The FDA approved Arvinas and Pfizer’s Veppanu (vepdegestrant) for ESR1-mutated, metastatic estrogen receptor-positive, HER2-negative breast cancer that has progressed after at least one endocrine therapy. The decision was based on results from the VERITAC-2 trial, where Veppanu improved progression-free survival by nearly three months versus fulvestrant for the targeted subgroup. Regulators paired the approval with a companion diagnostic path, with Guardant Health’s tissue and liquid biopsy capabilities supporting ESR1 mutation selection for patients. The approval narrows use to ESR1-mutated patients, reflecting how efficacy for this modality has concentrated in biomarker-defined populations. While the FDA greenlight adds a new class option via PROTAC-enabled estrogen receptor degradation, the program’s broader positioning has faced scrutiny from investors given the ultimate data pattern versus earlier, broader development ambitions.