Qualifying notice for Qalsody (283158)

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

Dossier ID: e232868
Control number: 283158

Biogen Canada Inc.
[name of employee removed]
Manager, Regulatory Affairs
3250 Bloor Street West, East Tower, Suite 1200
Toronto ON M8X 2X9
Email: regulatory_canada@biogen.com

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 New Drug Submission for Qalsody (tofersen), Control Number 283158, qualifies to be considered for authorization in accordance with the above guidance document for the following indication: Treatment of adults with amyotrophic lateral sclerosis associated with a mutation in the superoxide dismutase 1 (SOD1) gene.

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 Biogen Canada Inc., 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), Biogen Canada Inc. 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 Biogen Canada Inc., 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. In order to verify the clinical benefit and further characterise the benefit-harm-uncertainty profile of Qalsody, complete Study 233AS303, "A Phase 3 Randomized, Placebo Controlled Trial With a Longitudinal Natural History Run-In and Open-Label Extension to Evaluate BIIB067 Initiated in Clinically Presymptomatic Adults With a Confirmed Superoxide Dismutase 1 Mutation". (Final study report for Study 233AS303 expected Q4 2028; study completion timeline is dependent on completion of enrollment for Part B).
2. To further investigate the long-term efficacy and safety of tofersen in the treatment of SOD1-ALS, submit the final Clinical Study Report (CSR) for the long-term extension study (Study 233AS102) and the summary of integrated analyses of Study 233AS101 and Study 233AS102 (Target: Q3 2025).

Progress reports of confirmatory trials

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 the Biogen Canada Inc. and Health Canada should 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 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).
5. Provision of Periodic Safety Update Reports or Periodic Benefit-Risk Evaluation Reports-C for NOC/c Products (PSUR-Cs or PBRER-Cs) for the first two-year period of marketing in Canada (referring to the market launch / market notification date not the Notice of Compliance (NOC) approval date).

   PSUR-Cs/PBRER-Cs should be prepared in accordance with the E2C(R1) and E3C(R2) ICH Guidelines, 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, annual summary reports (e.g. 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 profile.

6. 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

7. Receive pre-clearance by the Pharmaceutical Advertising Advisory Board (PAAB) for all promotional material related to Qalsody (tofersen), 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: https://www.canada.ca/en/health-canada/services/drugs-health-products/regulatory-requirements-advertising.html.
8. An up-to-date, complete listing of ongoing additional clinical trials related to Qalsody (tofersen), appended to the draft Letter of Undertaking, as per Section 4.5 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
9. Copies of any marketing authorizations for Qalsody (tofersen), from any other drug regulatory authority as per Section 4.6 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).

3. A draft of the Product Monograph that is consistent with the requirements in accordance with the Guidance Document: Product Monograph (2020) and the Product Monograph Master Template, disclosing the nature of the authorization granted for Qalsody (tofersen), and the need to conduct confirmatory trials.

4. A final mock-up of the Package Insert (if applicable), in line with the requirements outlined in Health Canada's Questions and Answers: Plain Language Labelling Regulations (Q&A: PLL) for Prescription Drugs - document, containing boxed text disclosing the nature of the authorization granted for Qalsody (tofersen), for the indication listed above.

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