On August 14, 2023, the U.S. Food and Drug Administration (FDA) granted accelerated approval to elranatamab-bcmm (Elrexfio™), a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, for adults with relapsed or refractory multiple myeloma (MM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

FDA Grants Accelerated Approval to Elranatamab-Bcmm for Multiple Myeloma

Efficacy was evaluated in MagnetisMM-3 (NCT04649359), an open-label, single-arm, multicenter study that included patients with relapsed or refractory MM who are refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-CD38 antibody. Patients had measurable disease according to International Myeloma Working Group (IMWG) criteria at enrollment.

The main efficacy outcome measures were objective response rate (ORR) and duration of response (DOR), as assessed by a blinded independent central review based on IMWG criteria. The primary efficacy population consisted of 97 patients naive to prior BCMA-directed therapy and who had received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The ORR in the 97 patients receiving the recommended dose was 57.7% (95% CI = 47.3%, 67.7%). After a median follow-up of 11.1 months among responders, the median DOR was not reached (95% CI = 12 months, not reached). The DOR at six months was 90.4% (95% CI = 78.4%, 95.9%) and 82.3% (95% CI = 67.1%, 90.9%) at nine months.

The prescribing information for elranatamab-bcmm has a boxed warning for life-threatening or fatal cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS). Among patients who received elranatamab-bcmm at the recommended dose, neurologic toxicity occurred in 59% of patients, CRS in 58%, and ICANS in 3.3%. Grade 3 or 4 neurologic toxicity occurred in 7% of patients, and grade 3 CRS occurred in 0.5%.

Elranatamab-bcmm is only available through a restricted program under a risk evaluation and mitigation strategy (REMS), called the Elrexfio REMS, because of the risks of CRS and neurologic toxicity, including ICANS.

The most common adverse reactions reported in at least 20% of patients treated with elranatamab-bcmm were CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, rash, cough, nausea, pyrexia, and decreased appetite. The most common grade 3–4 laboratory abnormalities reported in at least 20% of patients were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets.

The recommended elranatamab-bcmm dosages are step-up dose 1 of 12 mg on day 1, step-up dose 2 of 32 mg on day 4, first treatment dose of 76 mg on day 8, and then 76 mg weekly thereafter through week 24. For patients who have received at least 24 weeks of elranatamab-bcmm and have achieved at least partial responses and maintained responses for at least two months, the dose interval should transition to an every-other-week schedule. Patients may continue elranatamab-bcmm until they experience disease progression or unacceptable toxicity.

The review was conducted under Project Orbis, an initiative of FDA Oncology Center of Excellence (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, FDA collaborated with the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency, Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.

The review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

The application was granted priority review, breakthrough designation and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.