**Arvinas and Pfizer Search for New Collaborator for Vepdegestrant as Market Obstacles Arise**
Arvinas and Pfizer, the joint developers of the groundbreaking bifunctional protein degrader vepdegestrant, are on the lookout for a new collaborator to successfully launch the medication in the market. Although clinical trials have validated the efficacy of vepdegestrant, it has not outperformed current therapies, prompting strategic changes. They have submitted an application for FDA approval, with a ruling expected by June 2026. Nonetheless, Arvinas is reducing its workforce by 15%, following a previous 30% cut disclosed in May and the scrapping of two phase 3 trial initiatives.
Bifunctional degraders, in contrast to conventional small-molecule inhibitors, leverage the body’s protein recycling mechanisms. Vepdegestrant primarily focuses on mutated estrogen receptors, utilizing E3 ubiquitin ligase enzymes to enable proteasomal degradation. It encounters rivalry from well-established SERD drugs such as AstraZeneca’s fulvestrant, which also promotes receptor degradation but is restricted to certain estrogen receptor mutations.
Initially regarded as a potential blockbuster for extensive use, vepdegestrant has demonstrated superiority over fulvestrant only in patients exhibiting specific ESR1 mutations, according to Glenda Walker, an oncology authority at Clarivate. This constraints its current applicability, although it may receive FDA authorization for ESR1 mutation-positive individuals who have experienced prior hormone therapies.
Walker indicates that the most favorable market introduction for vepdegestrant could be as a first-line treatment in combination therapies, requiring new phase 3 trials and alliances that can facilitate this advancement. In the meantime, Eli Lilly’s Inluriyo, another orally administered SERD, has achieved FDA approval, intensifying market competition.
Zoran Rankovic from the Institute of Cancer Research commends the drug’s development, deeming its swift progress in targeted protein degradation extraordinary. Rankovic believes vepdegestrant represents a bright future for this new category of treatments, potentially revolutionizing approaches to disease management.