Pfizer and Arvinas Shift Strategy on PROTAC Inhibitor, Seek Third-Party Commercialization

Pfizer and Arvinas have announced a significant change in their approach to the commercialization of vepdegestrant, their jointly developed oral PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader. The companies have decided to out-license the commercialization rights to a third party, despite having submitted the drug to the FDA for approval just last month.

Decision Follows Mixed Data and Strategic Realignment

The move comes in the wake of mixed clinical data that led to the cancellation of two phase 3 trials in May. These trials were testing vepdegestrant in combination with Pfizer's investigational CDK4 inhibitor atirmociclib and with a CDK4/6 inhibitor, respectively. Following discussions with health authorities, Arvinas CEO John Houston, Ph.D., explained that the success of ER therapies is likely to be "restricted to patients with ESR1 mutations in the second line-plus setting."

As a result, both companies narrowed their focus to vepdegestrant's potential as a second-line monotherapy, which is the indication requested in the recent FDA approval application. This strategic shift was accompanied by significant workforce reductions at Arvinas, with about a third of the biotech's employees laid off earlier this year.

Seeking a New Commercial Partner

Pfizer and Arvinas are now actively seeking a third-party commercial partner to "maximize the commercial potential of vepdegestrant." The ideal candidate would have the capabilities and expertise to not only commercialize the drug for patients with ESR1-mutant, ER+/HER2- advanced or metastatic breast cancer but also potentially develop vepdegestrant in new settings.

John Houston emphasized the company's confidence in vepdegestrant's differentiated profile, stating, "We are confident that vepdegestrant's differentiated profile will attract interest from potential partners seeking to strengthen their oncology portfolios." He added, "We and Pfizer remain committed to the metastatic breast cancer community and believe vepdegestrant has the potential to be a best-in-class therapeutic option in the second-line ESR1 mutant setting."

Arvinas Refocuses on Early-Stage Pipeline

With this strategic pivot, Arvinas will now turn its attention to its less advanced pipeline of three phase 1-stage PROTAC degraders:

1. ARV-102: An LRRK2 degrader being assessed for progressive supranuclear palsy and Parkinson's disease
2. ARV-393: A BCL6 degrader being tested for non-Hodgkin lymphoma
3. ARV-806: A KRAS G12D degrader for solid tumor malignancies

This refocusing of efforts will result in further workforce reductions at Arvinas, with an additional 15% of employees to be laid off, primarily in roles related to vepdegestrant commercialization. The company expects these measures, combined with the potential revenue from a new vepdegestrant partner, to reduce its year-on-year spend in 2025 by approximately $100 million.