Pfizer and Arvinas Abandon Commercialization of PROTAC Inhibitor, Triggering Layoffs and Pipeline Refocus

Pfizer and Arvinas have decided to out-license the commercialization rights for their PROTAC estrogen receptor degrader vepdegestrant (formerly ARV-471) to a third party, despite a recent FDA submission for its approval in ESR1-mutant, ER+/HER2- advanced or metastatic breast cancer35.

This decision follows mixed Phase 3 trial results that led to the discontinuation of two pivotal trials testing vepdegestrant in combination with Pfizer's CDK4/6 inhibitors25.

Arvinas is implementing additional layoffs, reducing its workforce by another 15%, focused mostly on roles associated with vepdegestrant commercialization, on top of the one-third reduction announced earlier in the year25.

The company expects to achieve approximately $100 million in annual cost savings compared to fiscal year 2024, extending its cash runway through the second half of 202835.

Arvinas' pipeline focus will now shift toward earlier-stage assets, including ARV-102 (LRRK2 degrader for Parkinson’s and PSP), ARV-393 (BCL6 degrader for non-Hodgkin lymphoma), and ARV-806 (KRAS G12D degrader for solid tumors)5.

Both companies stated that finding a capable third-party commercialization partner is the best way to unlock vepdegestrant’s value if approved, but the move is notable given the product's pending regulatory review35.

Sources:

2. https://www.fiercebiotech.com/biotech/arvinas-lays-33-staff-axes-pfizer-partnered-phase-3-trials-after-seeing-mixed-data

3. https://www.globenewswire.com/news-release/2025/09/17/3152028/0/en/Arvinas-Provides-Update-on-Collaboration-with-Pfizer-and-Announces-Further-Actions-to-Support-Value-Creation.html

5. https://www.fiercebiotech.com/biotech/pfizer-arvinas-lose-interest-commercializing-protac-inhibitor-leading-layoffs-biotech