Janssen, a subsidiary of Johnson & Johnson, recently announced that teclistamab, the world's first BCMA/CD3 bisspecificity antibody, has been approved by the FDA for the treatment of relapsed or refractory multiple myeloma.
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Teclistamab, sold under the trade name TECVAYLI®, is a fully humanized bisecific antibody targeting CD3 receptors on both BCMA and T cells. It can recruit CD3-positive T cells to the vicinity of BCMA-expressing myeloma cells and stimulate T cells to kill tumor cells.
Teclistamab was first granted PRIME(Priority drug) designation by the European Medicines Agency (EMA). On June 1, teclistamab was granted Breakthrough Therapy Designation (BDT) by the FDA. Two months later, Teclistamab injection was included in the Breakthrough therapy category by NMPA. It is used for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least three previous lines of therapy. It is also included in the breakthrough treatment variety in China and the United States, indicating that it has a significant effect in the treatment of multiple myeloma.
The approval of Teclistamab was based on the positive results of the MajesTEC-1 study, an open-label, multicenter, phase I/II trial (Registration No. NCT03145181, NCT04557098) to evaluate the efficacy and safety of Teclistamab in patients with relapsed or refractory multiple myeloma.
The trial, published in the top journal NEJM, involved 165 patients who received weekly subcutaneous injections of Teclistamab at a dose of 1.5 mg/kg, followed by increments of 0.06 mg/kg and 0.3 mg/kg.
The results showed that the overall response rate (ORR) was 63% (104/165), 58.8% of the patients had a good partial response (VGPR) or above, and 39.4% of the patients had a complete response (CR) or above.
The median duration of response was 18.4 months, median progression-free survival was 11.3 months, and median overall survival was 18.3 months. The most common adverse event with respect to safety was cytokine release syndrome (CRS) (72%; 0.6% grade 3, no grade 4), neutropenia (71%; 64% grade 3 or 4) and anemia (55%; 37% level 3 or 4).
BCMA is a member of tumor necrosis factor superfamily protein, which is mainly expressed in malignant and normal plasma cells and some mature B cells, but not in important tissues. Bcma is an effective target for the treatment of multiple myeloma.
BCMA dual antidrugs have both good efficacy and safety. Bcma-targeted CAR-T drugs are effective in the treatment of blood cancer, with ORR of more than 90% for many drugs, but including severe immune effector cell-associated neurotoxic syndrome and CRS toxicity problems. Although the toxicity of ADC drugs is low, there is a certain gap between the therapeutic effect of BCMA and CAR-T and dual-antibody drugs. The efficacy and safety of BCMA dual-antibody drugs are between those of CAR-T and ADC.
As early as the 1980s, CD3 targets have entered the field of dual-antibody development. In 1985, the concept of T-cell reorientation was first proposed. After 30 years of research, CD3 targets have gradually matured.
CD3 molecule is widely distributed on the surface of mature T cells, and it is combined with T cell antigen recognition receptor (TCR) to form a complex receptor molecule to activate T cells and realize T cell reorientation.
Among the dual-antibody drugs already on the market, Amgen's Blinatumomab, Genentech's Mosunetuzumab, and the newly launched teclistamab all target CD3. As well as glofitamab and epcotitama, both of which made rapid progress, have targeted CD3, which has become a major target for dual antibody drug development worldwide.
According to the data, a total of 229 dual antibodies already on the market and under research worldwide contain CD3 targets, which is much higher than the second one, PDL-1. The BCMA×CD3 target combination pipeline ranks the second with 17, only second to CD3×CD20 targets. There are 10 domestic dual antibodies combined with CD3×BCMA, most of which are in the early clinical stage.
In addition, J&J has a first-in-class CD3 dual antibody, Talquetamab(GPRC5D x CD3), which has shown excellent efficacy in multiple myeloma.
So far this year, four dual-antibody drugs have been approved, while Roche's glofitamab and AbbVie's epcoritama have filed for approval and are expected to be approved soon.
