EMA: minute del CHMP (Onco-Ematologia)

Sono state rese disponibili le minute del CHMP relative ai meeting di marzo:

Initial applications; Opinions

• Carvykti (ciltacabtagene autoleucel) (PRIME)(Orphan)(ATMP) – Janssen-Cilag
  • Indication: treatment of multiple myeloma
  • The CHMP, based on the draft opinion prepared by the CAT, adopted a positive opinion recommending the granting of a conditional marketing authorisation.

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

• mosunetuzumab (Orphan) – Roche
  • Indication: refractory follicular lymphoma (FL)
  • The Committee adopted a list of outstanding issues with a specific timetable.
• melphalan flufenamide (Orphan) – Oncopeptides AB
  • Indication: treatment of multiple myeloma
  • The CHMP agreed on the need to consult a SAG and adopted a list of questions to this group.

Type II variations

• Imbruvica (ibrutinib) – Janssen-Cilag
  • Extension of the existing CLL indication to include combination treatment with venetoclax for previously untreated patients based on efficacy and safety data from phase 3 study GLOW and phase 2 study CAPTIVATE. The SmPC is revised to reflect the information on the combination with venetoclax. The PL is updated accordingly. The RMP version 18.4 has been submitted. Justification to support one-year extension of the marketing protection period is included in the submission.
  • The Committee adopted a request for supplementary information with a specific timetable.
• Kymriah (tisagenlecleucel)(Orphan)(ATMP) – Novartis
  • Extension of indication to include treatment of adult patients with follicular lymphoma (FL) after two or more lines of therapy who are refractory or relapsed during or within 6 months after completion of anti-CD20 antibody maintenance or relapsed after autologous haematopoietic stem cell transplantation (HSCT) for Kymriah. As a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC and corresponding sections in the Package Leaflet are updated accordingly. The RMP has been updated to version 4.0 to align with the indication extension. Lastly, the minor editorial corrections are made throughout the SmPC and package leaflet to align with the current QRD template version 10.2.
  • The Committee, based on the draft opinion prepared by the CAT, adopted a positive opinion by consensus together with the CHMP Assessment Report and translation timetable.
• Nexpovio (Selinexor) – Karyopharm
  • Group of variations including an extension of indication for Nexpovio in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy and a quality variation for the addition of a new pack size to align with the dose modification guidance for the new indication. Sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1 and 6.5 of the SmPC are updated to reflect the new indication and the new pack size. Annex II is updated to reflect the completion of the Specific Obligation. The Labelling and Package Leaflet are amended accordingly. The RMP (v 1.1) is amended consequently.
  • The Committee adopted a 3rd request for supplementary information with a specific timetable.
• Polivy (polatuzumab vedotin) (Orphan) – Roche
  • Extension of the indication to include: Polivy in combination with rituximab, cyclophosphamide, doxorubicin and prednisone, is indicated for the treatment of adult patients with previously untreated diffuse large B-cell lymphoma (DLBCL) based on the efficacy and safety data from the Pivotal Phase III study GO39942 (POLARIX). This submission fulfils SOB003 thus supporting the switch from CMA to full MA. Annexes I, II, IIIB are revised. The RMP is also updated.
  • The Committee adopted a positive opinion by consensus together with the CHMP Assessment Report and translation timetable.
• Vyxeos liposomal (daunorubicin / cytarabine) (Orphan) – Jazz Pharmaceuticals
  • Update of sections 4.4, 4.8, 5.1 and 5.2 of the SmPC to include relevant information in paediatric patients based on results from the paediatric clinical study AAML1421. The Package leaflet is updated accordingly.
  • The CHMP was reminded that the applicant withdrew the extension of indication part from the scope of this variation, instead proposing inclusion of relevant paediatric data in the product information based on results from study AAML1421.
  • The Committee adopted a positive opinion by consensus together with the CHMP Assessment Report and translation timetable.

Pre-submission issues

• Glofitamab (Orphan) – Roche
  • Indication: indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphomas (DLBCL), high grade B cell lymphoma (HGBCL) and primary mediastinal large B-cell lymphoma (PMBCL), after two or more lines of systemic therapy.
  • The CHMP did not agree to the request for accelerated assessment and adopted the briefing note and Rapporteurs’ recommendation on the Request for Accelerated Assessment.

