Improvement in Upright Stability subscale of mFARS with Vatiquinone Treatment in MOVE-FA: a Phase 3, Double-blind, Placebo-controlled Trial


Clinical Trials

Poster Number: S80


David Lynch, MD, PhD, Children's Hospital of Philadelphia, Antoine Duquette, MD, MSc, FRCP(C), Centre Hospitalier de l'Universite de Montreal, Marcondes Cavalcante França Jr, MD, PhD, University of Campinas (UNICAMP), Susan Perlman, MD, University of California, Los Angeles, Alexandra Durr, MD, PhD, Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, APHP, Enrico Bertini, MD, Ospedale Pediatrico Bambino Gesu’ IRCCS, Alejandra Darling, MD, PhD, Hospital Sant Joan de Déu, Katherine Mathews, MD, FAAN, University of Iowa, Ludger Schöls, MD, University Hospital of Tübingen, Anne Fournier, MD, FRCPC, FACC, FHRS, FCCS, CHU Sainte-Justine, Martin Delatycki, MD, PhD, Murdoch Children's Research Institute, S H Subramony, M.D., Univsersity of Florida, Fixel Center for Neurological Disorders, Richard Roxburgh, PhD, FRACP, Neurogenetics Clinic Centre for Brain Research, University of Auckland, Auckland, NZ, Olivia Zhang, PhD, PTC Therapeutics, Inc., Christian Rummey, PhD, Clinical Data Science GmbH, Alana Salvucci, DO, PTC Therapeutics, Inc., Bert Yao, MD, PhD, MHS, PTC Therapeutics, Inc., Jonathan Cherry, PhD, PTC Therapeutics, Lee Golden, MD, PTC Therapeutics, Inc., Theresa Zesiewicz, MD, FAAN, University of South Florida

Background and Objectives: Friedreich Ataxia (FA) is characterized by progressive neurological damage and loss of ambulation. Vatiquinone is an oral, first-in-class inhibitor of 15-lipoxygenase. MOVE-FA (NCT04577352), a global phase 3 trial, evaluated vatiquinone safety and efficacy in patients with FA. The Upright Stability subscale (USS, or FARS E) is the axial component of the modified FA Rating Scale (mFARS) that assesses functions related to balance, stance, and mobility. Analysis of natural history data shows that disease progression in ambulatory pediatric and adolescent FA patients is primarily driven by declines in the functions assessed in the USS.

Methods: The study enrolled 143 subjects with FA aged ≥7 years, mFARS score of 20–70, and the ability to ambulate ≥10 feet in 1 minute. The primary endpoint was placebo corrected change from baseline in mFARS at 72-weeks. The Intent-to-Treat (ITT) population had a mean age of 18.7 and the primary analysis population modified ITT (mITT) included 123 subjects 7-21 years (mean 14.6). USS was collected as part of mFARS, the primary endpoint.

Results: In the placebo population, of the four subscales of mFARS, USS is the only one to demonstrate progression from baseline to week 72, consistent with natural history data. Significant benefit was recorded in USS (-1.26 [p=0.021]) in the mITT population. Vatiquinone treatment also delayed the loss of functional milestones represented by individual items within the USS, specifically items E2B (feet apart eyes closed) and E3A (feet together eyes open). Comparison of rate of disease progression in USS predicted a 42% reduction in disease progression per year in the vatiquinone-treated group.

Conclusions: Vatiquinone treatment resulted in clinically meaningful and statistically significant treatment effects on the USS, a sensitive and predictive endpoint for risk of loss of ambulation, prevention of which is a key goal for therapy in ambulatory FA patients.