Johnson & Johnson's Rybrevant (amivantamab) approval by the FDA highlights the increasing importance of bispecific antibodies in cancer treatment. These drugs, which bind to two different proteins simultaneously, offer a novel approach to target cancer cells and activate the immune system.
Bispecific Antibody Mechanism
Unlike traditional antibody drugs that block single proteins, bispecific antibodies are designed to bind to two proteins at once. In oncology, this often involves targeting a protein on the tumor cell and a protein on an immune cell, effectively bringing the two together to destroy the cancer. For example, Amgen's Blincyto, the first bispecific antibody approved in the U.S., binds to CD19 on leukemia cells and CD3 on T cells.
Rybrevant targets EGFR and cMET, two proteins involved in tumor growth and spread, and is approved for non-small cell lung cancer (NSCLC) patients with specific EGFR exon 20 insertion mutations. This mutation is present in approximately 2% of NSCLC patients.
Clinical Development Landscape
A review of bispecific antibody development reveals a focus on hematological malignancies. Many bispecific antibodies in development target CD3 on T cells, combined with a tumor-specific antigen. Common targets include CD20 in lymphoma and BCMA in multiple myeloma.
Roche is advancing mosunetuzumab and glofitamab, both targeting CD20 and CD3, in Phase 3 trials for lymphoma. AbbVie and Genmab are also developing epcoritamab, a CD20xCD3 bispecific antibody, for lymphoma. In multiple myeloma, Johnson & Johnson, Pfizer, and Regeneron are developing BCMA-targeting bispecific antibodies, with J&J also developing talquetamab, which targets GPRC5D on multiple myeloma cells and CD3.
Bispecifics in Solid Tumors
While hematological malignancies are the primary focus, bispecific antibodies are also being explored in solid tumors. Macrogenics is developing tebotelimab, which targets PD-1 and LAG3, two checkpoint proteins that regulate the immune response to cancer. Amgen is developing AMG 757, which targets DLL3, a protein associated with small cell lung cancer, and CD3.
Competition and Future Directions
The bispecific antibody field is becoming increasingly competitive, with numerous companies developing candidates for various cancer types. The success of Rybrevant and the progress of other bispecific antibodies in clinical trials suggest that this therapeutic approach holds significant promise for improving cancer treatment outcomes.
