FDA Approval

FDA Approves Vepdegestrant (Veppanu) for ESR1-Mutated, ER-Positive, HER2-Negative Advanced Breast Cancer

Edited by:
Anthony Calabro, MA

Key Highlights

  • Vepdegestrant was approved for adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer following disease progression on endocrine therapy.
  • The phase 3 VERITAC-2 trial demonstrated that vepdegestrant significantly improved progression-free survival compared with fulvestrant in patients with ESR1-mutated tumors.
  • The FDA approved the Guardant360 CDx as a companion diagnostic to identify patients with ESR1 mutations eligible for treatment.
  • The recommended dose of vepdegestrant is 200 mg taken orally once daily with food until disease progression worsens or unacceptable toxicity develops.

On May 1, the FDA approved vepdegestrant (Veppanu), a heterobifunctional protein degrader, for adults with estrogen receptor–positive, human epidermal growth factor receptor 2–negative, ESR1-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test. Vepdegestrant is indicated for patients with disease progression following at least 1 line of endocrine therapy. The FDA also approved the Guardant360 CDx as a companion diagnostic to identify patients with ESR1 mutations eligible for treatment.

The approval was based on results from the phase 3 VERITAC-2 trial (NCT05654623), a randomized, open-label, active-controlled, multicenter study of 624 patients, including 270 with ESR1-mutated tumors. Patients were randomized to receive vepdegestrant orally once daily or fulvestrant administered intramuscularly. In the ESR1-mutated population, vepdegestrant demonstrated a statistically significant improvement in progression-free survival compared with fulvestrant (median, 5.0 vs 2.1 months; hazard ratio, 0.57; 95% CI, 0.42-0.77; P = .0001). Objective response rates were 19% and 4%, respectively. Overall survival data were immature at the time of analysis.

The recommended dose of vepdegestrant is 200 mg taken orally once daily with food until disease progression worsens or unacceptable toxicity develops. The FDA noted that this application was approved 1 month ahead of the agency’s goal date using the Assessment Aid, a voluntary submission to facilitate review.

Reference
U.S. Food and Drug Administration. FDA approves vepdegestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. May 1, 2026. Accessed May 1, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-vepdegestrant-er-positive-her2-negative-esr1-mutated-advanced-or-metastatic-breast