Vatiquinone (DB11917): A Comprehensive Monograph on a First-in-Class 15-Lipoxygenase Inhibitor for Neurodegenerative Disease

Executive Summary

Vatiquinone (DrugBank ID: DB11917) is an orally bioavailable, investigational small molecule therapeutic developed by PTC Therapeutics as a potential treatment for rare neurodegenerative and mitochondrial disorders. Chemically identified as a synthetic analog of vitamin E and a para-benzoquinone, Vatiquinone represents a first-in-class selective inhibitor of the enzyme 15-lipoxygenase (15-LO). Its primary mechanism of action is the modulation of critical pathways involved in oxidative stress, neuroinflammation, and a specific form of iron-dependent programmed cell death known as ferroptosis. By targeting 15-LO, Vatiquinone aims to mitigate the downstream pathological consequences of mitochondrial dysfunction, particularly the lipid peroxidation that drives neuronal cell death in diseases characterized by high levels of oxidative stress.

The principal clinical development program for Vatiquinone has focused on Friedreich's ataxia (FA), a rare, progressive, and life-shortening neuromuscular disorder for which there is a significant unmet medical need, especially in pediatric populations. The cornerstone of its regulatory submission was the pivotal Phase 3 MOVE-FA trial. The trial yielded a complex and challenging set of results: it failed to meet its prespecified primary endpoint of a statistically significant change in the overall modified Friedreich Ataxia Rating Scale (mFARS) score. However, the study did demonstrate a statistically significant and clinically meaningful benefit on the prespecified mFARS Upright Stability Subscale (USS), a key measure of disease progression in the younger, ambulatory FA patient population.