FDA
FDA OK's first-in-class, oral Veppanu for advanced breast cancer
On May 1, 2026, FDA approved Veppanu (vepdegestrant) for adults with ER‑positive, HER2‑negative, ESR1‑mutated advanced or metastatic breast cancer whose disease has progressed following at least one line of endocrine therapy. Veppanu is the first FDA‑approved PROTAC (PROteolysis TArgeting Chimera), a novel class of heterobifunctional protein degraders designed to directly eliminate estrogen receptor signaling rather than inhibit it. A companion diagnostic (Guardant360 CDx) was also approved to identify eligible patients via blood‑based testing.
Endocrine therapy is a mainstay for metastatic ER+/HER2‑negative breast cancer, but ESR1 mutations develop in about 40–50% of patients treated with endocrine therapy and a CDK4/6 inhibitor, leading to resistance and poorer outcomes. These patients often progress quickly and have limited treatment options after first‑line therapy. Veppanu helps address this unmet need by providing a new option that targets a key driver of endocrine resistance in ESR1‑mutated disease.
Drug approval was based on the phase 3 VERITAC‑2 trial, which enrolled patients previously treated with one to two lines of endocrine therapy, including a CDK4/6 inhibitor. The primary endpoint was progression‑free survival (PFS) assessed by blinded independent central review, with secondary endpoints including overall survival (OS) and objective response rate (ORR). Among patients with ESR1‑mutated tumors, vepdegestrant significantly improved PFS versus fulvestrant, with a median of 5.0 months compared with 2.1 months (hazard ratio 0.57; P=0.0001). The ORR was 19% with vepdegestrant and 4% with fulvestrant. OS data were immature at the time of analysis, with 16% of deaths reported.
The recommended dose of Veppanu is 200 mg orally once daily with food. The most common adverse reactions (≥10%) reported in trials were decreased white blood cells, increased AST, musculoskeletal pain, fatigue, decreased hemoglobin, decreased neutrophils, increased ALT, increased alkaline phosphatase, nausea, decreased blood potassium, increased bilirubin, decreased appetite, QT prolongation, decreased platelets, and constipation. The prescribing information includes warnings for QT prolongation and embryo-fetal toxicity.
“For patients living with ESR1 mutant, ER+/HER2 advanced breast cancer, there have been minimal second-line treatment options once standard therapies are no longer effective,” said Erika Hamilton, MD, Chief Development Officer, Late Phase, and Director, Breast Cancer Research, Sarah Cannon Research Institute, as principal investigator of the VERITAC-2 trial. “The introduction of a new, targeted treatment is an encouraging development for this community and highlights meaningful innovation in the way this disease is treated. The approval of vepdegestrant gives clinicians another tool in the breast cancer treatment arsenal and brings renewed hope to individuals who need additional options.”
Sources:
Arvinas, Inc. (2026, May 1). Press release. Arvinas Announces FDA Approval of VEPPANU (vepdegestrant) for the Treatment of ESR1m, ER+/HER2- Advanced Breast Cancer
U.S. Food and Drug Administration. (2026, May 1). News release. FDA approves vepdegestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer