Vepdegestrant, the first-in-class PROTAC degrader, approved for ESR1-mutated advanced breast cancer

On 1 May 2026 the FDA approved vepdegestrant (Veppanu), the first PROTAC protein degrader to reach clinical use, exclusively for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer that has progressed after at least one line of endocrine therapy. In the registrational VERITAC-2 trial (n=624, of whom 270 had ESR1-mutated tumours), median progression-free survival in the ESR1-mutated population was 5.0 months with vepdegestrant versus 2.1 months with fulvestrant (HR 0.57; 95% CI 0.42-0.77; p=0.0001), with objective responses in 19% versus 4%. The mechanism is degradation of the estrogen receptor rather than its inhibition. The approval does not extend to ER-positive disease without an ESR1 mutation.