Qualifying Notice: Retevmo

Therapeutic Product Directorate
Holland Cross, Tower “B”
6th Floor, 1600 Scott Street
Address Locator #3106B
Ottawa, Ontario
K1A 0K9

Dossier ID: e233861

Loxo Oncology Inc.
[employee name removed]
[employee’s title removed]
281 Tessier Blvd,
Stamford, Connecticut, United States,
06901

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 Retevmo (selpercatinib), control number 243748, for the indications:

Retevmo (selpercatinib) is indicated as monotherapy for the treatment of

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:

  1. A letter, signed by the Chief Executive Officer or designated signing authority of Loxo Oncology Inc., 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, Loxo Oncology Inc. consents to the posting of this NOC/c-QN on Health Canada’s website once market authorization has been received.
  2. A Letter of Undertaking signed by the Chief Executive Officer or designated signing authority of Loxo Oncology Inc., having a form and content satisfactory to Health Canada, as indicated in NOC/c Guidance, including commitments to provide the following:

Confirmatory studies

  1. The final report of study [trial identifier removed].
    • To provide mature results in a sufficient number of adult patients and with a sufficient duration of follow-up to confirm the duration of response in adult patients with:
      • RET fusion-positive metastatic NSCLC
      • RET-mutant advanced or metastatic MTC
      • RET fusion-positive advanced or metastatic thyroid cancer
    • To provide mature results in a sufficient number of adolescent patients and with a sufficient duration of follow-up to confirm the duration of response in adolescent patients with advanced or metastatic RET-mutant MTC.
  2. The final report of study [trial identifier removed]
    • To provide substantial evidence for confirming that Retevmo is associated with an improved clinical benefit compared to currently marketed therapies in Canada for patients with metastatic RET fusion-positive NSCLC.
    • Based on the similarity of the underlying biology driving both RET fusion-positive thyroid cancers and RET fusion-positive NSCLC, the results from [trial identifier removed] in patients with RET fusion-positive NSCLC could provide data to support the clinical benefit of selpercatinib in patients with RET fusion-positive thyroid cancer.
  3. The final report of study [trial identifier removed]
    • To provide substantial evidence for confirming that Retevmo is associated with an improved clinical benefit compared to currently marketed therapies in Canada for patients with advanced or metastatic RET-mutant MTC. The results of the efficacy endpoints “progression-free survival” and “overall survival” will be used to confirm the improved clinical benefit. The primary endpoint “Treatment failure-free survival” is not considered to be sufficient for confirming the clinical effectiveness of selpercatinib.
    • To provide confirmatory results supporting the clinical benefit of Retevmo for the treatment of adolescent patients with advanced or metastatic RET-mutant MTC.
  4. The final report of study [trial identifier removed]
    • To support the clinical benefit of Retevmo for the treatment of adolescent patients with advanced or metastatic RET-mutant MTC.
  5. An integrated analysis of the clinical benefit of Retevmo in pediatric patients 12 years and older from [trial identifiers removed] that further characterizes the efficacy of Retevmo and its potential serious risk of long-term adverse effects of selpercatinib on growth and development.
  6. Annual progress reports of confirmatory trials.

Post market safety monitoring studies

  1. 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.
  2. 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.
  3. 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.
  1. A draft of the 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, as applicable), disclosing the nature of the authorization granted for Retevmo for the indications:

    Retevmo (selpercatinib) is indicated as monotherapy for the treatment of

    • metastatic RET fusion-positive non-small cell lung cancer (NSCLC) in adult patients,
    • RET-mutant medullary thyroid cancer (MTC) in adult and pediatric patients 12 years of age and older with unresectable advanced or metastatic disease,
    • RET fusion-positive differentiated thyroid carcinoma in adult patients with advanced or metastatic disease (not amenable to surgery or radioactive iodine therapy) following prior treatment with sorafenib and/or lenvatinib.
  2. 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 Retevmo for the indications:

    Retevmo (selpercatinib) is indicated as monotherapy for the treatment of

    • metastatic RET fusion-positive non-small cell lung cancer (NSCLC) in adult patients,
    • RET-mutant medullary thyroid cancer (MTC) in adult and pediatric patients 12 years of age and older with unresectable advanced or metastatic disease,
    • RET fusion-positive differentiated thyroid carcinoma in adult patients with advanced or metastatic disease (not amenable to surgery or radioactive iodine therapy) following prior treatment with sorafenib and/or lenvatinib.

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.

Your sincerely,

[employee name removed]
Director General
[employee name removed]

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