FDA cleared Veppanu (vepdegestrant) on Friday, a month ahead of its June 5 PDUFA date, making the Pfizer-Arvinas collaboration the first to take a PROTAC therapy across the FDA finish line.
The approval covers adult patients with ER-positive, HER2-negative advanced or metastatic breast cancer carrying an ESR1 mutation, after at least one prior line of endocrine therapy. Arvinas has been developing the PROTAC protein degrader platform since 2013, and Veppanu is the company’s first approved product.
The path to approval wasn’t clean. In the Veritac-2 phase 3 study, Veppanu cut the risk of disease progression or death by 43% versus AstraZeneca’s Faslodex in ESR1-mutant patients, with median progression-free survival of 5 months versus 2.1 months on Faslodex. But the drug failed to improve PFS in the trial’s overall population, unselected for ESR1 mutation. Arvinas’s stock was halved on that news. The duo axed two phase 3 combination trials.
Up to 40-50% of ER-positive, HER2-negative breast cancer patients on endocrine therapy with a CDK4/6 inhibitor carry ESR1 mutations, according to Arvinas. Those patients face endocrine resistance and faster disease progression.
Don’t expect Pfizer or Arvinas to be selling Veppanu, though. In September, the pair outlined plans to out-license commercialization rights to a third party, calling it the “best path forward to unlock the full value of vepdegestrant.” A partner announcement is on track, Arvinas said Friday.
Arvinas shares climbed about 6% on the news. The original PDUFA date was June 5.
Sarah Chen