Vepdegestrant, sold under the brand name Veppanu, is an anti-cancer medication used for the treatment of breast cancer.[1][2] It is a heterobifunctional protein degrader.[1][2] It was developed by Arvinas and Pfizer.[3] It is taken by mouth.[1][2]

Vepdegestrant was approved for medical use in the United States in May 2026.[2]

Medical uses

Veppanu is indicated for the treatment of adults with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, 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.[1][2][4]

Adverse effects

The US prescribing information includes warnings and precautions for QTc interval prolongation and embryo-fetal toxicity.[1][2]

Mechanism of action

Vepdegestrant is designed as a PROTAC that recruits the ubiquitin-proteasome system to target the estrogen receptor for degradation.[5] The compound contains both an E3 ubiquitin ligase-binding moiety and an estrogen receptor-binding domain, intended to bring these proteins into proximity to trigger ubiquitination and subsequent proteasomal degradation of the ER protein.[6] In laboratory studies, vepdegestrant demonstrated ER degradation in ER-positive breast cancer cell lines with reported DC50 values of approximately 1-2 nM.[7]

History

Efficacy was evaluated in VERITAC-2 (NCT05654623), a randomized, open-label, active-controlled, multi-center trial in 624 adults with ER-positive, HER2-negative, advanced or metastatic breast cancer, of whom 270 had tumors carrying ESR1 mutations.[2] Participants were required to have disease progression on one to two lines of endocrine therapy, including one line with a CDK4/6 inhibitor.[2] Participants were randomized (1:1) to receive vepdegestrant orally once daily, or fulvestrant intramuscularly on days 1 and 15 of cycle 1 and then once monthly thereafter.[2] Randomization was stratified by ESR1 mutation status and visceral metastasis.[2] ESR1 mutational status was determined by blood circulating tumor deoxyribonucleic acid (ctDNA) using central or local testing.[2]

Phase I/II trials

Vepdegestrant has been evaluated in early-phase clinical trials as both monotherapy and in combination with other agents in patients with ER+/HER2- breast cancer. In a first-in-human Phase I/II study, vepdegestrant monotherapy was well tolerated and showed clinical activity in pretreated patients.[8]

Phase III VERITAC-2 trial

The Phase III VERITAC-2 trial (NCT05654623) is a randomized, open-label study comparing vepdegestrant to fulvestrant in patients with ER+/HER2- advanced breast cancer.[9] The trial enrolled 624 patients at sites in 26 countries who had previously received treatment with a CDK4/6 inhibitor plus endocrine therapy.[10]

In March 2025, results were announced from the VERITAC-2 trial. According to company statements, the study met its primary endpoint in the ESR1-mutant patient population, showing improvement in progression-free survival compared to fulvestrant.[10] However, the trial did not achieve statistical significance in the overall intent-to-treat population.[11] Detailed results were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.[12]

Preclinical studies

In preclinical studies, vepdegestrant achieved greater ER degradation in vivo compared with fulvestrant, which correlated with improved tumor growth inhibition (TGI).[13] The compound showed high efficacy as monotherapy and demonstrated synergistic effects when combined with CDK4/6 inhibitors or PI3K/mTOR pathway inhibitors in preclinical ER+ breast cancer models.[13]

Society and culture

The US Food and Drug Administration (FDA) granted fast track designation to vepdegestrant in February 2024, as a monotherapy for the treatment of adults with ER+/HER2- metastatic breast cancer.[14][15]

Vepdegestrant was approved for medical use in the United States in May 2026.[2][16]

Names

Vepdegestrant is the international nonproprietary name.[17]

Vepdegestrant is sold under the brand name Veppanu.[2]

