Announcement • May 03
Arvinas Inc. and Pfizer Inc. Receive FDA Approval for Veppanu for Treatment Of ESR1m, ER+/HER2- Advanced Breast Cancer
Arvinas, Inc., with its partner Pfizer Inc. announced that the U.S. Food and Drug Administration (FDA) has granted approval for VEPPANU (vepdegestrant) for the treatment of adults with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), estrogen receptor 1 (ESR1)-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy. This approval marks the first time the FDA has approved a PROteolysis TArgeting Chimera (PROTAC), a type of heterobifunctional protein degrader therapy. VEPPANU offers a new therapeutic option in ER+/HER2-, ESR1-mutated advanced or metastatic breast cancer, where treatment resistance remains a major clinical challenge. Breast cancer is the most common cancer among women worldwide, with many tumors driven by estrogen receptor signaling. While endocrine therapy remains a cornerstone of metastatic ER+/HER2- breast cancer treatment, up to 40-50% of patients treated with endocrine therapy and a CDK4/6 inhibitor have ESR1 mutations, resulting in endocrine resistance and poor prognosis. These patients often experience rapid disease progression and face limited options after first-line therapy. The FDA approval of VEPPANU addresses a significant unmet need, offering a new treatment option for adults with ESR1-mutant, ER+/HER2- advanced breast cancer by targeting a key biological driver of resistance to current therapies. VEPPANU was discovered by Arvinas and jointly developed by Arvinas and Pfizer. FDA approval was granted based on data from VERITAC-2 (NCT05654623), a global, randomized, open-label, pivotal Phase 3 clinical trial evaluating vepdegestrant versus fulvestrant. In the trial, among patients with an ESR1 mutation (n=270), vepdegestrant demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), reducing the risk of disease progression or death by 43% compared to fulvestrant. Median PFS was 5 months (95% CI: 3.7, 7.4) in the vepdegestrant arm and 2.1 months (95% CI: 1.9, 3.5) in the fulvestrant arm (hazard ratio 0.57 [95% CI: 0.42, 0.77]; p-value 0.0001). Overall survival was immature with 16% of deaths in this population at the time of the PFS analysis. The majority of adverse events (AEs) with vepdegestrant were low grade (Grade 1-2) and the most common (=10%) adverse reactions, including laboratory abnormalities, 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, electrocardiogram QT prolonged, decreased platelets, and constipation. Arvinas and Pfizer intend to jointly identify and select a third-party partner with the capabilities and expertise to maximize the commercial potential of VEPPANU. The companies are on track to announce selection of a third party. VEPPANU is a prescription medicine to treat people with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced breast cancer or breast cancer that has spread to other parts of the body (metastatic), and whose disease has progressed after at least one line of endocrine-based therapy. Your healthcare provider will perform a test to make sure that VEPPANU is right for you. VEPPANU can cause serious side effects, including heart rhythm problems (QTc interval prolongation). VEPPANU can cause changes in the electrical activity of your heart and may increase your risk of abnormal heart rhythm problems, and sudden death. Your healthcare provider will check your heart with a test called an electrocardiogram (ECG) and check your blood potassium and magnesium levels before and as needed during treatment with VEPPANU. The most common side effects of VEPPANU include decreased white blood cell counts, decreased red blood cell counts, abnormal electrocardiogram (QT prolonged), nausea, increased liver function tests, muscle and bone pain, tiredness, decreased appetite, decreased platelet counts, decreased potassium levels in your blood, and constipation. Your healthcare provider may decrease your dose, temporarily stop, or completely stop treatment with VEPPANU, if you develop certain side effects. VEPPANU may affect fertility in males and in females who are able to become pregnant. The Phase 3 VERITAC-2 clinical trial (NCT05654623) is a global, randomized, open-label trial evaluating the efficacy and safety of vepdegestrant (ARV-471) as a monotherapy compared to fulvestrant in patients with ER+/HER2- advanced or metastatic breast cancer previously treated with a CDK4/6 inhibitor plus endocrine therapy. The trial enrolled 624 patients, 270 of whom had ESR1m positive disease, at 213 sites in 25 countries. Patients were randomized 1:1 to receive either vepdegestrant once daily, orally on a 28-day continuous dosing schedule, or fulvestrant, administered intramuscularly on Days 1 and 15 of Cycle 1 and then on Day 1 of each 28-day cycle starting from Day 1 of Cycle 2. In the trial, 43% of patients (n=270) had ESR1 mutations detected. The primary endpoint was progression-free survival (PFS) in the ESR1-mutation and intent-to-treat populations as determined by blinded independent central review. VEPPANU (vepdegestrant) is an orally bioavailable PROteolysis TArgeting Chimera (PROTAC), estrogen receptor degrader approved in the U.S. for use as a monotherapy in the treatment of adults with estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2-), ESR1-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy. In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will share worldwide development costs, commercialization expenses, and profits. In September 2025, Arvinas and Pfizer announced their plan to jointly select a third party for the commercialization and potential further development of vepdegestrant.
