The FDA cleared Arvinas’ PROTAC therapy Veppanu (formerly vepdegestrant) for a defined subgroup of adults with metastatic estrogen receptor-positive, HER2-negative breast cancer harboring ESR1 mutations, following progression after at least one endocrine therapy. The approval was tied to data from the VERITAC-2 trial, where Veppanu improved progression-free survival by nearly three months versus fulvestrant. Arvinas said the decision targets a population with limited second-line options, reflecting the drug’s mechanism of targeted protein degradation of estrogen receptors rather than receptor blockade. The FDA’s label is restricted to patients with ESR1 mutations, shaping the drug’s likely uptake and commercial scope. The therapy was co-developed with Pfizer under a longstanding partnership, and the clinical program initially aimed for broader lines of therapy. As the data consolidated around ESR1 mutation status, investor expectations for broader differentiation softened. Veppanu is now positioned against an evolving oral SERD and hormone-degrading landscape in breast cancer, with companies including Eli Lilly and others already in market or advancing comparable approaches.