Vepdegestrant (Veppanu®; ARV-471), an oral CRBN-recruiting PROTAC, became the first FDA-approved PROTAC therapy as of May 2026, marking a regulatory milestone for targeted protein degradation in oncology. The therapy degrades wild-type and ESR1-mutant ERα and delivered a positive Phase 3 outcome versus fulvestrant in ESR1-mutant ER+/HER2− advanced breast cancer. The reported milestone underscores both clinical and technical maturation in PROTAC development—linking receptor-specific degradation to meaningful progression-free survival gains in an established treatment setting. Regulatory information centered on the program’s Phase 3 basis and positioned vepdegestrant as a new option for patients with ESR1-mutant disease. For the category, the approval functions as a reference point for future PROTACs, especially those aiming to demonstrate superiority or clinically meaningful benefit over current endocrine therapies.