Post-authorisation issues

• Adcetris (brentuximab vedotin)(orphan) – Takeda
  • Update of sections 4.8 and 5.1 of the SmPC, based on final results from study C25006, a multi-centre open-label, phase 4 study of 50 patients with r/r sALCL undertaken to further evaluate the efficacy and safety of brentuximab vedotin as a single agent in adult patients who had previously received at least 1 multiagent chemotherapy regimen. This study was listed as an interventional category 2 PASS in the RMP (SOB 010). In addition, the MAH took the opportunity to request the granting of a marketing authorisation not subject to specific obligations and valid for five years, in accordance with Article 14-a(8) of Regulation (EC) No 726/2004, thereby deleting SOB 010 from the annex II and of the reference to the conditional marketing authorisation from annex II and the package leaflet. The revised RMP version 16.1 has also been submitted. An editorial update under section 5.1 of the SmPC (update of the ATC code) has been implemented.
  • In addition, the CHMP, having considered the application as set out in the assessment report and having reviewed the data submitted by the marketing authorisation holder including the evidence concerning compliance with specific obligations, is of the opinion that the risk-benefit balance of the above mentioned medicinal product remains favourable, that all specific obligations laid down in Annex II have been fulfilled and that comprehensive data supports a favourable benefit-risk balance of the above mentioned medicinal product. Therefore, pursuant to Article 14-a(8) of Regulation (EC) No 726/2004, the CHMP recommends by consensus the granting of a marketing authorisation in accordance with Article 14(1) of Regulation (EC) No 726/2004 for the above mentioned medicinal product for which the draft Summary of Product Characteristics is set out in Annex I.
  • The Committee adopted a positive opinion by consensus together with the CHMP Assessment Report and translation timetable.

Renewals of Marketing Authorisations for unlimited validity

• Rydapt (midostaurin)(Orphan) - Novartis
  • the CHMP believed the renewal of the marketing authorisation can be granted with unlimited validity.

Renewals of Conditional Marketing Authorisations

• Nexpovio (Selinexor) - Karyopharm Europe
  • The CHMP believed the renewal for this conditional Marketing Authorisation can be granted. The Marketing Authorisation remains conditional.

POST-AUTHORISATION PHARMACOVIGILANCE OUTCOMES

• CAPS: Blenrep (belantamab mafodotin) – GSK
  • 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): In view of available data on pneumonitis from spontaneous reports including in one case a reasonable temporal relationship and absence of other causal explanations and in view of a non-clinical signal and plausible mechanism of action, the PRAC considers a causal relationship between belantamab mafodotin and pneumonitis is at least a reasonable possibility. Therefore, changes to the wording in section 4.4 are proposed by deleting “although a causal association has not been established” and in addition to update section 4.8 with ‘pneumonitis’ as an ADR.

CHMP assessed procedures scope: Pharmaceutical aspects

• Mylotarg (gemtuzumab ozogamicin)(Orphan) - Pfizer
  • Positive Opinion adopted by consensus on 10.03.2022.

• Polivy (polatuzumab vedotin) (Orphan) – Roche
  • Request for Supplementary Information adopted on 03.02.2022.

• Spectrila (asparaginase) - medac Gesellschaft fur klinische Spezialpraparate mbH
  • Positive Opinion adopted by consensus on 24.03.2022.

CHMP assessed procedures scope: Non-Clinical and Clinical aspects

• Iclusig (ponatinib)(Orphan) - Incyte Biosciences Distribution B.V
  • “Update of sections 4.2, 4.4, 4.8 and 5.1 of the SmPC based on results from the OPTIC study (AP24534-14-203) listed as a specific obligation in the Annex II. This is a randomised, open-label, Phase 2 trial of ponatinib in patients with chronic myeloid leukaemia to characterise the efficacy and safety of ponatibib over a range of doses; the Package Leaflet is updated accordingly.”
  • Positive Opinion adopted by consensus on 24.03.2022.

CHMP-PRAC assessed procedures

• ADCETRIS (brentuximab vedotin) – Takeda Pharma
  • “Update of sections 4.8 and 5.1 of the SmPC, based on final results from study C25006, a multi-centre open-label, phase 4 study of 50 patients with r/r sALCL undertaken to further evaluate the efficacy and safety of brentuximab vedotin as a single agent in adult patients who had previously received at least 1 multiagent chemotherapy regimen. This study was listed as an interventional category 2 PASS in the RMP (SOB 010). In addition, the MAH took the opportunity to request the granting of a marketing authorisation not subject to specific obligations and valid for five years, in accordance with Article 14-a(8) of Regulation (EC) No 726/2004, thereby deleting SOB 010 from the annex II and of the reference to the conditional marketing authorisation from annex II and the package leaflet. The revised RMP version 16.1 has also been submitted. An editorial update under section 5.1 of the SmPC (update of the ATC code) has been implemented. In addition, the CHMP, having considered the application as set out in the appended assessment report and having reviewed the data submitted by the marketing authorisation holder including the evidence concerning compliance with specific obligations, is of the opinion that the risk-benefit balance of the above mentioned medicinal product remains favourable, that all specific obligations laid down in Annex II have been fulfilled and that comprehensive data supports a favourable benefit-risk balance of the above mentioned medicinal product. Therefore, pursuant to Article 14-a(8) of Regulation (EC) No 726/2004, the CHMP recommends by consensus the granting of a marketing authorisation in accordance with Article 14(1) of Regulation (EC) No 726/2004 for the above mentioned medicinal product for which the draft Summary of Product Characteristics is set out in Annex I.”
  • Positive opinion adopted on 24.03.2022.
• MabThera (rituximab) – Roche
  • “Submission of the final report from study MA28150 (RITAZAREM) entitled Rituximab versus azathioprine as therapy for maintenance of remission for anti-neutrophilcytoplasm antibody-associated vasculitis listed as an interventional category 3 study in the RMP. The RMP version 23.0 has also been submitted.” Opinion adopted on 24.03.2022.
  • Positive Opinion adopted by consensus on 24.03.2022.
• Mylotarg (gemtuzumab ozogamicin)(Orphan) - Pfizer
  • “Update of sections 4.8, 5.1 and 5.2 of the SmPC based on the final results from study B176103; this is a single-arm, open-label, phase 4 study evaluating the QT interval, pharmacokinetics, and safety of gemtuzumab ozogamicin as a single-agent regimen in patients with relapsed or refractory CD33-positive Acute Myeloid Leukaemia. The RMP version 2.0 has also been submitted. In addition, the MAH took the opportunity to introduce some editorial changes in the product information.”
  • Request for supplementary information adopted with a specific timetable.

