Pfizer’s ELREXFIO™ Receives U.S. FDA Accelerated Approval for Relapsed or Refractory Multiple Myeloma

Pfizer Inc. (NYSE:PFE) today announced the U.S. Food and Drug Administration (FDA) has granted accelerated approval to ELREXFIO™ (elranatamab-bcmm) for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Approval was based on the results of the single-arm Phase 2 MagnetisMM-3 trial, and continued approval for this indication is contingent upon verification of clinical benefit in a confirmatory trial(s). 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.

“ELREXFIO reflects our ongoing commitment to developing scientific breakthroughs that meaningfully improve outcomes for people with cancer. Discovered at Pfizer, 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,” said Angela Hwang, Chief Commercial Officer and President of Global Biopharmaceuticals Business, Pfizer. “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.”

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.

“Accessibility is key to unlocking the potential impact of new treatment options. Unfortunately, novel therapies for triple-class-exposed multiple myeloma can be out of reach for medically underserved populations,” said Jenny Ahlstrom, Founder and Chief Executive Officer of the HealthTree Foundation for Multiple Myeloma. “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.”

For patients who are prescribed ELREXFIO, Pfizer offers the support of Patient Access Navigators, through our Pfizer Oncology Together program, who provide personalized services for all aspects of treatment, including financial assistance resources, treatment support, and resources to navigate potential insurance and coverage issues.

ELREXFIO received Breakthrough Therapy Designation 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 (EMA).

The extensive MagnetisMM clinical development program is investigating ELREXFIO’s use across the entire spectrum of myeloma progression, from newly diagnosed multiple myeloma to RRMM. Ongoing registrational-intent trials are exploring ELREXFIO both as monotherapy and in combination with standard or novel therapies. These include the Phase 3 MagnetisMM-5 trial in the double-class exposed setting and MagnetisMM-7 with ELREXFIO as maintenance treatment in newly diagnosed patients after transplant.