Arvinas and Pfizer are the first to take a PROteolysis TArgeting Chimera (PROTAC) therapy across the FDA finish line, opening the door to a new option for certain breast cancer patients. However, the duo won’t be involved past that, as the companies have been scouting for a new partner to commercialize the drug following lackluster clinical data.
The med, called Veppanu (vepdegestrant), has won approval to treat adult patients with ER-positive, HER2-negative advanced or metastatic breast cancer with an estrogen receptor 1 mutation following at least one line of endocrine therapy. The nod arrived a month ahead of the FDA’s planned June 5 decision date.
Veppanu is a PROTAC, a type of protein degrader that Arvinas has been pioneering since 2013, CEO Randy Teel, Ph.D., said in a company press release.
“This milestone demonstrates that targeted protein degradation can translate into meaningful clinical impact,” Teel explained. “It also strengthens our confidence in the breadth and versatility of our exciting clinical pipeline across oncology, neurodegenerative, and neuromuscular diseases.”
The drug is Arvinas’ first approved product, but when it comes to commercialization, the company and its Big Pharma partner are taking their hands off the wheel. The duo in September outlined plans to out-license commercialization rights to the drug to a third party, figuring that to be the “best path forward to unlock the full value of vepdegestrant.”
The two are “on track” to announce their pick, Arvinas noted in its release Friday.
The FDA’s validation of Veppanu comes after some uncertainty around the drug’s development path that caused the partners to narrow their focus.
A mixed bag came out of the companies’ Veritac-2 phase 3 trial, which pit Veppanu against AstraZeneca’s standard of care Faslodex. Among patients with an ESR1 mutation, the drug proved it could reduce the risk of disease progression or death by 43% compared to Faslodex, with a median progression-free survival of 5 months versus Faslodex’s 2.1 months.
However, Veppanu failed to improve progression-free survival in the trial’s overall population unselected for ESR1. Arvinas’s stock price was halved on the back of the news at the time. And the pair axed two phase three trials that had tested Veppanu in combination therapies.
Discussions with health regulators confirmed that the therapy would likely be restricted to patients with the specific mutations in the second-line setting, former Arvinas CEO John Houston, Ph.D., previously said.
Still, the approval marks an important milestone for the patient community, Arvinas’ chief medical officer, Noah Berkowitz, M.D., Ph.D., commented in the company’s release Friday.
Up to 40% to 50% of ER-positive, HER2-negative breast cancer patients who are treated with endocrine therapy and a CDK4/6 inhibitor have ESR1 mutations, leading to endocrine resistance and faster disease progression, according to Arvinas.
The approval sent Arvinas’ share price up about 6% at the time of publication on Friday afternoon.
