Breaking New Ground in Oncology: FDA Acceptance of Vepdegestrant NDA Marks a Milestone for PROTAC Therapies in Breast Cancer.

On August 8, 2025, Arvinas and Pfizer announced that the FDA had accepted the NDA for vepdegestrant (ARV-471, PF-07850327) for the treatment of patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) and ESR1-mutated advanced or metastatic breast cancer who have previously received endocrine-based therapy. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of June 5, 2026. Vepdegestrant, a first-in-class oral PROTAC ® estrogen receptor (ER) degrader, is a heterobifunctional molecule. It consists of an ER-binding moiety derived from lasofoxifene, a cereblon (CRBN)-targeting ligand based on lenalidomide, and a rigid N-containing heterocycle linker. This structure enables selective recruitment of the E3 ubiquitin ligase CRBN to ER, driving ubiquitination and proteasomal degradation.