FDA Grants Priority Review to Elranatamab in Relapsed/Refractory Myeloma

The FDA has granted a priority review to the biologics license application for elranatamab for the treatment of patients with relapsed/refractory multiple myeloma.

The FDA has granted a priority review to the biologics license application for elranatamab (PF-06863135) for the treatment of patients with relapsed/refractory multiple myeloma.1

Additionally, the European Medicines Agency (EMA) has accepted a marketing authorization application (MAA) for elranatamab for the treatment of relapsed/refractory multiple myeloma.

The BLA and MAA are supported by findings from cohort A of the phase 2 MagnetisMM-3 trial (NCT04649359), which showed that at a median follow-up of 10.4 months, the BCMA/CD3-targeted bispecific antibody elicited an objective response rate (ORR) of 61.0% (95% CI, 51.8%-69.6%), including a very good partial response or better rate of a 55.3% and a complete remission rate of 27.6%.2

“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.”

In November 2022, the FDA granted elranatamab a breakthrough therapy designationfor this population.3

MagnetisMM-3 enrolled patients with multiple myeloma that was refractory to at least 1 proteasome inhibitor, 1 immunomodulatory drug, and 1 anti-CD38 antibody. Patients in cohort A could not have received prior BCMA-directed therapy, and cohort B included patients who received prior treatment with a BCMA-directed antibody-drug conjugate or CAR T-cell therapy.4

Patients in cohort A were administered step-up dosing with elranatamab at 12 mg on day 1 and 32 mg on day 4. The bispecific antibody was then given subcutaneously at 76 mg once per week. Notably, step-up dosing was started later in the study, and 119 of 123 enrolled patients received it. For patients who received 6 or more cycles and achieved a partial response or better for at least 2 months, the dosing interval was once every 2 weeks.1

ORR served as the trial’s primary end point. Secondary end points included ORR by baseline extramedullary disease status, duration of response (DOR), complete response rate, duration of complete response, progression-free survival, minimal residual disease (MRD) negativity rate, overall survival, and safety.4

Additional data from cohort A presented at the 2022 ASH Annual Meeting showed that the median duration of treatment was 5.6 months.2 The median duration of response was not yet reached at the October 14, 2022, data cutoff, and 77.3% of responses were ongoing (n = 58/75). The 9-month DOR rate was 84.4%, and the 9-month PFS rate was 63.0%.

Regarding safety, step-up dosing helped mitigate the rate and severity of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). In the 119 patients who received step-up dosing, all CRS and ICANS events were grade 1/2, and the rates of CRS and ICANS were 56.3% and 3.4%, respectively. Additionally, 90.6% of CRS events occurred during step-up dosing, and 98.8% were reported during the first 3 doses of elranatamab.

Elranatamab is also under further investigation alone and in combination with daratumumab (Darzalex) for patients with relapsed/refractory multiple myeloma in the phase 3 MagnetisMM-5 study (NCT05020236). Additionally, the phase 3 MagnetisMM-7 study (NCT05317416) is evaluating elranatamab as maintenance therapy, compared with lenalidomide (Revlimid), for patients with newly diagnosed multiple myeloma.

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
  3. Pfizer’s elranatamab granted FDA breakthrough therapy designation for relapsed or refractory multiple myeloma. News release. Pfizer. November 3, 2022. Accessed February 22, 2023. https://www.pfizer.com/news/press-release/
  4. MagnetisMM-3: study of elranatamab (PF-06863135) monotherapy in participants with multiple myeloma who are refractory to at least one PI, one IMiD and one anti-CD38 mAb. ClinicalTrials.gov. Updated October 5, 2022. Accessed February 22, 2023. https://clinicaltrials.gov/ct2/show/NCT04649359