Qualifying notice for Tagrisso (288417)

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

Dossier ID: e182735
Control number: 288417

AstraZeneca Canada Inc
c/o [name of employee removed]
Regulatory Affairs Project Manager
1004 Middlegate Road, Suite 5000
Mississauga ON L4Y 1M4
Fax: (905) 275-6271

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 Tagrisso, Control Number 288417, qualifies to be considered for authorization in accordance with the above guidance document for the following indication:

Unresectable Stage III

Tagrisso is indicated for the treatment of patients with locally advanced, unresectable (stage III) NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations (either alone or in combination with other EGFR mutations) and whose disease has not progressed during or following platinum based chemoradiation therapy.

• A validated test is required to identify EGFR mutation-positive status prior to treatment (see 7 Warnings and precautions, Assessment of EGFR Mutation Status).
• Marketing authorization with conditions was based on the primary efficacy endpoint of progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in subsequent analyses (see 14 Clinical trials).

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 AstraZeneca 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), AstraZeneca 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 AstraZeneca 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. The final clinical study report for the pivotal Study D5160C00048: A Phase III, Randomised, Double-Blind, Placebo-Controlled, Multicentre, International Study of Osimertinib as Maintenance Therapy in Patients with Locally Advanced, Unresectable EGFR Mutation-Positive Non-Small Cell Lung Cancer (Stage III) Whose Disease Has Not Progressed Following Definitive Platinum-Based Chemoradiation Therapy (LAURA).

   The results of the final analysis of OS (at approximately 60% maturity) will be used to confirm the clinical benefit of TAGRISSO observed in the primary analysis of the primary endpoint, PFS, for the ITT target population. The final OS analysis is event-driven and currently expected to occur in the first half of 2027 while the final report (including the final OS analysis) is expected to be available for submission as a Supplemental New Drug Submission-Confirmatory (SNDS-C) in the second half of 2027.

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 AstraZeneca Canada Inc. 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) covering the period of November 2023 to November 2026 and every 3 years 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(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 Tagrisso (osimertinib mesylate) 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 Tagrisso (osimertinib), 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 TAGRISSO (osimertinib mesylate) 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