Elranatamab, now Elrexfio, approved for hard-to-treat myeloma
Treatment for rare blood cancer approved by FDA in under 5 years
The U.S. Food and Drug Administration (FDA) has granted conditional approval to Pfizer‘s elranatamab — an antibody therapy to be marketed under the brand name Elrexfio — for adults with difficult-to-treat multiple myeloma.
Eligible patients will have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.
Patients prescribed Elrexfio can receive personalized support through Pfizer’s Oncology Together program, which offers help with insurance coverage navigation, among other services.
“We advanced this therapy from a first-in-patient trial to approval in less than five years, because we know that time is life for people living with multiple myeloma,” Angela Hwang, chief commercial officer and president of global biopharmaceuticals business at Pfizer, said in a company press release.
“We believe Elrexfio is poised to potentially become the new standard of care for multiple myeloma,” Hwang added.
Elrexfio part of global Project Orbis for advancing cancer treatments
The FDA’s decision comes about six months after the regulatory agency granted priority review to an application by Pfizer seeking the therapy’s approval. That application was accepted for Project Orbis, an international framework that allows concurrent submission and review of cancer therapies among project partners. Five other countries, namely Australia, Brazil, Canada, Singapore, and Switzerland, are participating.
The treatment also is under regulatory review in the European Union and Japan.
Elrexfio is an off-the-shelf — meaning it’s ready to use — dual-target antibody that works to bring together cancer-fighting immune T-cells and myeloma cells. It works by simultaneously binding to the CD3 protein at the surface of T-cells and the B-cell maturation antigen (BCMA) protein at the surface of myeloma cells.
U.S. authorities cleared Elrexfio as a fixed-dose, under-the-skin (subcutaneous) injection given once weekly. It has the possibility for injections to be reduced to every other week if clinical responses are favorable after about six months.
With the approval of Elrexfio, patients have a new off-the-shelf treatment option that can be delivered on an ongoing basis in community clinics, where the majority of patients with multiple myeloma receive their care.
Pfizer noted that it’s the first therapy of its kind with the option of dosing every other week, which may make treatment more convenient for patients and reduce its side effect profile. A similar therapy, Tecvayli, by Janssen, was approved by the FDA last year, but is given weekly.
“With the approval of Elrexfio, patients have a new off-the-shelf treatment option that can be delivered on an ongoing basis in community clinics, where the majority of patients with multiple myeloma receive their care,” Jenny Ahlstrom, founder and CEO of HealthTree Foundation for Multiple Myeloma, which offers several integrated software platforms to help blood cancer patients navigate their disease.
The therapy’s conditional approval was based on data from the ongoing Phase 2 MagnetisMM-3 clinical trial (NCT04649359), which were published in part earlier this month in the journal Nature Medicine.
The published findings concerned a group of 123 multiple myeloma patients with a median age of 68 and hard-to-treat cancer. All had failed to respond to at least three prior lines of therapy — with a median of five — that did not include a BCMA-targeted treatment.
After two loading doses in the first week, all participants received an injection of 76 mg Elrexfio once a week in four-week cycles. Patients who achieved a partial response or better after receiving six or more cycles could move to every-other-week dosing.
Over a median follow-up of nearly 15 months (more than a year), 61% of patients responded to treatment, with 35% achieving a complete response or better. Median time to a response was 1.2 months, and responses deepened over time, according to the researchers.
Median response durations and survival had not been reached, meaning that not enough patients had reached those outcomes to be able to calculate the values, the team noted.
Most (80%) of those who switched to every-other-week dosing improved or maintained their response for at least six months.
Among the 97 patients who had received four or more lines of therapy, 58% responded to Elrexfio, and 82% of them were estimated to maintain response for at least nine months.
Full approval of Elrexfio dependent on confirmatory trial
The trial also enrolled 64 patients who were previously given BCMA-directed therapies. Data from this group will be published separately, but according to the company, 33% of the 63 patients who had received at least four lines of therapy responded to Elrexfio after a median follow-up of 10.2 months. A total of 84% also were estimated to sustain a response for at least nine months.
“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,” said Ajay Nooka, MD, a trial investigator and director of the Multiple Myeloma Program at the Winship Cancer Institute of Emory University, in Atlanta.
While Elrexfio’s safety profile was generally manageable, its label does come with a boxed warning about the risk of certain serious immune responses, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome.
The therapy therefore is available only through a restricted access program. Patients should be hospitalized for two days after each of the therapy’s first two loading doses to monitor for adverse reactions.
Elrexfio’s full approval is dependent on positive data from the confirmatory Phase 3 MagnetisMM-5 trial (NCT05020236). That trial, slated to run through August 2026, is expected to involve up to 854 adults with multiple myeloma who have been previously treated with Revlimid (lenalidomide) and a proteasome inhibitor.
The study is designed to test Elrexfio, alone and/or in combination with the lab-made antibody Darzalex (daratumumab), against the standard treatment combination of Darzalex, Pomalyst (pomalidomide), and dexamethasone.
This and other trials in the MagnetisMM clinical program are exploring the potential of Elrexfio, either alone or as part of a combination therapy, at various stages of disease progression. The goal, according to Pfizer, is to ultimately expand its use as an earlier line of treatment.
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