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Elrexfio based on Elranatamab for patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy. FDA accelerated approval


The U.S. Food and Drug Administration ( FDA ) has granted accelerated approval to Elrexfio ( Elranatamab-bcmm; Elranatamab ) for the treatment of adult patients with relapsed or refractory multiple myeloma ( RRMM ) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Approval was based on the results of the single-arm phase 2 MagnetisMM-3 trial, and continued approval for this indication is contingent upon verification of clinical benefit in a confirmatory trial(s).

Elrexfio is a subcutaneously delivered B-cell maturation antigen ( BCMA )-CD3-directed bispecific antibody ( BsAb ) immunotherapy that binds to BCMA on myeloma cells and CD3 on T-cells, bringing them together and activating the T-cells to kill myeloma cells.

The approval of Elrexfio is based on data from response rates and duration of response. Data from cohort A ( n=123 ) of the phase 2 MagnetisMM-3 study have shown meaningful responses among heavily pretreated patients with relapsed or refractory multiple myeloma who received Elrexfio as their first BCMA-directed therapy.
Among the patients in this study who received four or more lines of therapy prior to Elrexfio ( n=97 ), the overall response rate was 58%, with an estimated 82% maintaining the response for at least nine months.
The median time to first response was 1.2 months.

This study has also established Elrexfio as the first BCMA-directed therapy in the U.S. with once-every-other-week dosing for responding patients after 24 weeks of weekly therapy, which means less time at the clinic and potentially greater long-term treatment tolerability.

The label has also included data from MagnetisMM-3 cohort B ( n=64 ). Among the 63 patients in this cohort who received at least four prior lines of therapy, including a BCMA-directed therapy ( CAR-T or antibody-drug conjugate ), the overall response rate was 33% after a median follow-up of 10.2 months, with an estimated 84% maintaining the response for at least nine months.

In longer-term efficacy data for cohort A ( n=123 ) presented at the 2023 European Hematology Association meeting, the objective response rate was 61%, and median duration of response, overall survival, and progression-free survival had not yet been reached at 14.7 months median follow-up. For the responding patients, the probability of maintaining a response at 15 months was 72%. Among responding patients who switched to every-other-week dosing at least six months prior to the data cut-off date ( n=50 ), 80% maintained or improved their response after the switch, with 38% attaining a complete response or better after the switch.

Elrexfio’s label contains a Boxed Warning for cytokine release syndrome ( CRS ) and neurologic toxicity ( NT ), including immune effector cell-associated neurotoxicity syndrome ( ICANS ), in addition to warnings and precautions for infections, neutropenia, hepatotoxicity and embryo-fetal toxicity.
The most common adverse reactions to Elrexfio ( incidence greater than or equal to 20% ) are cytokine release syndrome, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and fever ( pyrexia ).
The most common grade 3 to 4 laboratory abnormalities ( 20% or more ) are decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets. The step-up dose regimen ( 12/32/76 mg ), combined with Acetaminophen ( Paracetamol ), Dexamethasone, and Diphenhydramine pre-treatment, is intended to reduce the incidence and severity of cytokine release syndrome. As a precaution, patients should be hospitalized for 48 hours following the first step-up dose and for 24 hours following the second step-up dose. No hospitalization is required for the third step-up dose.

Given the risk of cytokine release syndrome and neurologic toxicity, including ICANS, Elrexfio is available only through a restricted program called the Elrexfio Risk Evaluation and Mitigation Strategy ( REMS ).

A confirmatory trial ( MagnetisMM-5 ) in the double-class exposed relapsed or refractory population involving 854 patients was initiated in 2022 to gather additional safety and efficacy data.

Multiple myeloma is an aggressive and currently incurable blood cancer that affects plasma cells made in the bone marrow. Healthy plasma cells make antibodies that help the body fight infection.
Multiple myeloma is the second most common type of blood cancer, with over 35,000 new cases of multiple myeloma diagnosed annually in the U.S. and 176,000 globally. About half of those diagnosed with multiple myeloma won’t survive beyond five years, and most will receive four or more lines of therapy due to relapse.
While disease trajectory varies for each person, relapses are nearly inevitable.
Real-world evidence has shown that people with multiple myeloma often become resistant to the three main classes of treatment ( proteasome inhibitors, immunomodulatory agents and anti-CD38 monoclonal antibodies ) after just a few rounds of therapy, and re-treating with these classes was common.
The goal of therapy for people with relapsed or refractory multiple myeloma is to achieve disease control with acceptable toxicity and improved quality of life. ( Xagena )

Source: Pfizer, 2023

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