FDA Grants Priority Review to Elranatamab for Relapsed/Refractory Multiple Myeloma

The FDA has awarded Priority Review to a Biologics License Application (BLA) for elranatamab (PF-06863135; Pfizer Inc.) for the treatment of relapsed or refractory multiple myeloma (RRMM). The novel drug is a B-cell maturation antigen (BCMA)-CD3-targeted bispecific antibody (BsAb). The FDA previously granted elranatamab with Breakthrough Therapy Designation for this indication.

"Today, multiple myeloma is a fatal hematologic malignancy, with a median survival of just over five years. As an off-the-shelf treatment, BCMA bispecific antibodies are heralding a new treatment paradigm that can greatly impact the lives of people with this disease.” said Chris Boshoff, MD, PhD, chief development officer, Oncology and Rare Disease, Pfizer Global Product Development, in a press release. “We believe that elranatamab, if approved, has the potential to become the next standard of care for multiple myeloma given its favorable clinical results and convenient subcutaneous route of administration. We look forward to working with the FDA and EMA to bring this new innovative medicine to patients globally.”

Elranatamab was developed to attach to BCMA, which is highly expressed on the surface of MM cells. The CD3 receptor found on the surface of T-cells connects and activates them to kill myeloma cells. The binding affinity of elranatamab for BCMA and CD3 has been engineered to elicit potent T-cell mediated anti-myeloma activity.

The BLA for elranatamab was primarily based on data from cohort A (BCMA-naïve = 123) of the open-label, multicenter, single-arm, phase 2 MagnetisMM-3 (NCT04649359) study. The ongoing study was designed to evaluate the safety and efficacy of elranatamab monotherapy in patients with RRMM.

Patients were administered subcutaneous elranatamab 76 mg weekly on a 28-day cycle with a step-up priming dose regimen. For the priming regimen, 12 mg and 32 mg were administered on days 1 and 4, respectively, during cycle 1.

For those administered 6 or more cycles and who showed a partial response or better for at least 2 months, the dosing interval was once every 2 weeks. Patients enrolled in the trial represented a heavily pretreated population previously administered at least 3 classes of therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Data presented at the 64th American Society of Hematology Annual Meeting and Exposition showed that patients administered elranatamab as their first BCMA-targeted therapy had an objective response rate of 61% over a median follow up of 10.4 months—55% had a very good partial response rate or better—and an 84% probability of maintaining the response at 9 months, according to the investigators.

The study investigators also found that elranatamab has a manageable safety profile. Among 119 patients in cohort A administered the 2-step-up priming dose regimen (12/32 mg), the researchers observed improvements in the rate and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

All cases of CRS were grade 1 or 2, with 43% of patients experiencing CRS after the first dose and 24% after the second dose. Further, 6% of patients had a CRS following dose 3 and fewer than 1% experienced CRS following dose 4.

There were no observed cases of common or severe ICANS (3%), with only grade 1/2 cases reported and there were no observed fatal neurotoxicity events. In addition to the Breakthrough Therapy Designation, elranatamab was also previously granted FDA Orphan Drug Designation for the treatment of MM. The FDA’s decision on the BLA is expected in 2023, according to Pfizer.

Reference

Pfizer’s Elranatamab Receives FDA and EMA Filing Acceptance. Pfizer. News release. https://investors.pfizer.com/Investors/News/news-details/2023/Pfizers-Elranatamab-Receives-FDA-and-EMA-Filing-Acceptance/default.aspx. February 22, 2023.