Blincyto - Notice of Compliance with Conditions - Qualifying Notice

Biologics and Genetic Therapies Directorate
100 Eglantine Driveway
Address Locator #0601C
Ottawa, Ontario
K1A 0K9

Dossier ID: HC6-024-e176095
Control #: 210780

November 26, 2019

[Employee's name removed]
[Employee's title removed]
Amgen Canada Incorporated
6775 Financial Drive, Suite 100
Mississauga, ON  L5N 0A4
Fax: 866-578-8811

Dear [Employee's 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 Supplemental New Drug Submission (SNDS) for BLINCYTO (blinatumomab), Control Number 210780, indicated for the treatment of patients with Philadelphia chromosome-negative CD19 positive B-precursor acute lymphoblastic leukemia (ALL) in first or second hematologic complete remission with minimal residual disease (MRD) greater than or equal to 0.1%, 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 Amgen Canada Incorporated, 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, Amgen Canada Incorporated consents to the posting of the NOC/c-QN on Health Canada's website.
  2. A draft Letter of Undertaking signed by the Chief Executive Officer, or designated signing authority, of Amgen Canada Incorporated, 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. Submit as an SNDS-C, the final report for Study E1910, conducted by the Eastern Cooperative Oncology Group (ECOG), a phase 3, randomized, controlled study to assess the effect of blinatumomab in combination with induction chemotherapy compared with induction chemotherapy alone in adult subjects with newly diagnosed Philadelphia chromosome negative B cell ALL. Although this study will not provide evidence for the surrogacy of MRD-negativity for OS and RFS, the data from 2.5 years of follow-up are expected to characterize the survival outcomes of MRD-positive patients who convert to MRD-negative following treatment with blinatumomab in comparison to MRD-negative patients randomized to SOC chemotherapy.
  2. Submit as an SNDS-C, the final report for Study AALL1331, conducted by the Children’s Oncology Group (COG), which is a Phase 3, randomized, controlled, risk-stratified, multicentre study to assess efficacy and safety of blinatumomab compared with standard combination chemotherapy in treating subjects (≥ 1 to < 31 years of age) with B cell ALL who are in first relapse. This study is expected to provide data on survival by MRD-negativity status. As patients in this study will be followed for 10 years, it is expected that the follow-up data will allow for adequate assessment of OS and survival after HSCT.

The sponsor should acknowledge that they are aware that the MRD-positive indication for BLINCYTO can be withdrawn if the results from the confirmatory studies, E1910A and ALL1331, fails to demonstrate that the overall risk/benefit assessment is favorable as determined by the Biologics and Genetic Therapies Directorate (BGTD).

  1. Submit along with the final reports of the confirmatory studies, the report of the final analysis of Study MT103-203, which was planned to be conducted 5 years after the last subject enrolled into the study.

 Progress Reports of Confirmatory Trials and Other Ongoing Trials

  1. 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 Amgen Canada Incorporated and Health Canada must be outlined in the Letter of Undertaking. These reports should be included in the PBRER.
  2. Submit to Health Canada any other analyses that have been designated as post-marketing commitments to other international authorities.

Safety Monitoring

  1. 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 Biologics and Genetic Therapies 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).
  2. Submit the Periodic Benefit-Risk Evaluation Reports-C for NOC/c Products (PBRER-Cs) on an annual basis until such time as conditions associated with the market authorisation are removed. Include, in each PBRER, an analysis of all Adverse Events as per the Pharmacovigilance Plan as well as safety updates from all ongoing and future clinical trials with BLINCYTO. 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).
  3. 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).

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
Biologics and Genetic Therapies Directorate

Sincerely,

Celia Lourenco, Ph.D.
Director General

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