The U.S. Food and Drug Administration has approved a revolutionary new type of breast cancer drug that works by destroying cancer-driving proteins from within cells, marking the first time the agency has greenlit a technology called targeted protein degradation. The drug, VEPPANU (vepdegestrant), offers a new oral treatment option for adults with a common and aggressive form of advanced breast cancer that has stopped responding to standard hormone therapy.
The approval specifically covers patients with estrogen receptor-positive (ER+), HER2-negative advanced or metastatic breast cancer who carry a mutation in the ESR1 gene. Up to 40 to 50 percent of patients treated with initial endocrine therapy and a CDK4/6 inhibitor develop these mutations, which drive resistance to existing treatments and lead to rapid disease progression. In the pivotal VERITAC-2 Phase 3 trial involving 270 patients with ESR1 mutations, VEPPANU reduced the risk of disease progression or death by 43 percent compared with the current standard of care, fulvestrant. Median progression-free survival was 5 months on VEPPANU versus 2.1 months on fulvestrant.
VEPPANU belongs to a novel class of therapies called PROTACs, which stands for PROteolysis TArgeting Chimeras. Unlike traditional drugs that block a protein’s activity, PROTACs act like molecular garbage collectors, tagging the estrogen receptor for destruction by the cell’s own waste disposal system. This approach may overcome resistance that develops when cancer cells learn to evade standard hormone blockers. The drug is taken as a once-daily pill, offering a convenient alternative to fulvestrant, which requires intramuscular injections at a clinic. Most side effects were mild to moderate, with the most common including decreased white blood cells, musculoskeletal pain, fatigue, nausea, and changes in liver enzymes.
Arvinas, the company that pioneered the PROTAC technology based on research at Yale University, developed VEPPANU jointly with Pfizer. The companies are now working to select a third-party partner to bring the drug to patients as quickly as possible. For the thousands of patients living with ESR1-mutant breast cancer who have faced limited options after first-line therapy fails, this approval represents a fundamentally new way to fight the disease and a hopeful step toward more durable control of advanced breast cancer.