studies MS200095-0051 and MS200095-0053. Study MS200095-0051 is a phase 1, open-label, single-sequence, cross-over study to evaluate the effect of multiple doses of carbamazepine on single-dose tepotinib pharmacokinetics in healthy participants, while study MS200095-0053 is a phase 1, open-label, single-sequence, cross-over study to evaluate the effect of multiple doses of itraconazole on single-dose tepotinib pharmacokinetics in healthy participants. The Package Leaflet is updated accordingly. In addition, the MAH took the opportunity to introduce minor changes to the PI.” Opinion adopted on 15.06.2023.
TUKYSA - tucatinib - Seagen B.V.,
“Submission of the final report from study ONT380-206 (HER2CLIMB) listed as a PAES in the Annex II of the Product Information. This is a phase 2 randomized, double-blinded, controlled study of tucatinib vs. placebo in combination with capecitabine and trastuzumab in patients with pretreated unresectable locally advanced or metastatic HER2+ breast carcinoma. The Annex II is updated accordingly.” Request for Supplementary Information adopted on 22.06.2023.
Vargatef - nintedanib - Boehringer Ingelheim International GmbH,
“C.I.4: Update of section 5.2 of the SmPC in order to improve the Positive Opinion adopted by consensus on 22.06.2023 recommendation for the administration of nintedanib based on food compatibility data. In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet and to introduce minor editorial changes to the PI.” Opinion adopted on 22.06.2023.
- CHMP-PRAC assessed procedures
Enhertu - trastuzumab deruxtecan - Daiichi Sankyo Europe GmbH,
“Update of sections 4.8, 5.1 and 5.2 of the SmPC in order to update safety, efficacy and pharmacokinetic information based on data from study DS8201-A-U301 and study DS8201-A-U302. Study U301 was a Phase 3, randomized, 2-arm, open-label, multicenter study designed to compare the safety and efficacy of T-DXd vs TPC in HER2-positive, unresectable and/or metastatic BC subjects who were resistant or refractory to T-DM1. Study U302 was a Phase 3, multicenter, randomized, open-label, 2-arm, active-controlled study in subjects with unresectable and/or metastatic HER2-positive (IHC 3+ or ISH-positive) BC previously treated with trastuzumab plus taxane in the advanced/metastatic setting or who had progressed within 6 months after neoadjuvant or adjuvant treatment involving a regimen including trastuzumab plus taxane. The Package Leaflet and Annex II are updated accordingly. The updated RMP version 4.1 has also been request for supplementary information adopted with a specific timetable.
GAVRETO - pralsetinib - Roche Registration GmbH,
“Update of sections 4.8, 5.1 and 5.2 of the SmPC in order to update efficacy and safety information in the treatment of adult patients with RET fusion-positive advanced NSCLC based on final results (NSCLC indication) from study ARROW/BO42863, a Phase 1/2 Study of the Highly-selective RET Inhibitor, BLU 667, in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer (NSCLC), and Other Advanced Solid Tumours listed as a specific obligation in the Annex II. The RMP version 1.5 has also been submitted.” Opinion adopted on 22.06.2023.
GAVRETO - pralsetinib - Roche Registration GmbH,
“Update of sections 4.2, 4.4 and 4.5 of the SmPC in order to amend posology recommendations, warnings and drug-drug interaction information regarding the coadministration with CYP3A4 inhibitors, P-gp inhibitors and CYP3A4 inducers based on final results from the DDI study GP43162, listed as a category 3 study in the RMP, as well as results from the physiologically based pharmacokinetic (PBPK) analyses summarised in the PBPK Report 1120689. Study GP43162 is a phase 1, openlabel, fixed-sequence study to evaluate the effect of a single dose of cyclosporine on the single dose pharmacokinetics of pralsetinib in healthy subjects. The RMP version 1.6 has also been submitted.” Request for Supplementary Information adopted on 22.06.2023, 30.03.2023.
Imnovid - pomalidomide – Orphan - 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 Positive Opinion adopted by consensus on 08.06.2023 materials, and the key messages to the HCP and patients. Furthermore, the regulatory obligations regarding the PPP will not be impacted. The updated RMP version 16 was provided.”
