Regulatory Decision Summary for Elrexfio

The submission was filed seeking a notice of compliance with conditions for Elrexfio for use in the treatment of relapsed or refractory multiple myeloma patients who have previously received drugs from each of three commonly drug classes, including immunomodulatory imide drugs (IMiD), proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies (anti-CD38 mAb).

The product was authorized with conditions for the following indication:

Elrexfio (elranatamab injection) is a B-cell maturation antigen (BCMA)-directed and CD3‑directed bispecific antibody 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 who have demonstrated disease progression on the last therapy.

Authorization was based on a single pivotal phase 2, single-arm, multi-center study titled MagnetisMM-3 with support from 3 studies designed to investigate safety and pharmacology. Patients (n = 123) with relapsed or refractory multiple myeloma (RRMM) who were previously treated with prior lines of therapy that, when considered together, included at least one IMiD, one PI and one anti-CD38 mAb, received subcutaneous elranatamab monotherapy via a step-up dosing regimen.

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. The ORR was 61.0% with 27.6% of patients achieving a complete response (CR) or better. The median duration of response (DOR) was not reached at the time of data cut-off. The observed ORR is supported by the durability of the response. These results are considered promising evidence of clinical benefit. The benefit of Elrexfio, 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 is required to be submitted as a commitment to the Notice of Compliance with conditions.

The safety of Elrexfio was evaluated in 187 adult patients with RRMM. The most commonly reported adverse events (≥30%) were: cytokine release syndrome (CRS), anemia, fatigue, neutropenia, injection site reaction, diarrhea, upper respiratory tract infection, thrombocytopenia, and pneumonia. Serious adverse reactions, including CRS, neurologic toxicities (including Immune Effector Cell-Associated Neurotoxicity Syndrome [ICANS]), infections, hepatitis B reactivation and hepatotoxicity, were reported. These safety findings and the applicable risk mitigation measures are described in the final Elrexfio Product Monograph (PM).

Overall, based on the evidence reviewed, the anticipated benefit outweighs the potential risks for Elrexfio 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 who have demonstrated disease progression on the last therapy.

Elrexfio is administered via subcutaneous injection. In line with the pivotal study, the recommended dosing regimen includes step-up dosing (12 mg on Day 1; 32 mg on Day 4), followed by weekly dosing (76 mg) beginning on Day 1 of week 2 and continued to week 23. It is recommended that responders switch to once every 2-week dosing (76 mg) at week 24. Dosing may continue until disease progression or unacceptable toxicity.

Health Canada granted this submission advanced consideration in accordance with the Notice of Compliance with Conditions (NOC/c) policy.

A Risk Management Plan (RMP) for Elrexfio was reviewed by Health Canada and considered acceptable.

The chemistry and manufacturing information submitted for Elrexfio 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 further details, please refer to the PM, approved by Health Canada and available through the Drug Product Database.