Arvinas (Nasdaq: ARVN) and Pfizer have received FDA approval for VEPPANU (vepdegestrant), a new oral treatment for adults with ER+/HER2-, ESR1-mutated advanced or metastatic breast cancer who have progressed on at least one line of endocrine therapy. The approval marks the first time the FDA has approved a PROTAC (PROteolysis TArgeting Chimera) therapy – an entirely new class of drug that harnesses the body’s natural protein disposal system to degrade disease-causing proteins.
The approval addresses a significant treatment gap. While endocrine therapy remains a cornerstone of metastatic ER+/HER2- breast cancer treatment, up to 40-50% of patients treated with endocrine therapy and a CDK4/6 inhibitor develop ESR1 mutations, leading to treatment resistance and poor prognosis. These patients often experience rapid disease progression with limited options after first-line therapy.
In the Phase 3 VERITAC-2 trial of 270 patients with ESR1 mutations, VEPPANU reduced the risk of disease progression or death by 43% compared to fulvestrant. Median progression-free survival was 5 months versus 2.1 months. VEPPANU is also taken orally, compared to fulvestrant which requires intramuscular injection.
“For patients living with ESR1 mutant, ER+/HER2- advanced breast cancer, there have been minimal second-line treatment options once standard therapies are no longer effective,” said Erika Hamilton, MD, chief development officer at Sarah Cannon Research Institute and principal investigator of the VERITAC-2 trial. “The introduction of a new, targeted treatment is an encouraging development for this community and highlights meaningful innovation in the way this disease is treated.”
Breast cancer is the most common cancer among women worldwide, and the subset of patients with ESR1 mutations who have exhausted first-line endocrine therapy represent one of the most clinically challenging populations in oncology. VEPPANU was developed jointly by Arvinas and Pfizer, with the companies now in the process of selecting a third-party commercialization partner.
Arvinas was founded based on PROTAC research at Yale University by Professor Craig Crews, PhD.
