Having already stripped back their development plans for the estrogen receptor (ER) degrader vepdegestrant on the back of mixed data, Pfizer and Arvinas have now decided to wash their hands of the drug.
Despite the two companies having submitted the oral PROteolysis TArgeting Chimera (PROTAC) ER degrader to the FDA for approval only last month, Pfizer and Arvinas have “jointly agreed to out-license the commercialization rights to vepdegestrant to a third party,” they announced in a Sept. 17 release.
The potential partner has yet to be identified, but Arvinas said the ideal applicant would have “capabilities and expertise to maximize the commercial potential of vepdegestrant, if approved, for patients with ESR1-mutant, ER+/HER2- advanced or metastatic breast cancer and potentially develop vepdegestrant in new settings.”
While it’s an unusual move for a Big Pharma to seek a commercialization partner for a drug that is already being considered for approval by the FDA, the decision won’t come as a shock for keen Arvinas observers.
Back in May, Pfizer and Arvinas axed two phase 3 trials—testing vepdegestrant with Pfizer’s investigational CDK4 inhibitor atirmociclib or with a CDK4/6 inhibitor, respectively—in the wake of mixed data.
At the time, Arvinas CEO John Houston, Ph.D., explained that discussions with health authorities had led the biotech to believe that the success of ER therapies “will be restricted to patients with ESR1 mutations in the second line-plus setting.”
As a result, Arvinas and Pfizer narrowed their focus to vepdegestrant’s potential as a second-line monotherapy, which was the indication requested in the FDA approval application. Houston also alluded to a need for the company to rethink its spending last year, and the strategic shift was accompanied by laying off about a third of the biotech’s workforce.
Fast-forward to yesterday, and both companies had come to the same conclusion that “finding a third-party commercial partner is the best path forward to unlock the full value of vepdegestrant and ensure vepdegestrant is available promptly if approved for use by regulatory authorities.”
“Today’s announcement further supports our goal to bring vepdegestrant to patients and we are confident that vepdegestrant’s differentiated profile will attract interest from potential partners seeking to strengthen their oncology portfolios,” Houston said in the release. “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’ attention will now turn to its less advanced pipeline of three phase 1-stage PROTAC degraders. They include ARV-102, an LRRK2 degrader being assessed for progressive supranuclear palsy and Parkinson’s disease, as well as ARV-393, a BCL6 degrader being tested for non-Hodgkin lymphoma. There’s also ARV-806, a KRAS G12D degrader for solid tumor malignancies.
The latest strategic pivot means more layoffs are in store for Arvinas’ workforce, with the number of employees to be reduced by a further 15%, primarily among roles related to vepdegestrant commercialization.
Combined with the previously announced cost-saving measures from May and the potential payday if a new partner is found for vepdegestrant, Arvinas expects to reduce its year-on-year spend in 2025 by about $100 million.