Notice of Compliance with Conditions - Qualifying Notice for Lenvima
Therapeutic Product Directorate
Holland Cross, Tower "B"
6th Floor, 1600 Scott Street
Address Locator #3106B
Dossier ID: E176472
[employee name removed]
[employee title removed]
6925 Century Avenue, Suite 701
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 Supplemental New Drug Submission for LENVIMA (lenvatinib mesylate), control number 228723, for the indication “in combination with pembrolizumab, for the treatment of adult patients with advanced endometrial carcinoma that is not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior platinum-based systemic therapy, and are not candidates for curative surgery or radiation”, qualifies to be considered for authorization in accordance with the NOC/c Guidance. In keeping with the provisions outlined in the NOC/c Guidance, 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 NOC/c Guidance. Please be reminded that in agreeing to accept a Notice of Compliance (NOC) under the NOC/c Guidance, Eisai Limited consents to the posting of this NOC/c-QN on Health Canada's website once market authorization has been received.
- A 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 NOC/c Guidance, including commitments to provide the following:
Submit, as an SNDS-c, the final report for the confirmatory study titled: A multi-center, open-label, randomized, phase 3 trial to compare the efficacy and safety of lenvatinib in combination with pembrolizumab versus treatment of physician’s choice in participants with advanced endometrial cancer (Study [study number removed]). This study is designed to evaluate the effect of pembrolizumab + lenvatinib on progression free survival (PFS) and overall survival (OS) when compared to chemotherapy (investigator’s choice of doxorubicin or paclitaxel). The study is expected to enroll [number removed] patients [study type removed] with advanced, recurrent or metastatic endometrial carcinoma who have had disease progression after one prior platinum-based chemotherapeutic regimen.
- The Eisai Limited should provide the approximate date of completion of the confirmatory study and should commit to an approximate date of filing of the SNDS-c.
- The Eisai Limited should acknowledge that the indication authorized under the NOC/c pathway for LENVIMA under control # 228723 can be withdrawn or revised if Study [study number removed] does not demonstrate an improvement in efficacy, compared to chemotherapy, that is both statistically and clinically significant.
- Provision of annual Periodic Benefit-Risk Evaluation Reports (PBRER-Cs) or Periodic Safety Update Reports (PSUR-Cs) in a manner deemed consistent with E2C ICH Guidelines, until such time as all conditions for market authorization under the NOC/c Guidance have been removed. The annual 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.
- 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.
- 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.
- Receive pre-clearance by the Pharmaceutical Advertising Advisory Board (PAAB) for all promotional material related to LENVIMA (lenvatinib) authorized under the NOC/c policy as per section 5.1 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
- An outline of the agreed-upon advertising, labelling or distribution requirements imposed on the product, 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).
- An up-to-date, complete listing of ongoing additional clinical trials related to LENVIMA (lenvatinib), 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 LENVIMA (lenvatinib) from any other major drug regulatory authority (FDA, EMA, and TGA), if available, as per Section 4.6 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
- A draft of the English Product Monograph (PM) that is consistent with the requirements outlined in section 5.2.1 of the Guidance Document: Notice of Compliance with Conditions (NOC/c). Please note that boxed text should appear on the cover page as well as at the beginning of each major section of the Product Monograph (Parts I, II and III), disclosing the nature of the authorization granted for LENVIMA for the indication of “LENVIMA, in combination with pembrolizumab, is indicated for the treatment of adult patients with advanced endometrial carcinoma that is not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior platinum-based systemic therapy, and are not candidates for curative surgery or radiation. The indication is authorized based on tumour response rate and durability of response. An improvement in survival or disease-related symptoms has not been established (see CLINICAL TRIALS).”
- A final mock-up of the English Package Insert, 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 LENVIMA, for the indication of “LENVIMA is used with another medicine called pembrolizumab to treat adults with cancer of the endometrium (lining of the uterus) that has worsened after anti-cancer treatment that contained platinum; cannot be cured by surgery or radiation; is not microsatellite instability high (MSI-H); or is not mismatch repair deficient (dMMR)”.
Progress Reports of Confirmatory Trials and Other Ongoing 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 Eisai Limited and Health Canada must be outlined in the Letter of Undertaking.
Post Market Safety Monitoring
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. 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.
In order to facilitate and to ensure proper processing, please include a revised Submission Certificate with your response, quote the product name and control number, and address all correspondence to the Office of Submissions and Intellectual Property, Therapeutic Products Directorate, Health Canada, Finance Building, 101 Tunney’s Pasture Driveway, Address Locator 0201A1, Ottawa, Ontario, K1A 0K9.
Dr. J. Patrick Stewart, MD, CCFP(EM)
Therapeutic Products Directorate
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