Of 97 patients in the main efficacy group of a phase 2 trial, 57.7% saw their myeloma respond to a single drug. That result, from a study called MagnetisMM-3, is what carried elranatamab-bcmm, sold as Elrexfio, to accelerated approval from the FDA on August 14, 2023.
The label is narrow. It covers adults whose myeloma came back or stopped responding after four or more earlier lines of treatment, among them a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody. These are people who have run through most of the standard options.
How the drug works
Pfizer describes Elrexfio as a bispecific antibody given by subcutaneous injection. One end binds BCMA, a protein on myeloma cells. The other binds CD3 on T-cells. Bringing the two together activates the T-cells to kill the cancer cells.
What the trial showed
MagnetisMM-3 was an open-label, single-arm study with no comparison group. Its pivotal cohort A held 123 patients who had never received a BCMA-directed treatment; 97 of them with four or more prior lines formed the efficacy population. OncLive reported that the complete response rate in that group was 25.8%, and that an estimated 82% of responders would keep responding for 9 months or longer. The typical wait for a first response was 1.22 months. The median duration of response had not been reached.
A second group, cohort B, had 64 patients who had previously been treated with BCMA-targeted antibody-drug conjugates or CAR T-cell therapies. Their overall response rate was 33.3%. Longer follow-up of cohort A, presented at the 2023 EHA Congress, pointed to a 61% response rate.
Treatment began with a ramp: 12 mg on the first day, 32 mg on day 4, then 76 mg on day 8 and every week afterward. Patients who reached a partial response or better and held it for at least 2 months moved to every-other-week dosing after 24 weeks. According to OncLive, 80% of those who switched kept their response or improved it.
Side effects and the catch
CancerNetwork listed the most common adverse effects: cytokine release syndrome, fatigue, injection site reaction, diarrhea, upper respiratory tract infection and musculoskeletal pain. The more serious grade 3 and 4 events included drops in lymphocytes, neutrophils, hemoglobin, white blood cells and platelets.
Because the approval is accelerated, it depends on proof of clinical benefit in a confirmatory phase 3 trial, MagnetisMM-5, which began in 2022. The FDA had granted priority review in February 2023.
“Discovered at Pfizer, we advanced this therapy from a first-in-patient trial to approval in less than five years, because we know that time is life for people living with multiple myeloma,” said Angela Hwang, Pfizer’s chief commercial officer and president of its Global Biopharmaceuticals Business.
Sources
- FDA Approves Elranatamab for Relapsed or Refractory Multiple Myeloma | OncLive
- Elranatamab Receives Accelerated Approval in R/R Multiple Myeloma | CancerNetwork
- FDA Accelerated Approval for ELREXFIO™ (elranatamab-bcmm) | the IMF
- FDA Approves Elranatamab for Relapsed or Refractory Multiple Myeloma | OncLive
