Vepdegestrant: First Approval.

Vepdegestrant (VEPPANU; formerly ARV 471) is a novel PROteolysis TArgeting Chimera (PROTAC) that is able to simultaneously bind the estrogen receptor (ER) and an E3 ubiquitin ligase complex, resulting in polyubiquitination of the ER and its subsequent degradation via a proteasome. It is being developed by Arvinas and Pfizer primarily as a treatment for ER+, HER2- breast cancer. In May 2026, vepdegestrant received its first global approval in the USA for adults with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy. This article summarizes the milestones in the development of vepdegestrant leading to its first approval in this indication.