Regulatory Decision Summary for Talvey

The submission was filed seeking a notice of compliance with conditions for Talvey for use in the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

The product was authorized with conditions for the following indication:

Talvey (talquetamab injection) is indicated for:

The treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody, and have demonstrated disease progression on or after the last therapy.

Authorization was based on the combined non-clinical and clinical information. A single pivotal phase 1/2, first-in-human, open-label, dose escalation and expansion study was filed to support the efficacy and safety of talquetamab. Patients with relapsed or refractory multiple myeloma (RRMM) who were previously treated with prior lines of therapy that, when considered together, included at least one immunomodulatory drug (IMiD), one protease inhibitor (PI) and one anti-CD38 monoclonal antibody (mAb), received subcutaneous talquetamab monotherapy via a step-up dosing regimen and were evaluable for efficacy.

The primary efficacy outcome was the objective response rate (ORR) as determined by a Blinded Independent Review Committee (BIRC) assessment. The BICR applied the International Myeloma Working Group response criteria in assessing response. For patients dosed once weekly, the ORR was 74.1% with 33.6% of patients achieving a complete response (CR) or better. The median duration of response (DOR) was 9.5 months. For patients dosed once every two weeks, the ORR was 71.7% with 38.7% of patients achieving a CR or better. The median duration of response was not estimable at the time of the data cut-off. These results are considered promising evidence of clinical benefit. The benefit of Talvey, in terms of progression free survival or overall survival, has not been established and is to be evaluated in an ongoing Phase 3 clinical trial, which the sponsor has committed to submit to Health Canada as a condition of the authorization in accordance with the Notice of Compliance with Conditions policy.

The most important risks associated with Talvey are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS and ICANS, while predominantly low grade, have the potential to be life-threatening and are noted in a boxed warning within the product monograph. Other significant risks include oral toxicities, skin and nail toxicities, neurotoxicities (other than ICANS), hepatotoxicity and susceptibility to infection. The most commonly reported adverse events that were experienced by greater than 30% of trial participants were CRS, hypogammaglobulinemia, dysgeusia, nail disorder, musculoskeletal pain, anemia, weight decreased, dry mouth, pyrexia, skin disorder, rash, and xerosis. Additional safety findings and the applicable risk mitigation measures are described in the Talvey Product Monograph (PM).

Overall, based on the evidence reviewed, the anticipated benefit outweighs the potential risks of Talvey for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least three prior lines of therapy, including a PI, an IMiD agent and an anti-CD38 antibody, and have demonstrated disease progression on or after the last therapy.

Talvey is administered via subcutaneous injection. In line with the pivotal study, two recommended dosing regimens are included in the product monograph. Both include step-up dosing regimens, followed by weekly dosing (0.4 mg/kg) or dosing once every two weeks (0.8 mg/kg). Dose frequency may be reduced in order to manage certain toxicities. Dosing may continue until disease progression or unacceptable toxicity.

An updated Risk Management Plan (RMP) for Talvey was reviewed by Health Canada and considered acceptable.

The chemistry and manufacturing information submitted for Talvey has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

For more information on the conditions issued, please refer to the Notice of Compliance with conditions (NOC/c) Website.

For further details about Talvey, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.