Pfizer and Arvinas have axed two phase 3 trials from their estrogen receptor (ER) degrader R&D plan in the wake of mixed data. Arvinas disclosed the rethink alongside news that it is laying off one-third of its staff to cut costs and extend its cash runway.
The partners reported the failure of PROteolysis TArgeting Chimera (PROTAC) ER degrader vepdegestrant to improve progression-free survival in breast cancer patients in March. However, with the trial showing patients with ESR1 mutations responded to treatment, Pfizer and Arvinas touted the results as positive and set out plans to share the phase 3 data with regulators.
Thursday, Arvinas shared an update on the program as part of its first-quarter results. The partners have removed a first-line phase 3 trial of vepdegestrant and Pfizer’s investigational CDK4 inhibitor atirmociclib from their plan. A second-line phase 3 trial pairing vepdegestrant with a CDK4/6 inhibitor has also ended up on the cutting room floor. Arvinas CEO John Houston, Ph.D., explained the thinking behind the shifts.
“Based on recent discussions with health authorities and our observations from other trials involving biomarker-selected populations, we believe ER therapies will be restricted to patients with ESR1 mutations in the second line-plus setting,” Houston said on an earnings call. “We and Pfizer will continue to evaluate our ongoing combination studies in the second line-plus setting.”
Houston said Arvinas will make data-driven decisions about whether further investment in combinations is warranted as trials wrap up. Citing “recent challenges in the capital markets,” Houston said the biotech is rethinking spending to ensure its current cash reserves can take its programs to data milestones.
Arvinas is laying off 33% of its employees. The biotech had 430 full-time employees at the end of last year. Houston said the layoffs, coupled with a portfolio reprioritization, will save about $80 million. Over three years, the CEO put total cost savings and cost avoidance at $500 million. The biotech ended March with $954.3 million. Arvinas forecast the changes will extend its cash runway into the second half of 2028. Under the previous plan, the biotech said it had the cash to fund operations into 2027.
Arvinas and Pfizer are preparing to submit vepdegestrant for approval as a second-line monotherapy in the second half of the year. Houston said about 25,000 ESR1-mutant patients start second-line treatment a year. Drugs such as Stemline Therapeutics’ Orserdu already serve the population, but Houston said they are likely capturing around one-third of the market, leaving a significant opportunity for vepdegestrant.