FDA Grants Accelerated Approval for Pfizer’s Elrexfio for Relapsed or Refractory Multiple Myeloma

Rare Daily Staff

The U.S. Food and Drug Administration has granted accelerated approval to Elrexfio for the treatment of adult patients with relapsed or refractory multiple myeloma.

The approval is for people who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. It was based on the results of the single-arm phase 2 MagnetisMM-3 trial, and continued approval for the indication is contingent upon verification of clinical benefit in a confirmatory trial(s).

Multiple myeloma (MM) 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. MM is the second most common type of blood cancer, with over 35,000 new cases of MM diagnosed annually in the U.S. and 176,000 globally. About half of those diagnosed with MM 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 shows that people with relapsed or refractory multiple myeloma (RRMM) 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 RRMM is to achieve disease control with acceptable toxicity and improved quality of life.

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.

“With significant responses in a patient population with highly refractory disease, we believe Elrexfio is poised to potentially become the new standard of care for multiple myeloma, as we plan to build upon this indication with continued development across the expansive MagnetisMM program,” said Angela Hwang, chief commercial officer and president of Global Biopharmaceuticals Business of Pfizer.

The approval of Elrexfio is based on data from response rates and duration of response. Data from cohort A of the phase 2 MagnetisMM-3 study 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, the overall response rate was 58 percent, with an estimated 82 percent maintaining the response for at least nine months. The median time to first response was 1.2 months.

The study also established Elrexfio as the first BCMA-directed therapy in the United States 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. 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 percent after a median follow-up of 10.2 months, with an estimated 84 percent maintaining the response for at least nine months.

In longer-term efficacy data for cohort A presented at the 2023 European Hematology Association meeting, the objective response rate was 61 percent, 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 percent. Among responding patients who switched to every-other-week dosing at least six months prior to the data cut-off date, 80 percent maintained or improved their response after the switch, with 38 percent 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, 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 and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome, in addition to warnings and precautions for infections, neutropenia, hepatotoxicity and embryo-fetal toxicity. The most common adverse reactions to Elrexfio (incidence ≥20 percent) are CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and fever. Elrexfio is available only through a restricted program called the Elrexfio Risk Evaluation and Mitigation Strategy. 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.

Elrexfio received Breakthrough Therapy and Orphan Drug designations and was approved under the FDA’s Accelerated Approval Program, which is designed to shorten the time of FDA review for drugs that treat serious conditions and fill an unmet medical need. The FDA review was also conducted under Project Orbis, a framework for the concurrent submission and review of oncology drugs among international partners to potentially expedite approvals. Currently, five countries (Switzerland, Brazil, Canada, Australia, and Singapore) are participating. A new drug application for Elrexfio is being evaluated by the Japanese Ministry of Health, Labour and Welfare. Additionally, a marketing authorization application for Elrexfio is currently being evaluated under the PRIME scheme by the European Medicines Agency.

Photo: Angela Hwang, chief commercial officer and president of Global Biopharmaceuticals Business of Pfizer