Elranatamab Application Granted Priority Review For Relapsed/Refractory Multiple Myeloma

The FDA has granted priority review to the biologics license application for elranatamab for the treatment of patients with relapsed or refractory multiple myeloma (RRMM).¹ The FDA is expected to decide in 2023. Additionally, the European Medicine’s Agency (EMA) accepted a marketing authorization application for the agent.¹

The applications leverage data from cohort A (n = 123) of the MagnetisMM-3 trial (NCT04649359). This ongoing, open-label, multicenter, single-arm, phase 3 study was designed to assess the safety and efficacy of elranatamab monotherapy in patients with RRMM. Patients who were enrolled to this trial were heavily pretreated, with previous experience with at least 3 classes of therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.¹

The objective response rate was 61% at a median follow-up of 10.4 months. This included 55% of patients who had a very good partial response or better. The percentage of responders expected to maintain their response at 9 months was 84%.^1,2

Moreover, current data indicate that the safety profile is tolerable, according to Pfizer, the manufacturer. The agent is administered with a 2-step-up priming dose regimen (12 mg/32 mg) in an attempt to mitigate the rate and severity of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). Among patients who experienced CRS, all cases were grade 1 or 2 and most occurred after the first or second dose (43% and 24% of cases, respectively). After the third dose, 6% of patients experienced CRS and fewer than 1% of patients reporting the effect after dose 4. ICANS was not common or severe and no fatal neurotoxicities were observed.^1,2

Elranatamab is an investigational, off-the-shelf, humanized BCMA CD3-targeted bispecific antibody. It is designed so that 1 arm binds directly to the specific antigens on the cancer cells and the other binds to the T cells. This is thought to elicit mediated antimyeloma activity.

Of note, elranatamab is administrated subcutaneously, which may offer convenience over intravenous administration. As part of the trial, patients received subcutaneous elranatamab at a dose of 76 mg weekly on a 29-day cycle with a step-up priming dose regimen, where 12-mg and 32-mg doses are administered on days 1 and 4 of cycle 1. For those who received at least 6 cycles, and who achieved a partial response or better for at least 2 months, the dosing interval was once every 2 weeks.^1,2

Additional data, which was reported at the 2022 ASH Annual Meeting showed that the median duration of treatment was 5.6 months. Moreover, as of an October 14, 2022, data cutoff, 77.3% of responses were ongoing (n = 58 of 75). The 9-month response rate was 84.4% and the 9-month progression-free survival rate was 63.0%.²

Other avenues of research with elranatamab include the phase 3 MagnetisMM-5 study (NCT05020236) and the phase 3 MagnetisMM-7 study (NCT05317416). The first of these trials is evaluating the bispecific antibody alone and in combination with daratumumab (Darzalex) for patients with RRMM; the latter is assessing the agent in the maintenance setting compared with lenalidomide (Revlimid), for those with newly diagnosed disease. ¹

“Today, multiple myeloma is a fatal hematologic malignancy, with a median survival of just over 5 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,” Chris Boshoff, MD, PhD, chief development officer, Oncology and Rare Disease, Pfizer Global Product Development, stated in a news 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.”¹

References

1. Pfizer’s elranatamab receives FDA and EMA filing acceptance. News release. Pfizer. February 22, 2023. Accessed February 22, 2023. https://investors.pfizer.com/Investors/News/
2. Bahlis NJ, Tomasson MH, Mohty M, et al. Efficacy and safety of elranatamab in patients with relapsed/refractory multiple myeloma naïve to B-cell maturation antigen (BCMA)-directed therapies: results from cohort A of the Magnetismm-3 study. Blood. 2022;140(suppl 1):391-393. doi:10.1182/blood-2022-162440