Qualifying Notice - Abecma

Biologic and Radiopharmaceutical Drugs Directorate
100 Eglantine Driveway
LCDC Building
Tunney's Pasture, A.L. 0601C
Ottawa, Ontario
K1A 0K9

Dossier ID: HC6-024-e232106
Control #: 244266

[employee name removed]
[employee title removed]
Celgene Inc.
2344 Alfred-Nobel, Suite 300
Saint-Laurent, Quebec, Canada
H4S 0A4
Email: [employee email removed]

Dear [employee name removed]:

This Notice of Compliance with Conditions (NOC/c)-Qualifying Notice, issued in accordance with the Health Canada NOC/c Policy, is to advise you that information submitted in support of the New Drug Submission (NDS) for Abecma (idecabtagene vicleucel), Control Number 244266, indicated for the treatment of adult patients with multiple myeloma who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and who are refractory to their last treatment, qualifies to be considered for authorisation under the NOC/c policy. In keeping with the provisions outlined in the NOC/c policy, the following additional information is required to complete the assessment:

1. A letter, signed by the Chief Executive Officer, or designated signing authority of Celgene Inc., a Bristol Myers Squibb company, indicating that you agree to have this submission considered under the NOC/c Policy. Please be reminded that in agreeing to accept an NOC under the NOC/c Policy, Celgene Inc. consents to the posting of the NOC/c-Qualifying Notice on Health Canada's website.
2. A draft Letter of Undertaking signed by the Chief Executive Officer, or designated signing authority, of Celgene Inc., having a form and content satisfactory to Health Canada, as indicated in the Guidance Document: Notice of Compliance with Conditions (NOC/c), including commitments to provide the following:

Confirmatory Studies

1. The report of the final analysis of [study name/number has been removed] – A phase 3, multicenter, open-label, randomized study comparing the safety and efficacy of Abecma (idecabtagene vicleucel) versus standard treatment regimens in the treatment of patients with relapsed and refractory multiple myeloma (RRMM). The timelines should be included in the Letter of Undertaking, including the earliest anticipated availability of the data to be filed as a Supplement to a New Drug Submission (SNDS)-confirmatory (SNDS-c).

Progress Reports of Confirmatory Trials and Other Ongoing Trials

2. The interim report of [study name/number has been removed] – A Phase 2, multi-cohort, open-label, multicenter study to determine the preliminary efficacy and safety of Abecma (idecabtagene vicleucel) in patients with RRMM and in patients with high-risk multiple myeloma having progressed within one year of initial treatment. The timelines for this additional interim study report should be included in the Letter of Undertaking and the interim study report may be filed when it becomes available or as part of the SNDS-c package.
3. On an annual basis, within 60 calendar days of the market authorization anniversary or a date agreed upon at the time of the issuance of the market authorization, status reports on the progress of ongoing confirmatory trials, as per section 3.2 and Appendix 4 of the Guidance Document: Notice of Compliance with Conditions (NOC/c). The details of the requirements for filing and termination of the annual status report as agreed upon by Celgene Inc. and Health Canada must be outlined in the Letter of Undertaking.

Safety Monitoring

4. Report all serious Adverse Reactions (AR) that occur in Canada and all serious unexpected ARs that occur outside of Canada within 15 days to the Marketed Health Products Directorate. Adverse Events (AE) and AR reports on marketed drugs occurring as part of confirmatory trials subject to clinical trial applications, as outlined in the Letter of Undertaking, must be sent to the Biologic and Radiopharmaceutical Drugs Directorate. Reporting must be conducted as per section 3.4.1 of the Guidance Document: Notice of Compliance with Conditions (NOC/c) and in accordance with current regulations and guidelines (e.g. Guidance for Industry: Reporting Adverse Reactions to Marketed Health Products and the Guidance for Clinical Trial Sponsors: Clinical Trial Applications).
5. Periodic Safety Update Reports or Periodic Benefit-Risk Evaluation Reports-C for NOC/c Products (PSUR-Cs or PBRER-Cs) every six months for the initial two years of market authorization and on an annual basis thereafter. PSUR-Cs/PBRER-Cs should be prepared in accordance with the E2C(R1) and E3C(R2) ICH Guideline, including format and content, as per section 3.4.2 of the Guidance Document: Notice of Compliance with Conditions (NOC/c);
6. A post-marketing, prospective, multi-center, observational study to assess the long-term safety of Abecma (idecabtagene vicleucel) and the risks of secondary malignancies in patients with RRMM. A minimum of one-thousand patients are to be enrolled in this observational study to assess long-term safety including the incidence of secondary malignancies against expected background incidence rates in this patient population. The enrolled patients in this study will be required to be followed for 15 years after receiving a single dose of Abecma (idecabtagene vicleucel) infusion.
7. Comply with the notification and reporting of specific issues of concern as outlined in Section 3.4.4 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).

Additional information

8. Provide the following information within the appropriate submission type in accordance with Health Canada guidance documents (i.e. Post-NOC Changes: Safety and Efficacy Document) if the labelling components are impacted or as post-clearance data if the labelling components are not impacted.
9. Receive pre-clearance by the Pharmaceutical Advertising Advisory Board (PAAB) for all promotional material related to Abecma (idecabtagene vicleucel) authorized under the NOC/c policy as per section 5.1 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
10. An outline of the agreed-upon advertising, labelling or distribution requirements, including a commitment to file revised Product Monographs under the appropriate submission type as information is made available as per section 4.3 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
11. An up-to-date, complete listing of ongoing additional clinical trials related to Abecma (idecabtagene vicleucel), appended to the draft Letter of Undertaking, as per Section 4.5 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
12. Copies of any marketing authorizations for Abecma (idecabtagene vicleucel) from any other drug regulatory authority as per Section 4.6 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).

I wish to advise you that this Qualifying Notice is being issued in accordance with Health Canada's guidances on the Management of Drug Submissions and Notice of Compliance with Conditions, respectively. Sponsors are instructed to submit a complete response (refer to Guidance Document: Notice of Compliance with Conditions) to the outstanding information within 30 calendar days of the date of this letter.

Your response to the above should be submitted with a copy of this letter to the Office of Submissions and Intellectual Property. In order to facilitate and ensure proper processing of your response, please include a revised Submission Certificate, quoting the product name, assigned dossier ID, and control number of the original submission, and address your response to:

Director, Office of Submissions and Intellectual Property
Therapeutic Products Directorate
Finance Building,
101 Tunney's Pasture Driveway
Address Locator 0201A1
Ottawa, Ontario, K1A 0K9

Attention: Office of Regulatory Affairs
Biologic and Radiopharmaceutical Drugs Directorate

Sincerely,

Celia Lourenco, Ph.D.
Director General