The FDA has approved Arvinas’ Veppanu (vepdegestrant) for adults with metastatic estrogen receptor–positive, HER2-negative breast cancer with ESR1 mutations whose disease has progressed after at least one endocrine therapy. The decision covers a defined subgroup after the VERITAC-2 trial data showed a progression-free survival benefit versus fulvestrant. The drug is the first FDA-approved PROTAC (proteolysis-targeting chimera), expanding the mechanism class beyond conventional target inhibitors. The approval also positions Veppanu alongside other hormone-degrading oral options that already compete in parts of the same treatment landscape. Arvinas co-developed Veppanu with Pfizer, and the label narrowing to ESR1-mutant patients reflects where the strongest efficacy signal emerged. The approval also leaves a key commercial question: whether Veppanu’s profile will translate into durable differentiation versus competing endocrine-era therapies.