Piqray - alpelisib - Novartis Europharm Limited,
“Update of sections 4.5 and 5.2 of the SmPC in order to update drug-drug interaction information, based on final results from study BYL719A2111; this is a phase 1, open-label, fixed-sequence, two-period drugdrug interaction (DDI) study evaluating the PK probe substrates for CYP3A4, CYP2B6, CYP2C8, CYP2C9, and CYP2C19 when administered either alone or in combination with repeated doses of alpelisib. The Annex II and Package Leaflet are updated accordingly. The RMP version 6.0 has also been submitted. In addition, the MAH took the opportunity to introduce minor editorial changes to the PI.”
XOSPATA - gilteritinib – Orphan - Astellas Pharma Europe B.V.,
“Update of sections 4.2 and 5.2 in order to update the information on renal impairment based on final results from study 2215-CL-0114, listed as a category 3 study in the RMP. Study 2215-CL0114 is a phase 1, single-dose, open-label study to investigate the effect of renal impairment on gilteritinib pharmacokinetics, safety and tolerability in 9 participants with severe renal impairment compared to 8 participants with normal renal function. The RMP version 4.0 has also been submitted. In addition, the MAH took the opportunity to introduce editorial changes.”
- PRAC assessed procedures
CABOMETYX - cabozantinib - Ipsen Pharma
“Submission of the final report from study F-FR-60000-001 (CASSIOPE) listed as a category 3 study in the prospective, non-imposed and noninterventional study of cabozantinib tablets in adults with advanced renal cell carcinoma (RCC) following prior vascular endothelial growth factor (VEGF)-targeted therapy. The RMP version 7.0 has also been submitted.” Request for Supplementary Information adopted on 08.06.2023.
Revlimid - lenalidomide - Bristol-Myers Squibb Pharma EEIG,
“Submission of the final report from study CC-5013-MDS-010 listed as an obligation in the Annex II of the Product Information. This is a prospective noninterventional post-authorisation safety study (PASS), designed as a disease registry of patients with transfusion dependent IPSS low or intermediate-1-risk myelodysplastic syndromes (MDS) and isolated del(5q). Section D of the Annex II and the RMP (version 39) are updated accordingly.” Request for Supplementary Information adopted on 08.06.2023.
VARIATIONS – START OF THE PROCEDURE B.6.7. Type II Variations scope of the Variations: Extension of indication
CARVYKTI - ciltacabtagene autoleucel - Janssen-Cilag International NV,
“Extension of indication to include treatment of adult patients with relapsed and refractory multiple myeloma, who have received at least 1 prior therapy, including an IMiD and a PI, have demonstrated disease progression on or after the last therapy and are refractory to lenalidomide for CARVYKTI, based on interim results from study MMY3002 listed as a specific obligation (SOB/006) in the Annex II. This is an ongoing, Phase 3, randomized, open-label, multicentre study to determine whether treatment with cilta-cel provides an efficacy benefit compared to standard therapy in participants with relapsed and lenalidomiderefractory multiple myeloma. As a consequence, sections 4.1, 4.4, 4.5, 4.8, 5.1 and 5.2 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 4.1 of the RMP has also been submitted. In addition, the MAH took the opportunity to update Annex II of the PI. As part of the application the MAH is requesting a 1 -year extension of the market protection.”
Request for 1 year of market protection for a new indication (Article 14(11) of Regulation (EC) 726/2004)
Keytruda - pembrolizumab - Merck Sharp & Dohme B.V.,
“Extension of indication to include KEYTRUDA in combination with gemcitabine
- based chemotherapy for the first
-line treatment of locally advanced unresectable or metastatic biliary tract carcinoma in adults, based on final results from study KEYNOTE -966; this is a Phase 3 randomized, double blind study of Pembrolizumab plus Gemcitabine/Cisplatin versus Placebo plus Gemcitabine/Cisplatin as first
-line therapy in participants with advanced and/or unresectable biliary tract carcinoma. As a consequence, sections 4.1, 4.4 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 43.1 of the RMP has also been submitted.”
B.6.12. CHMP-CAT assessed procedures
Abecma - idecabtagene vicleucel - Orphan, ATMP - Bristol-Myers Squibb Pharma EEIG
Document Source: CHMP Minutes 19-22 June 2023