FDA Grants Accelerated Approval to Elranatamab-bcmm for Relapsed or Refractory Multiple Myeloma

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Elranatamab-bcmm (Elrexfio; Pfizer) is a BCMA-CD3-targeted bispecific antibody approved for adults with relapsed or refractory multiple myeloma who were previously administered at least 4 lines of therapy that included a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

The FDA has granted accelerated approval to elranatamab-bcmm (Elrexfio; Pfizer) for the treatment of adults with relapsed or refractory multiple myeloma (RRMM) who were previously administered at least 4 lines of therapy that included a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.1

Elranatamab-bcmm is a B-cell maturation antigen (BCMA)-CD3-targeted bispecific antibody (BsAb). The FDA previously granted elranatamab with Breakthrough Therapy Designation and Priority Review for this indication.

“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,” Angela Hwang, chief commercial officer and president of Global Biopharmaceuticals Business, Pfizer, said in a press release.1

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.2

The FDA based the approval on response rates and duration of response results from the single-arm, phase 2 MagnetisMM-3 trial (NCT04649359), with continued approval contingent upon verification of clinical benefit in confirmatory trials. Cohort A (BCMA-naïve = 123) of MagnetisMM-3 was evaluated to demonstrate 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.

Among patients in the study who received 4 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 9 months and a median time to first response of 1.2 months.1

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.2

Longer-term efficacy data for cohort A (n=123) showed the objective response rate was 61%, and that median duration of response, overall survival, and progression-free survival had not yet been reached at 14.7 months median follow-up.1 For patients who responded to treatment, the probability of maintaining a response at 15 months was 72%. Among those who switched to every-other-week dosing at least 6 months prior to the data cut-off date (n=50), 80% maintained or improved their response following the switch, and 38% achieved a complete response or better after the switch.

Data from cohort B (n=64) of MagnetisMM-3 found that among 63 patients who received at least 4 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 9 months.

The study also showed 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).2

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 4.2

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.

The most common adverse events to elranatamab (incidence ≥20%) were 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%) reported during clinical trials were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets.1

“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, in a press release.1 “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.”

References

1. Pfizer’s ELREXFIO™ Receives U.S. FDA Accelerated Approval for Relapsed or Refractory Multiple Myeloma. Pfizer. News release. August 14, 2023. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-elrexfiotm-receives-us-fda-accelerated-approval

2. 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.

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