NDA Submission of Vepdegestrant (ARV-471) to U.S. FDA: The Beginning of a New Era of PROTAC Degraders

Vepdegestrant (ARV-471) is a promising PROTAC degrader targeting the estrogen receptor for treating ESR1-mutated, ER+/HER2- advanced or metastatic breast cancers. Arvinas and Pfizer have submitted a New Drug Application to the FDA based on positive results from the Phase 3 VERITAC-2 trial, potentially making it the first FDA-approved PROTAC degrader. Vepdegestrant effectively degrades ER in various breast cancer models, including those resistant to current therapies, and shows significant antitumor efficacy. It offers advantages over traditional small molecule inhibitors by overcoming drug resistance and targeting "undruggable" proteins. The development of vepdegestrant marks a significant milestone in the field of targeted protein degradation and cancer treatment.