The FDA has granted 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 Breakthrough Therapy designation to elranatamab for this indication.
“Today, multiple myeloma is a fatal hematologic malignancy with a median survival of just over five years. As a standard of care, bispecific BCMA antibodies herald a new treatment paradigm that can profoundly impact the lives of people living 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 due to its favorable clinical outcomes and convenient subcutaneous route of administration. We look forward to working with the FDA and EMA to bring this new innovative medicine to patients worldwide.”
Elranatamab was designed to bind 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. Elranatamab’s binding affinity for BCMA and CD3 was 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 phase 2, open-label, multicentre, single-arm study MagnetisMM-3 (NCT04649359). The ongoing study was designed to evaluate the safety and efficacy of elranatamab monotherapy in patients with RRMM.
Patients received elranatamab 76 mg subcutaneously weekly in a 28-day cycle with a step-up base dose. For the priming schedule, 12 mg and 32 mg were administered on days 1 and 4 of cycle 1, respectively.
In patients who received 6 or more cycles and had a partial response or better for at least 2 months, the dosing interval was once every 2 weeks. Patients enrolled in the study represented a heavily pretreated population who had previously received at least 3 classes of therapy including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.
Data presented at the 64th Annual Meeting and Exposition of the American Society of Hematology showed that patients receiving elranatamab as their first BCMA-directed 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% chance of maintaining a response at 9 months, the investigators said.
The study investigators also noted that elranatamab has a manageable safety profile. Among 119 patients in Cohort A administered the 2-step-up priming dosing 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. In addition, 6% of patients had CRS after dose 3 and less than 1% had CRS after dose 4.
No cases of common or severe ICANS (3%) were observed, with only grade 1/2 cases reported, and no fatal neurotoxicity events were observed. In addition to Breakthrough Therapy designation, elranatamab previously received FDA Orphan Drug designation for the treatment of MM. Pfizer expects the FDA’s decision on the BLA in 2023.
Pfizer’s Elranatamab Receives FDA and EMA Approval Pfizer. press release. https://investors.pfizer.com/Investors/News/news-details/2023/Pfizers-Elranatamab-Receives-FDA-and-EMA-Filing-Acceptance/default.aspx. February 22, 2023.