The FDA approved Arvinas and Pfizer’s PROTAC vepdegestrant (Veppanu) for a defined group of adults with metastatic estrogen receptor-positive, HER2-negative breast cancer whose disease has progressed after at least one endocrine therapy. The approval is tied to ESR1 mutations, with Guardant Health’s companion diagnostic (CDx) supporting patient selection. Across FDA communications and trial context, the decision drew on the VERITAC-2 study, where Veppanu improved progression-free survival by nearly three months versus fulvestrant. The agency’s action makes a first-in-class targeted protein-degradation option commercially available for ESR1-mutated patients. The approvals also highlight how protein-degrader development is tightening around biomarker-driven enrollment, with the CDx requirement shaping real-world uptake and access.