Arvinas, in partnership with Pfizer, has received US regulatory approval for Veppanu (vepdegestrant), the first proteolysis targeting chimera (PROTAC) therapy to reach the market. The first-in-class drug is approved for the treatment of postmenopausal women and men with ESR1-mutated, ER+/HER2- advanced or metastatic breast cancer whose disease has progressed on prior endocrine-based therapy. Vepdegestrant is an oral therapy designed to induce the degradation of both wild-type and mutant estrogen receptors. Pfizer licensed global rights to the candidate in July 2021 in a deal valued at up to USD 2.05 billion.

Approval is based on positive data from the Phase III VERITAC-2 trial. While the therapy did not demonstrate a statistically significant improvement in progression-free survival (PFS) in the overall study population, it achieved a clinically meaningful benefit in the pre-specified ESR1-mutant subgroup, nearly doubling median PFS compared to fulvestrant (5.0 months vs 2.1 months). The safety profile was manageable, with the most common adverse events being fatigue, elevated liver enzymes, and nausea. Overall survival data remain immature.

PharmCube's NextBiopharm® database lists over 1,000 PROTAC candidates under development, mostly in preclinical stage. Click here to request a free trial for NextBiopharm®.