Qualifying notice for Epkinly

Biologic and Radiopharmaceutical Drugs Directorate
100 Eglantine Driveway LCDC Building
Tunney's Pasture, A.L. 0601C
Ottawa ON K1A 0K9

Dossier ID: HC6-024-e262796
Control number: 271331

(Employee's name removed)
(Employee's title removed)
AbbVie Corporation
8401 Trans-Canada Highway
Saint-Laurent, Quebec
Canada H4S 1Z1
Email: employee's email removed

Dear (employee's 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 Epkinly (epcoritamab), Control Number 271331, qualifies to be considered for authorization in accordance with the above guidance document for the following indication: The treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, DLBCL transformed from indolent lymphoma, high grade B-cell lymphoma (HGBCL), primary mediastinal B- cell lymphoma (PMBCL) or follicular lymphoma Grade 3B (FLG3b) after two or more lines of systemic therapy and who have previously received or are unable to receive CAR-T cell therapy. 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 Abbvie Corporation, 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), Abbvie Corporation 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 Abbvie Corporation, 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

1. The sponsor should commit to the submission of a clinical trial for the purposes of providing confirmatory evidence of efficacy in the setting of relapsed/refractory diffuse large B-cell lymphoma. Specifically, the primary analyses of Study GCT3013-05: A Randomized, Open-Label, Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma should be submitted to Health Canada as an SNDS-C.

   Of note, the primary efficacy objective of the phase III study is to demonstrate that Epkinly monotherapy improves the overall survival of DLBCL patients compared to investigator's choice of either bendamustine plus rituximab (BR) or the combination of rituximab, gemcitabine, and oxaliplatin (R-GemOx). The sponsor should acknowledge that authorization may be revoked if the trial fails to show an overall survival benefit for Epkinly over investigator's choice of therapy. The sponsor should provide an estimated date of completion of the primary analyses for the study as well as an estimated date for the submission of the study to Health Canada.

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 Abbvie Corporation and Health Canada must 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) on a semi-annual basis for the first two (2) years then annually for an additional two (2) years. PSUR-Cs/PBRER-Cs should be prepared in accordance with the E2C(R1) and E3C(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 Epkinly (epcoritamab) 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.
7. An up-to-date, complete listing of ongoing additional clinical trials related to Epkinly (epcoritamab), 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 Epkinly (epcoritamab) 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 Epkinly (epcoritamab) 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 (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