Pfizer has achieved U.S. FDA accelerated approval for Elrexfio (elranatamab) in the context of relapsed or refractory multiple myeloma. This milestone stems from the Phase 2 MagnetisMM-3 study, which showcased meaningful response rates and response durations. Elrexfio, the first off-the-shelf fixed-dose subcutaneous BCMA-directed agent in the U.S., introduces the option of every-other-week long-term dosing after 24 weeks of weekly treatment. Pfizer is further driving the MagnetisMM clinical initiative to extend Elrexfio's reach to earlier treatment stages, encompassing monotherapy and combination applications with established or innovative therapies.
Pfizer has announced the U.S. Food and Drug Administration (FDA) granting accelerated approval for Elrexfio (elranatamab) for treating adult patients with relapsed or refractory multiple myeloma (RRMM), who have undergone at least four prior lines of therapy, inclusive of a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. This approval is grounded in outcomes from the single-arm Phase 2 MagnetisMM-3 trial. Continued approval is subject to confirming clinical benefits in forthcoming confirmatory trials. Elrexfio is a subcutaneous B-cell maturation antigen (BCMA)-CD3-directed bispecific antibody (BsAb) immunotherapy. It engages BCMA on myeloma cells and CD3 on T-cells, facilitating their interaction and activating T-cells to eliminate myeloma cells.
The foundation for Elrexfio's approval is established on response rates and response duration data. Results from Phase 2 MagnetisMM-3 study cohort A (n=123) demonstrated substantial responses among heavily treated RRMM patients using Elrexfio as their initial BCMA-directed therapy. Among patients who received four or more prior therapies prior to Elrexfio (n=97), the overall response rate was 58%, with around 82% sustaining the response for a minimum of nine months. The median time to the initial response was 1.2 months. Notably, this study established Elrexfio as the inaugural BCMA-directed therapy in the U.S. to offer once-every-other-week dosing for responsive patients following 24 weeks of weekly therapy. This feature translates to reduced clinic visits and potentially enhanced long-term treatment tolerance. The label also includes information from MagnetisMM-3 cohort B (n=64), wherein the overall response rate among 63 patients who had undergone at least four previous therapies, including a BCMA-directed therapy (CAR-T or antibody-drug conjugate), was 33% following a median follow-up of 10.2 months, with approximately 84% maintaining the response for at least nine months.
In the context of cohort A (n=123), longer-term efficacy data unveiled at the 2023 European Hematology Association meeting revealed an objective response rate of 61%, with the median duration of response, overall survival, and progression-free survival yet to be determined after 14.7 months median follow-up. The probability of maintaining a response at 15 months stood at 72% for responding patients. Within the subset of responding patients who transitioned to every-other-week dosing at least six months before the data cutoff date (n=50), 80% upheld or improved their response following the switch, with 38% achieving complete response or better outcomes.
Elrexfio's label encompasses a Boxed Warning for cytokine release syndrome (CRS) and neurologic toxicity (NT), including immune effector cell-associated neurotoxicity syndrome (ICANS). The label also highlights alerts and precautions concerning infections, neutropenia, hepatotoxicity, and embryo-fetal toxicity.
The common adverse reactions to Elrexfio (incidence ≥20%) include CRS, fatigue, injection site reactions, diarrhea, upper respiratory tract infections, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and fever (pyrexia).