Qualifying notice for Tecvayli

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

Dossier ID: HC6-024-e260336
Control number: 269369

[Employee name removed]
[Employee title removed]
Janssen Inc.
19 Green Belt Drive
Toronto ON M3C 1L9
[Employee email removed]

[Employee name 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 (NDS) for Tecvayli (teclistamab), control number 269369, indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy, qualifies to be considered for authorisation in accordance with the above guidance document. 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 Janssen 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), Janssen 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 Janssen 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 clinical study report (CSR) of [study name/number has been removed], a study of teclistamab in combination with daratumumab subcutaneously (SC) (Tec-Dara) versus daratumumab SC, pomalidomide, and dexamethasone (DPd) or daratumumab SC, bortezomib, and dexamethasone (DVd) in participants with relapsed or refractory multiple myeloma. The report should contain results from the primary analysis of Progression-free survival (PFS), and results from an analysis of overall survival (OS) that permits a meaningful evaluation of the OS benefit of teclistamab-based therapy versus the control treatment. The timelines should be included in the Letter of Undertaking (LOU), including the earliest anticipated availability of the data to be filed as a Supplement to a New Drug Submission (SNDS)-confirmatory (SNDS-c).

Additional commitment

2. The CSR of the final analysis of ongoing [study name/number has been removed], a Phase 1/2, first-in- human, open-label, dose escalation study of teclistamab, a humanized BCMA x CD3 bispecific antibody, in subjects with relapsed or refractory multiple myeloma, to further characterize the efficacy of Tecvayli in this patient population, including but not limited to in patients in Cohort A, Cohort C and those who met the protocol defined criteria and received less frequent dose of teclistamab. The timelines should be included in the LOU, including the earliest anticipated availability of the data to be filed as a SNDS-c.

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 Janssen 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 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. 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 until such time as conditions associated with the market authorisation are removed. 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). 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.
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 Tecvayli (teclistamab) 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 Tecvayli (teclistamab), 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 Tecvayli (teclistamab) 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 (CESG) using Regulatory Enrolment Process (REP).

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.

Sincerely,

Sophie Sommerer
Acting Director General