Vepdegestrant (Veppanu®) has been described as the first FDA-approved PROTAC therapy, following a May 2026 approval. The oral, CRBN-recruiting PROTAC works by catalytically degrading WT and ESR1-mutant ERα. The account highlights positive phase 3 data in ESR1-mutant ER+/HER2− advanced breast cancer, reporting improved progression-free survival versus fulvestrant. The mechanism and results underline growing clinical validation for targeted protein degradation beyond established endocrine therapy pathways. If confirmed by broader outcomes over time, the regulatory debut of a PROTAC reinforces protein degradation as a practical drug modality for oncology drug development.