Qualifying notice for Braftovi (292474)

Pharmaceutical Drugs Directorate
Holland Cross, Tower "B"
6th Floor, 1600 Scott Street
Address Locator number 3106B
Ottawa ON  K1A 0K9

Dossier ID: e224354
Control number: 292474

[name of employee removed]
Manager, Regulatory Sciences
Pfizer Canada ULC
17300 Trans-Canada Highway
Kirkland QC  H9J 2M5
Fax No.: 15144266824
[email of employee removed]

Dear [name of employee removed]:

This Notice of Compliance with Conditions Qualifying Notice (NOC/c-QN), issued in accordance with the Health Canada Guidance Document: Notice of Compliance with Conditions (NOC/c), is to advise you that information submitted in support of the Supplemental New Drug Submission for Braftovi (encorafenib), control number 292474, qualifies to be considered for authorization in accordance with the above guidance document for the following indication:

Braftovi (encorafenib) is indicated, in combination with cetuximab and mFOLFOX6, for the treatment of patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, as detected by a validated test.

In keeping with the provisions outlined in the Guidance Document: Notice of Compliance with Conditions (NOC/c), the following additional information is requested to complete the assessment:

1. A letter, signed by the Chief Executive Officer or designated signing authority of Pfizer Canada ULC, indicating that you agree to have this submission considered under the Guidance Document: Notice of Compliance with Conditions (NOC/c). Please be reminded that in agreeing to accept a Notice of Compliance (NOC) under the Guidance Document: Notice of Compliance with Conditions (NOC/c), Pfizer Canada ULC consents to the posting of this NOC/c-QN on Health Canada's website once market authorization has been received.
2. A draft Letter of Undertaking signed by the Chief Executive Officer or designated signing authority of Pfizer Canada ULC, having a form and content satisfactory to Health Canada, as indicated in Guidance Document: Notice of Compliance with Conditions (NOC/c), including commitments to provide the following:

Confirmatory studies

1. Health Canada requests, as a Supplement to a New Drug Submission-Confirmatory (SNDS-c), the final report from the ongoing study entitled “C4221015: An Open Label, Multicentre, Randomized Phase 3 Study of First-Line Encorafenib Plus Cetuximab With or Without Chemotherapy Versus Standard of Care Therapy With a Safety Lead-In of Encorafenib and Cetuximab Plus Chemotherapy in Participants With Metastatic BRAF V600E-Mutant Colorectal Cancer (the Breakwater study). Complete clinical study reports (CSR) should permit confirmation of Objective Response Rate (ORR) in the Full Analysis Set (FAS) and contain reasonable estimates of Progression-Free Survival (PFS) and Overall Survival (OS) to confirm the safety and efficacy of the combination of encorafenib + cetuximab + mFOLFOX6 for the treatment of BRAF V600E-mutated metastatic colorectal cancer (mCRC).
   1. Pfizer Canada ULC should commit to an approximate date of filing of the SNDS-c.
   2. Pfizer Canada ULC should acknowledge that the indication authorized under the NOC/c pathway for Braftovi under Control No. 292474 can be withdrawn or revised if the aforementioned results do not confirm clinical benefit of encorafenib, in combination with cetuximab and mFOLFOX6, for the treatment of patients with mCRC with a BRAF V600E mutation.

Progress reports of confirmatory trials

2. 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 the Pfizer Canada ULC and Health Canada should be outlined in the Letter of Undertaking.

Safety monitoring

3. 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 reported 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).
4. Periodic Safety Update Reports or Periodic Benefit-Risk Evaluation Reports-C for NOC/c Products (PSUR-Cs or PBRER-Cs) on an annual basis until such time as conditions associated with the market authorisation are removed. PSUR-Cs/PBRER-Cs should be prepared in accordance with the E2C(R2)ICH Guideline, including format and content, as per section 3.4.2 of the Guidance Document: Notice of Compliance with Conditions (NOC/c). Please note that once all the commitments are fulfilled, Periodic Benefit-Risk Evaluation Reports-Pharmacovigilance (PBRER-PV) or Periodic Safety Update Reports-Pharmacovigilance (PSUR-PV) should be submitted as stipulated in the regulations (subsection C.01.018(4)), upon request or in situations where the Market Authorization Holder (MAH) identifies any negative safety findings and/or significant change in the product’s overall benefit-risk and safety profiles.
5. 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

6. Receive pre-clearance by the Pharmaceutical Advertising Advisory Board (PAAB) for all promotional material related to Braftovi (encorafenib) as per section 5.1 of the Guidance Document: Notice of Compliance with Conditions (NOC/c). For more information on the regulatory requirements for advertising, please visit: Regulatory Requirements for Advertising.
7. An up-to-date, complete listing of ongoing additional clinical trials related to Braftovi (encorafenib), appended to the draft Letter of Undertaking, as per Section 4.5 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
8. Copies of any marketing authorizations for Braftovi (encorafenib) 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 guidance documents on the Management of Drug Submissions and Applications and Notice of Compliance with Conditions (NOC/c), respectively.

Sponsors are instructed to submit a complete response (refer to Guidance Document: Notice of Compliance with Conditions (NOC/c)) with the requested information within 30 calendar days of the date of this letter directly to the Office of Submissions and Intellectual Property (OSIP) via the Common Electronic Submissions Gateway using Regulatory Enrolment Process.

In order to facilitate and ensure proper processing of your response, please quote the product name, assigned dossier ID and control number of the original submission.

Yours sincerely,

Kelly Robinson
Director General
Pharmaceutical Drugs Directorate