Two new bispecific antibody treatments for relapsed or refractory multiple myeloma (RRMM) will soon be available to use for patients. Janssen’s Tecvayli (teclistamab-cqyv) has been granted accelerated approval by the Food and Drug Administration (FDA), while Pfizer’s elranatamab has been designated as a breakthrough therapy that will put the drug on a fast track for approval.
Bispecific antibodies work by attaching to T cells to enable them to attack cancer cells. They can work as more readily available alternatives to CAR-T treatments, or can act as a bridge to them.
Teclistamab-cqyv for Multiple Myeloma
Janssen’s Tecvayli, also known as teclistamab-cqyv, is a bispecific antibody given subcutaneously that was granted accelerated approval on October 25, 2022. The drug has been approved for use in RRMM patients who have previously received 4 or more prior lines of therapy that included a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.
The Phase 2 MajesTEC-1 trial studied the effects of teclistamab in multiple myeloma patients who had previously received a median of 5 prior lines of therapy. A total of 157 patients were enrolled and received at least 1 dose of teclistamab, with 40 patients receiving a second phase 2 dose. The patients who received a phase 2 dose achieved a 65% overall response rate, and 58% of patients received a “very good” partial response or better.
The promising results of the MajesTEC-1 trial aided in teclistamab-cqyv’s accelerated approval by the FDA.
Elranatamab for Multiple Myeloma
Pfizer’s bispecific antibody elranatamab received its breakthrough status on November 3, 2022, which will speed up the drug’s approval process and may not require the drug to be tested in large clinical trials. Similar to teclistamab-cqyv, elranatamab is also given subcutaneously.
A press release from Pfizer stated that elranatamab works by binding to B-cell maturation antigens (BCMA), “which [are] highly expressed on the surface of multiple myeloma cells, and the CD3 receptor found on the surface of T-cells, bridging them together and activating the T-cells to kill the myeloma cells. The binding affinity of elranatamab for BCMA and CD3 has been engineered to elicit potent T-cell mediated anti-myeloma activity.”
Positive results from the Phase 2 MagnetisMM-3 study led to the drug’s breakthrough designation. In the study, 94 patients were given 76 mg of elranatamab weekly with a 2-step-up priming dose regimen administered during the first week. At a median follow-up of 6.8 months, the drug was found to have a 61% overall response rate, and a 90.4% probability of maintaining a response for longer than 6 months. The dosage of 76 mg is also suggested to have a manageable safety profile in patients with triple-class refractory multiple myeloma.
Along with its breakthrough therapy designation, elranatamab has also been granted orphan drug designation by the FDA and the European Medicines Agency to treat multiple myeloma.