• Rydapt (midostaurin)(Orphan) - Novartis
  • “C.I.11.b Submission of the final report from study CPKC412E2301 listed as an obligation in the Annex II of the Product Information. This is a Phase III study to investigate the efficacy in elderly patients. A final pharmacogenomic report is also provided to fulfil MEA004. The Annex II and the RMP (submitted version 7.0) are updated accordingly.”
  • Request for Supplementary Information adopted on 10.03.2022.

CHMP-CAT assessed procedures

• Imlygic (talimogene laherparepvec) (ATMP) - Amgen
  • “Update of section 4.4 of the SmPC in order to add a new warning about the potential risk of hepatic haemorrhage with the transcutaneous intrahepatic route of administration of talimogene laherparepvec. In addition, the Marketing authorisation holder (MAH) took the opportunity to update the list of local representatives in the Package Leaflet.”
  • Positive opinion adopted on 24.03.2022, 18.03.2022.

Start of procedure for New Applications: timetables for information

• Ivosidenib (Orphan) - Les Laboratoires Servier,
  • Indication: treatment of acute myeloid leukaemia and treatment of metastatic cholangiocarcinoma

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

• Calquence (acalabrutinib) - AstraZeneca AB
  • “Extension application to introduce a new pharmaceutical form, film-coated tablet. A.6 - To change the ATC Code of acalabrutinib from L01XE51 to L01EL02.”
  • List of Questions adopted on 24.02.2022.
• thalidomide
  • Indication: treatment of multiple myeloma
  • List of Questions adopted on 16.09.2021.

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

• MINJUVI (tafasitamab) (Orphan) - Incyte Biosciences Distribution B.V.

CHMP assessed procedures scope: Pharmaceutical aspects

• Darzalex (daratumumab) (Orphan) - Janssen-Cilag
• Oncaspar (pegaspargase) - Les Laboratoires Servier,

CHMP assessed procedures scope: Non-Clinical and Clinical aspects

• Tasigna (nilotinib) - Novartis
  • “C.I.4: Update of section 4.8 of the SmPC in order to update the ADRs frequency category based on pooled safety data from 13 interventional clinical studies, 5 of which have not been previously assessed (CAMN107A2303 - 120 months data; CAMN107A2404; CAMN107E2401; CAMN107ECN02 and CAMN107EIC01). In addition, the MAH took the opportunity to merge the current 2 SmPCs (one for 150 mg and one for 50 mg/200 mg) into one single SmPC, by including all information from the 150 mg SmPC into the 50 mg/200 mg SmPC; and to implement editorial changes. The Package Leaflet is proposed to be updated accordingly. A.6: Update of nilotinib ATC code based on the last update of the WHO ATC index.”

• Vidaza (azacytidine) - Bristol-Myers Squibb
  • “Update of section 4.2 of the SmPC in order to include a statement advising health care professionals not to interchange azacitidine formulations (injectable versus oral), and update section 4.6 of the SmPC to revise the recommended duration of contraception use for women and men. The Package Leaflet is updated accordingly.”

• Vyxeos liposomal (daunorubicin / cytarabine)(Orphan) - Jazz Pharmaceuticals
  • “Update of sections 4.2, 4.4 and 5.2 of the SmPC to amend information and delete the existing warning for patients with renal impairment based on the final results from study CPX351-102 (PMR2): a phase 1, open-label, PK and safety study to evaluate the potential impact of renal impairment on the pharmacokinetics and safety of CPX-351 (Daunorubicin and Cytarabine) liposome for injection treatment in adult patients with hematologic malignancies.”

CHMP-CAT assessed procedures

• Kymriah (tisagenlecleucel) (Orhpan) (ATMP) - Novartis
  • “Submission of the final report from study CCTL019H2301 (BELINDA) listed as an obligation in the Annex II of the Product Information. This is a randomized open-label parallel-group multicentre Phase III trial to evaluate the efficacy and safety of tisagenlecleucel in adult patients with relapsed or refractory B-cell aggressive NHL after failure of rituximab and anthracycline containing first-line immune-chemotherapy. The Annex II is updated accordingly.”

Document source: CHMP Meeting Minutes March 2022