Qualifying Notice - Polivy

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

Dossier ID: HC6-024-e219417
Control #: 232303

[employee’s name removed]
[employee’s title removed]
Hoffmann-La Roche Limited
7070 Mississauga Road
Mississauga, ON  L5N 5M8
Fax: 905-542-5678

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 New Drug Submission (NDS) for Polivy (polatuzumab vedotin for injection), Control Number 232303, indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, who are not eligible for autologous stem cell transplant and have received at least one prior therapy 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 Hoffmann-La Roche Limited, 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, Hoffmann-La Roche Limited 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 Hoffmann-La Roche Limited, 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 (3-15):
  3. During review, the Sponsor committed to submitting the primary clinical study report for study GO29365. This included the primary analysis of both Arm G and Arm H. It is requested by BRDD that the Sponsor submit these results, as an S/NDS, if the study outcomes have any impact on the benefit/risk profile of Polivy.

Confirmatory Studies

  1. Submit, as an SNDS-c, the final report for the confirmatory study (GO39942) entitled: A phase 3, multicenter, randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of Polivy in combination with rituximab and CHP (R-CHP) versus rituximab and CHOP (R-CHOP) in previously untreated patients with diffuse large B-cell lymphoma. The estimated study enrollment is 875 patients and the primary endpoint of the study is progression-free survival (PFS). Key secondary endpoints of this study would include complete remission rate as assessed by an independent review committee and overall survival.
    1. The Sponsor should provide the approximate date of completion of the confirmatory study (GO39942) and should commit to an approximate date of filing the SNDS-c.
    2. The Sponsor should acknowledge that the indication for Polivy may be withdrawn if study GO39942 does not demonstrate that Polivy plus R-CHP is associated with a PFS that is both statistically significant and clinically meaningful over R-CHOP.

Progress Reports of Confirmatory Trials and Other Ongoing Trials

  1. In accordance with section 3.2 and Appendix 4 of the Guidance Document: Notice of Compliance with Conditions (NOC/c) the sponsor is required to submit on an annual basis status reports on the progress of ongoing confirmatory trials. This annual status report should be submitted within 60 calendar days of the market authorization anniversary or a date agreed upon at the time of the issuance of the market authorization.

Post-Marketing Safety Monitoring

  1. The MHPD recommendation to include pulmonary toxicity (including but not limited to pneumonitis) in the RMP as an important potential risk.
  2. Given the limitations of the clinical trial program (e.g., heterogeneous population, varying POLIVY dose/schedule, varying concomitant treatments and small clinical trial program), the MHPD recommends that the sponsor, in their PBRERs, provide an analysis of any new cases of:
    1. gastrointestinal complications (including but not limited to colitis and perforation)
    2. pancreatitis
    3. serious infections (including but not limited to reactivated viral and opportunistic infections)
  3. Routine pharmacovigilance activities - Should marketing authorization of POLIVY in Canada be granted, the sponsor is requested to provide a PBRER to Health Canada every 6 months; frequency will be re-evaluated once the first PBRER is reviewed by Health Canada. The PBRER should include Canadian exposure data.
  4. The sponsor must report must report all serious ARs that occurred in Canada and all serious unexpected ARs that occurred 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 this Letter of Undertaking, will be sent to the Biologic and Radiopharmacutical Drugs Directorate (BRDD).  Reporting will be conducted as per section 3.4.1 of the Guidance Document: Notice of Compliance with Conditions (NOC/c) and in accordance with current Food and Drug Regulations (C.01.016) 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. 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

  1. Receive pre-clearance by the Pharmaceutical Advertising Advisory Board (PAAB) for all promotional material related to products authorized under the NOC/c policy as per section 5.1 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
  2. Provide 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).
  3. Provide an up-to-date, complete listing of ongoing additional clinical trials related to Polivy, appended to the draft Letter of Undertaking, as per Section 4.5 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
  4. Submit to Health Canada any other analyses that have been designated as post-marketing commitments to other international authorization granting agencies as per section 3.4.4 of the Guidance for Industry, Notice of Compliance with Conditions (NOC/c).
  5. Provide copies of any marketing authorizations or other regulatory actions for Polivy 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

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