Johnson & Johnson’s Tecvayli (teclistamab-cqyv) has been approved by the FDA, and Pfizer’s elranatamab received breakthrough status that should speed its approval. Bispecific antibodies may be a bridge to CAR-T treatments or an alternative to them.
The FDA recently approved a bispecific antibody for relapsed or refractory multiple myeloma (RRMM) and granted breakthrough therapy designation for another one.
The FDA approved Johnson & Johnson’s Tecvayli (teclistamab-cqyv) for adult with RRMM who previously received four or more prior lines of therapy, including a proteasome inhibitor, immunomodulatory drug and anti-CD38 monoclonal antibody.
Tecvayli is a first-in-class bispecific T-cell engager antibody — the commonly used shorthand is bispecific antibody — that is administered subcutaneously.
The off-the-shelf (ready to use) therapy “uses innovative science to activate the immune system by binding to the CD3 receptor expressed on the surface of T-cells and to the B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells,” the press release said. Put more simply, bispecific antibodies are designed to attach to T cells and to cancer cells so the T cells attack the cancer cells.
How exactly bispecific antibodies will be used among the multiple lines of treatment for multiple myeloma is unclear. They may wind up being used as bridge to chimeric antigen receptor (CAR)-T cell therapy or as an alternative to CAR-T treatment that is more readily available.
The FDA granted accelerated approval based on response rate. “The approval of Tevayli, which demonstrated an overall response rate of more than 60% in heavily pretreated patients, underscores our commitment to translate science into medicines as we strive toward our goal of one day eliminating this disease,” said Peter Lebowitz, M.D., Ph.D., global therapeutic area head of oncology for Janssen, which is part of Johnson & Johnson.
The pivotal Phase 2 MajesTEC-1 clinical trial included patients who had received a median of five prior lines of therapy. They achieved an overall response rate (ORR) of 61.8%, with 28.2% of patients achieving a complete response (CR) or better (CR or stringent complete response [sCR]).
With a median follow-up of 7.4 months, the estimated duration of response (DOR) rate was 90.6% at six months and 66.5% at nine months.
Meanwhile, Pfizer’s bispecific antibody for RRMM, called elranatamb, received breakthrough status from the FDA. Breakthrough status is supposed to speed up the FDA’s drug approval process and may mean that drug developer won’t have to test the new drug in large clinical trials.
“The FDA’s breakthrough designation recognizes the potential of elranatamab as an innovative medicine for people with multiple myeloma whose disease has relapsed or is refractory to existing treatments, which at present leaves very few avenues for staving off this currently incurable cancer,” said Chris Boshoff, M.D., Ph.D., chief development officer, Oncology and Rare Disease for Pfizer Global Product Development, in a news release.
Elranatamab is administered subcutaneously, which offers more convenience over intravenous administration and may mitigate the risk of potential adverse events, such as cytokine release syndrome (CRS), Pfizer said.
“Elranatamab is designed to bind to BCMA, which is highly expressed on the surface of multiple myeloma (MM) 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,” the Pfizer press release said.
The breakthrough therapy designation is based on a Phase 2 study which showed that elranatamab demonstrated a manageable safety profile and an overall response rate (ORR) of 61% at a median follow-up of 6.8 months. Among responders, there was 90.4% probability of maintaining a response greater than 6 months.
In addition to the breakthrough therapy designation, elranatamab has been granted orphan drug designation by the FDA and the European Medicines Agency to treat multiple myeloma.