Elrexfio for RRMM recommended in EU for conditional approval
Therapy won similar approval in US in August for hard-to-treat myeloma
A committee of the European Medicines Agency (EMA) has recommended that Elrexfio (elranatamab) — a therapy already in use in the U.S. — be conditionally approved for treating people in Europe with relapsed or refractory multiple myeloma (RRMM).
The recommendation, from the EMA’s Committee for Medicinal Products for Human Use (CHMP), specifically suggests that the Pfizer candidate be authorized on its own for multiple myeloma patients who have received at least three previous therapies and whose cancer has worsened since the most recent round of treatment. Elrexfio also is being tested in combination with other medications for use in patients with relapses or whose myeloma is hard to treat.
The CHMP’s opinion now will be reviewed by the European Commission, which has final say over approving medications in the European Union. The regulatory body isn’t required to abide by the CHMP’s recommendations, but it usually does.
Conditional approval of Elrexfio would allow the medication to be brought to market with less complete data than normally is needed for a full approval. The conditional approval pathway is designed to allow earlier access to treatments that fulfil an unmet medical need, and when such early availability is believed to outweigh potential risks.
Full approval would be dependent on complete results from the ongoing Phase 2 MagnetisMM-3 clinical trial (NCT04649359), whose top-line data supported the regulatory application, as well as further proof of the therapy’s safety and efficacy in a larger Phase 3 trial.
Committee recommends Elrexfio be given on its own, not in a combo
One trial expected to help meet that criteria is the ongoing Phase 3 MagnetisMM-5 (NCT05020236). It is designed to test Elrexfio — given on its own or in combination with Darzalex (daratumumab) — against the standard treatment combination of Darzalex, Pomalyst (pomalidomide), and dexamethasone. More than 850 RRMM patients have been enrolled.
If positive, MagnetisMM-5 results also will be used to support Elrexfio’s full approval in the U.S., where the therapy received conditional approval in August. Elrexfio also is being considered for approval by authorities in Japan.
The therapy had previously received orphan drug and PRIME designations in the EU, and orphan drug and fast track designations in the U.S. All are meant to accelerate a therapy’s clinical development and review process.
Elfrexio is an antibody-based medication that works by simultaneously binding to two protein targets: B-cell maturation antigen or BCMA, a protein found on myeloma cells, and CD3, a protein found on cancer-killing immune cells called T-cells. By binding to these two targets at the same time, the therapy aims to activate T-cells to eliminate myeloma cells.
The CHMP’s recommendation was based on data from the MagnetisMM-3 study, which also supported Elrexfio’s conditional approval in the U.S.
The trial’s pivotal part included 123 people with multiple myeloma who had failed to respond to at least three prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody. None of the patients had previously been given a treatment that targets BCMA.
The results showed that nearly two-thirds (61%) of patients responded to treatment, meaning their cancer burden was decreased, after more than a year of treatment with Elrexfio. Moreover, more than 1 in 3 (35%) achieved a complete response or better.
Among those who responded to treatment, more than 70% were likely to live without cancer progression for more than a year, on average.
Elrexfio can cause life-threatening side effects
Safety data from patients given Elrexfio within trials have shown that the most commonly reported side effects are decreased blood cell counts, infections, and cytokine release syndrome (CRS) — an inflammatory condition characterized by fever, vomiting, shortness of breath, headache and low blood pressure.
One of the main risks associated with Elrexfio is that it can cause immune effector cell-associated neurotoxicity (ICANS), a form of inflammatory brain damage that can be life-threatening. The CHMP’s recommendation for conditional approval of Elrexfio includes monitoring and mitigation strategies aiming to minimize the risks from CRS and ICANS for patients who would be given the treatment.
MagnetisMM-5 aims to enroll up to 854 adults with multiple myeloma who failed to adequately respond to at least one prior line of treatment, including Revlimid (lenalidomide) and a proteasome inhibitor. Patients, however, may not have more than three previous lines of therapy. The study, which is expected to run through 2026, may still be recruiting patients at hundreds of locations worldwide.