Qualifying notice for Leqembi (273840)
Biologic and Radiopharmaceutical Drugs Directorate
100 Eglantine Driveway
LCDC Building
Tunney's Pasture, A.L. 0601C
Ottawa ON K1A 0K9
Dossier ID: e265497
Control number: 273840
[employee name removed]
[employee title removed]
Eisai Limited
6925 Century Avenue, Suite 701
Mississauga, ON L5N 7K2
[employee email 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 (NDS) for Leqembi (lecanemab), Control Number 273840, qualifies to be considered for authorization in accordance with the above guidance document for the following indication: Leqembi (lecanemab for injection) is indicated for the treatment of adult patients with a clinical diagnosis of mild cognitive impairment or mild dementia due to Alzheimer's disease (early Alzheimer's disease), who are apolipoprotein E ε4 (ApoE ε4) noncarriers or heterozygotes, and who have confirmed amyloid pathology. 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:
- A letter, signed by the Chief Executive Officer, or designated signing authority of Eisai Limited, 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), Eisai Limited consents to the posting of this NOC/c-QN on Health Canada's website once market authorization has been received.
- A draft Letter of Undertaking signed by the Chief Executive Officer or designated signing authority of Eisai 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:
Confirmatory studies
Submit as an SNDS-c, the final study report for the Study 507 (BAN2401-G000-507): A Post-marketing study to confirm treatment benefit and fulfill conditions associated with market authorization in Canada for Leqembi (lecanemab) administered in adult patients with a clinical diagnosis of mild cognitive impairment or mild dementia due to Alzheimer's disease (early Alzheimer's disease), who are apolipoprotein E ε4 (ApoE ε4) noncarriers or heterozygotes, and who have confirmed amyloid pathology.
Longitudinal clinical assessment data will be captured from participants treated with Leqembi in real-world clinical practice. Participant data will be collected over a period of 18 months, starting at baseline and completing after 18 months after initiation of Leqembi treatment. The efficacy of Leqembi in patients with early AD as indicated per the Canadian Product Monograph (non-carriers and heterozygotes; indicated population) will be compared with placebo (PBO)-treated subjects from Study 301 Core on change from baseline in the CDR-SB score at 18 months of treatment (primary endpoint). Time to progression to the next stage of AD assessed by global CDR score by 18 months will also be included as a secondary endpoint.
Agreement was reached on the study protocol submitted in the docubridge version 0046 in the response to the request for clarification dated June 20, 2025. BRDD acknowledges that the study period is approximately 5 years (from August 2025 through August 2030). The sponsor should provide the estimated date of completion of Study 507 (BAN2401-G000-507), and should commit to provide an approximate date for filing their SNDS-c submission.
The sponsor should also acknowledge that the indication authorized under the NOC/c pathway for Leqembi (lecanemab) under control number 273840 can be withdrawn or revised, pending the outcome of Study 507. The decision by BRDD to remove the condition and/or modify the currently proposed indication will depend on the confirmation of clinical outcome benefit (i.e. changes in disease progression as assessed by CDR-SB score) in Study 507, and the demonstration of an overall favourable benefit-risk profile, upon review of the requested additional evidence.
Progress reports of confirmatory trials
- 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 Eisai Limited and Health Canada must be outlined in the Letter of Undertaking.
Safety monitoring
- 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).
- 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 first year. The frequency of subsequent PBRER submissions will be determined following the review of the second PBRER. PBRERs will be required until such time as conditions associated with the market authorization 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.
- 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
- Receive pre-clearance by the Pharmaceutical Advertising Advisory Board (PAAB) for all promotional material related to Leqembi (lecanemab) 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.
- An up-to-date, complete listing of ongoing additional clinical trials related to Leqembi (lecanemab), appended to the draft Letter of Undertaking, as per Section 4.5 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
- Copies of any marketing authorizations for Leqembi (lecanemab) 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
Director General