Veppanu, the first PROTAC therapy approved by the FDA, improved progression free survival by 43% versus AstraZeneca’s Faslodex but showed no such significant benefit in the intention-to-treat analysis.
The FDA on Friday greenlit Pfizer and Arvinas’ protein degrader Veppanu for the treatment of certain types of breast cancer as the first-ever PROTAC therapy. Results from the Phase 3 VERITAC-2 study paved the way for Veppanu’s approval, despite mixed topline data in March last year.
Short for proteolysis-targeting chimeras, these drugs actively target and destroy disease-causing molecules. Veppanu, formerly known as vepdegestrant, is specifically indicated for patients with advanced or metastatic ER-positive and HER2-negative breast cancer who also harbor mutations in the ESR1 gene. Only those who have progressed after a prior line of endocrine therapy are eligible for Veppanu.
As a PROTAC, Veppanu is a small-molecule drug that has two different functional sites, one of which binds to the estrogen receptor and the other to a protein that can trigger the cell’s targeted degradation pathway. This structure leads to widespread degradation of estrogen receptors, in turn disrupting cancer cells’ ability to proliferate.
Pfizer and Arvinas did not present specific VERITAC-2 data in March, only noting that the drug elicited a “statistically significant and clinically meaningful” progression-free survival (PFS) benefit versus AstraZeneca’s Faslodex. However, in the intent-to-treat (ITT) analysis, which covers all patients who were randomized, Veppanu showed no significant PFS effect.
A follow-up readout in June that year showed a 43% reduction in the risk of disease progression or death in patients on Veppanu versus Faslodex. The ITT analysis again failed to hit statistical significance. Overall survival data was immature at the time of filing, according to Arvinas’ Friday release.
As for safety, Veppanu’s label does not carry a boxed warning but does alert patients and prescribers to heart rhythm abnormalities and embryo-fetal toxicities.
Veppanu was originally developed by Arvinas. Pfizer bought into the drug in July 2021 with $650 million upfront, a $350 million equity investment and the promise of up to $1.4 billion in milestones.
It is yet unclear when Veppanu will hit U.S. shelves—Pfizer and Arvinas will first need to select a third-party commercialization partner for the drug. The companies say they are “on track” to identify this partner but have not yet provided a specific timeline.
Veppanu marks Arvinas’ first FDA approval, though there remain “questions around commercialization given ARVN has not yet announced a partner,” analysts at Truist Securities wrote to investors in a Friday note. The firm forecasts $1.1 billion in peak sales for the drug in 2036.
