FDA Accepts NDA for Vepdegestrant, a First-in-Class Oral PROTAC® Estrogen Receptor Degrader, for ESR1-Mutated ER+/HER2- Advanced Breast Cancer

Arvinas and Pfizer recently announced that the U.S. FDA has accepted their New Drug Application (NDA) for vepdegestrant, intended for the treatment of patients who have previously received endocrine therapy, are estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-), and are accompanied byESR1Patients with mutant advanced or metastatic breast cancer. The PDUFA date for this application is June 5, 2026.According to the press release, vepdegestrant is the first PROTAC to demonstrate clinical benefit in breast cancer patients.®Therapy; if approved, this therapy will become the first PROTAC to be approved by the U.S. FDA.®Estrogen Receptor Degrader.

The submission of this vepdegestrant marketing application is primarily based on the positive results from the VERITAC-2 Phase 3 clinical trial. Analysis shows that, in carriersESR1In patients with mutated hormone receptor (HR)-positive, HER2-negative breast cancer, vepdegestrant demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to the active control. These patients experienced disease progression after prior treatment with CDK4/6 inhibitors and endocrine therapy.In carryingESR1In the mutated patient population, the risk of disease progression or death was reduced by 43% (HR=0.57; 95% CI: 0.42–0.77, P<0.001), with a PFS of 5.0 months in the vepdegestrant group compared to only 2.1 months in the control group.In carryingESR1Among all patient subgroups with mutations, the benefits of vepdegestrant were consistent.

Vepdegestrant is a potential “first-in-class” oral PROTAC.®Degraders, which use the body's natural protein degradation system to specifically target and degrade estrogen receptors.It has been granted Breakthrough Therapy Designation by the U.S. FDA for the treatment of pretreated ER-positive, HER2-negative breast cancer.

References:

[1] Arvinas Announces FDA Acceptance of the New Drug Application for Vepdegestrant for the Treatment of ESR1m, ER+/HER2- Advanced Breast Cancer. Retrieved August 11, 2025 from https://ir.arvinas.com/news-releases/news-release-details/arvinas-announces-fda-acceptance-new-drug-application

[2] Arvinas Announces Submission of New Drug Application to U.S. FDA for Vepdegestrant for Patients with ESR1-Mutated ER+/HER2- Advanced or Metastatic Breast Cancer. Retrieved June 6, 2025 from https://ir.arvinas.com/news-releases/news-release-details/arvinas-announces-submission-new-drug-application-us-fda