Pfizer Elrexfio bags USFDA accelerated nod for multiple myeloma treatment

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 (NCT04649359) showed meaningful responses among heavily pretreated RRMM patients 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 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 also includes 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.

“Most multiple myeloma patients will experience relapse or resistance of their disease to treatment, often facing increased symptom burden and lowering their chance of surviving longer with each attempted line of therapy,” said MagnetisMM clinical trial investigator Ajay Nooka, MD, MPH, Director of the Multiple Myeloma Program at Winship Cancer Institute of Emory University. “By offering durable clinical response with an established safety profile and the convenience of subcutaneous administration, ELREXFIO provides a much-needed new option for heavily pre-treated multiple myeloma patients who are struggling with relapsed myeloma.”

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 ≥20%) are CRS, 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%) 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, dexamethasone, and diphenhydramine pre-treatment, is intended to reduce the incidence and severity of CRS. 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 CRS and NT, 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. Data will be shared as available.