Mixed pivotal data for Pfizer, Arvinas’ protein degrader in breast cancer
Pfizer and Arvinas have announced mixed results from their Phase 3 VERITAC-2 trial evaluating vepdegestrant, an investigational oral PROTAC (PROteolysis TArgeting Chimera) estrogen receptor (ER) degrader, for the treatment of advanced or metastatic breast cancer13.
Key Findings
- Primary Endpoint:
The trial met its primary endpoint in the estrogen receptor 1-mutant (ESR1m) population, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to fulvestrant3.
- Intent-to-Treat Population:
The trial did not reach statistical significance in improvement in PFS in the overall intent-to-treat (ITT) population13.
- Safety Profile:
Vepdegestrant was generally well tolerated, with a safety profile consistent with previous studies3.
Significance
- Vepdegestrant is the first PROTAC degrader to demonstrate clinical benefit in a Phase 3 trial3.
- The drug showed potential efficacy in patients with ESR1 mutations, which are found in approximately 40% of patients in the second-line setting3.
Impact and Future Steps
- Arvinas' stock dropped significantly (43-50%) following the announcement, reflecting investor disappointment in the mixed results15.
- Detailed results will be presented at a medical conference later in 20253.
- Data will be shared with global regulatory authorities to potentially support regulatory filings3.
- The trial will continue to assess overall survival as a key secondary endpoint3.
Market Implications
The failure to show significant improvement in the wild-type population may limit vepdegestrant's market opportunities. BMO Capital Markets analysts estimate this could represent a loss of up to $4 billion in potential revenue across treatment lines1.
While the results are mixed, Pfizer and Arvinas remain optimistic about vepdegestrant's potential to provide meaningful outcomes for patients with metastatic breast cancer harboring ESR1 mutations13.
Sources:
1. https://www.biospace.com/drug-development/pfizer-arvinas-post-mixed-late-stage-breast-cancer-data-for-closely-watched-protac-drug
3. https://www.globenewswire.com/news-release/2025/03/11/3040386/0/en/Arvinas-and-Pfizer-Announce-Positive-Topline-Results-from-Phase-3-VERITAC-2-Clinical-Trial.html
5. https://www.fiercebiotech.com/biotech/pfizer-arvinas-hormone-therapy-posts-mixed-survival-results-first-phase-3-test