Vepdegestrant (Veppanu) is now the first FDA-approved PROTAC therapy, according to the provided report, marking a regulatory milestone for targeted protein degradation in oncology. Developed as a CRBN-recruiting PROTAC, vepdegestrant degrades WT and ESR1-mutant estrogen receptor alpha, targeting ER-driven disease biology. The report states vepdegestrant delivered the first positive Phase 3 PROTAC readout, extending progression-free survival over fulvestrant in ESR1-mutant ER+/HER2− advanced breast cancer. The disclosed characterization also points to vepdegestrant’s clinical differentiation as a next-generation degradation approach. The approval further accelerates attention on PROTACs beyond early-stage concept validation, putting renewed emphasis on durability of benefit and tolerability as these therapies move into larger patient populations.