References

  1. 1 2 3 4 5 6 "Veppanu (vepdegestrant) tablets, for oral use" (PDF). arvinas.com. Retrieved 6 May 2026.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 "FDA approves vepdegestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer". U.S. Food and Drug Administration (FDA). 1 May 2026. Retrieved 5 May 2026. Public Domain This article incorporates text from this source, which is in the public domain.
  3. ↑ "Arvinas, Pfizer reworking partnership on 'Protac' cancer drug". BioPharma Dive. Retrieved 17 September 2025.
  4. ↑ "Novel Drug Approvals for 2026". U.S. Food and Drug Administration (FDA). 1 May 2026. Retrieved 5 May 2026. Public Domain This article incorporates text from this source, which is in the public domain.
  5. ↑ "Estrogen Receptor". Arvinas. Retrieved 17 September 2025.
  6. ↑ Sakamoto, Kathryn M.; Kim, Kwon B.; Kumagai, Ayumu; Mercurio, Frank; Crews, Craig M.; Deshaies, Raymond J. (18 January 2022). "PROTAC targeted protein degraders: the past is prologue". Nature Reviews Drug Discovery. 21 (3): 181–200. doi:10.1038/s41573-021-00371-6. PMC 8765495. PMID 35046570.
  7. ↑ "Vepdegestrant (ARV-471) PROTAC ER Degrader". MedChemExpress. Retrieved 17 September 2025.
  8. ↑ Hamilton, Erika P.; Ma, Cynthia; De Laurentiis, Michelino; Iwata, Hiroji; Hurvitz, Sara A.; Wander, Seth A.; et al. (2024). "VERITAC-2: a Phase III study of vepdegestrant, a PROTAC ER degrader, versus fulvestrant in ER+/HER2- advanced breast cancer". Future Oncology (London, England). 20 (32): 2447–2455. doi:10.1080/14796694.2024.2377530. ISSN 1744-8301. PMC 11524203. PMID 39072356.
  9. ↑ "A Study to Compare the Efficacy and Safety of Vepdegestrant (ARV-471) Versus Fulvestrant in Participants With Estrogen Receptor-positive, HER2-negative Advanced Breast Cancer (VERITAC-2)". ClinicalTrials.gov. 30 June 2025. Retrieved 17 September 2025.
  10. 1 2 "Arvinas and Pfizer Announce Positive Topline Results from Phase 3 VERITAC-2 Clinical Trial". Arvinas. Retrieved 17 September 2025.
  11. ↑ "VERITAC-2 Trial Shows Vepdegestrant Significantly Improves Survival in ESR1-Mutant Breast Cancer". Applied Clinical Trials Online. 24 March 2025. Retrieved 17 September 2025.
  12. ↑ "Arvinas Announces Results from the VERITAC-2 Trial Selected as Late-Breaking Oral Presentation at the 2025 ASCO Annual Meeting". Arvinas. 23 April 2025. Retrieved 17 September 2025.
  13. 1 2 Gough, Sheryl M.; Flanagan, John J.; Teh, Jimmy (15 August 2024). "Oral Estrogen Receptor PROTAC Vepdegestrant (ARV-471) Is Highly Efficacious as Monotherapy and in Combination with CDK4/6 or PI3K/mTOR Pathway Inhibitors in Preclinical ER+ Breast Cancer Models". Clinical Cancer Research. 30 (16): 3549–3562. doi:10.1158/1078-0432.CCR-23-3465. PMC 11325148. PMID 38819400.
  14. ↑ "FDA Grants Fast Track Status to Vepdegestrant for ER+/HER2– Metastatic Breast Cancer". Oncology Live. 6 February 2024. Retrieved 17 September 2025.
  15. ↑ "Vepdegestrant Gains FDA Fast Track Designation in ER+/HER2- Breast Cancer". Targeted Oncology. 6 February 2024. Retrieved 17 September 2025.
  16. ↑ "Arvinas Announces FDA Approval of Veppanu (vepdegestrant) for the Treatment of ESR1m, ER+/HER2- Advanced Breast Cancer". Arvinas (Press release). Retrieved 5 May 2026.
  17. ↑ World Health Organization (2023). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 89". WHO Drug Information. 37 (1). hdl:10665/366661.

Further reading

  • Clinical trial number NCT05654623 for "A Study to Learn About a New Medicine Called Vepdegestrant (ARV-471, PF-07850327) in People Who Have Advanced Metastatic Breast Cancer (VERITAC-2)" at ClinicalTrials.gov
source: https://en.wikipedia.org/wiki/Vepdegestrant