Qualifying notice for Akeega

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

Dossier ID: HC6-024-e254684
Control number: 265223

[employee name removed]
[employee title removed]
Janssen Inc.
19 Green Belt Drive
Toronto ON M3C 1L9
Fax number: 1-800-791-8047
[employee email address removed]

Dear [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 for Akeega (niraparib, abiraterone acetate), Control Number 265223, for the indication of The treatment of adult patients with deleterious or suspected deleterious BRCA mutated (germline and/or somatic) metastatic castration resistant prostate cancer (mCRPC), who are asymptomatic/mildly symptomatic, and in whom chemotherapy is not clinically indicated. Patients must have confirmation of BRCA mutation before Akeega treatment is initiated, qualifies to be considered for authorization 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 Guidance Document: Notice of Compliance with Conditions (NOC/c), including commitments to provide the following:

Confirmatory studies

1. To confirm the clinical benefit in the BRCA mutant subgroup, submit the final efficacy analysis (Clinical cut off May 2023) from the Phase 3 Magnitude study as a Supplemental New Drug Submission-Confirmatory (SNDS-C). The analyses should verify and describe the clinical benefit of niraparib plus abiraterone acetate and prednisone in terms of Overall Survival in the BRCA subgroup Cohort 1.

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 Janssen Inc. and Health Canada should be outlined in the Letter of Undertaking.

Safety monitoring

3. Provision of Periodic Benefit-Risk Evaluation Reports (PBRER-Cs) or Periodic Safety Update Reports (PSUR-Cs) in a manner deemed consistent with E2C ICH Guidelines, every six months for the initial two years of market authorization and on an annual basis thereafter until such time as all conditions for market authorization under the NOC/c Guidance have been removed. The PBRER-Cs or PSUR-Cs should include cumulative data on relevant unlisted Adverse Reactions (ARs) from the date of marketing to the time of the report.
4. Notification and reporting on specific issues of concern, as outlined in Section 3.4.4, Post-Market Commitments: Notification and Reporting of Specific Issues of Concern, of the Health Canada NOC/c Guidance.
5. Report(s) of all serious adverse drug reactions (ADRs) that occurred in Canada and all serious unexpected ADRs that occurred outside of Canada should be forwarded within 15 days to the Marketed Health Products Directorate, in accordance with the current Food and Drug Regulations (C.01.017) and guidance documents.

Additional information

6. Receive pre-clearance by the Pharmaceutical Advertising Advisory Board (PAAB) for all promotional material related to Akeega (niraparib, abiraterone acetate) 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.
7. An up-to-date, complete listing of ongoing additional clinical trials related to Akeega (niraparib, abiraterone acetate), 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 Akeega (niraparib, abiraterone acetate) from any other drug regulatory authority as per Section 4.6 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).

3. A final mock-up of the Package Insert (if applicable), in line with the requirements outlined in Health Canada's Guidance Document, Questions and Answers: Plain Language Labelling Regulations (Q&A: PLL), containing boxed text disclosing the nature of the authorization granted for Akeega for the indication of The treatment of adult patients with deleterious or suspected deleterious BRCA mutated (germline and/or somatic) metastatic castration resistant prostate cancer (mCRPC), who are asymptomatic/mildly symptomatic, and in whom chemotherapy is not clinically indicated.

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,
Karen Reynolds
Director General
Pharmaceutical Drugs Directorate
KR/oh