Qualifying notice for Jaypirca (293854)

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

Dossier ID: e286404
Control number: 293854

Eli Lilly Canada Inc.
c/o [name of employee removed]
Director, Regulatory Affairs
Exchange Tower
130 King Street West, Suite 900, PO Box 73
Toronto, Ontario M5X
Fax: 416 693-3547

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 New Drug Submission for Jaypirca (pirtobrutinib), Control Number 293854, qualifies to be considered for authorization in accordance with the above guidance document for the following indications:

Jaypirca (pirtobrutinib) is indicated as monotherapy for the treatment of adult patients with:

• mantle cell lymphoma (MCL) relapsed or refractory in patients who have previously received at least two lines of systemic therapy including a Bruton tyrosine kinase (BTK) inhibitor.
• chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy including a BTK inhibitor and a BCL-2 inhibitor.

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 Eli Lilly 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), Eli Lilly 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 Eli Lilly 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 study

1. To confirm the clinical benefit of Jaypirca (pirtobrutinib) in relapsed or refractory mantle cell lymphoma (MCL) patients who have previously received at least two lines of systemic therapy including a Bruton tyrosine kinase (BTK) inhibitor, please submit following study as a Supplemental New Drug Submission-Confirmatory (SNDS-C).
   Study LOXO-BTK-20019 (J2N-OX-JZNM): A Phase 3 Open-Label, Randomized Study of LOXO-305 Versus Investigator Choice of BTK Inhibitor in Patients With Previously Treated BTK Inhibitor Naïve Mantle Cell Lymphoma (BRUIN MCL-321).
2. To confirm the clinical benefit of Jaypirca (pirtobrutinib) in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy including a BTK inhibitor and a BCL-2 inhibitor, please submit following study as a Supplemental New Drug Submission-Confirmatory (SNDS-C).

Study LOXO-BTK-20020 (J2N-OX-JZNN): A Phase 3 Open-Label, Randomized Study of LOXO-305 versus Investigator’s Choice of Idelalisib plus Rituximab or Bendamustine plus Rituximab in BTK Inhibitor Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321).

Please, include an estimated primary analysis completion date in the Letter of Undertaking for both confirmatory trials.

Progress reports of confirmatory trials

3. 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 Eli Lilly Canada Inc. and Health Canada should be outlined in the Letter of Undertaking.

Safety monitoring

4. 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).
5. Periodic Safety Update Reports or Periodic Benefit-Risk Evaluation Reports-C for NOC/c Products (PSUR-Cs or PBRER-Cs) on an annual basis 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.
6. 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

7. Receive pre-clearance by the Pharmaceutical Advertising Advisory Board (PAAB) for all promotional material related to Jaypirca (pirtobrutinib) 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.
8. An up-to-date, complete listing of ongoing additional clinical trials related to Jaypirca (pirtobrutinib), appended to the draft Letter of Undertaking, as per Section 4.5 of the Guidance Document: Notice of Compliance with Conditions (NOC/c).
9. Copies of any marketing authorizations for Jaypirca (pirtobrutinib) 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 Questions and Answers: Plain Language Labelling Regulations (Q&A: PLL) for Prescription Drugs - document, containing boxed text disclosing the nature of the authorization granted for Jaypirca (pirtobrutinib) for the indication listed above.

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