Long-term vatiquinone treatment slows FA disease progression relative to FACOMS Natural History

Topic:

Clinical Trials

Poster Number: O183

Author(s):

Jonathan Cherry, PhD, PTC Therapeutics, Inc., 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, Katherine Mathews, MD, 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, SH Subramony, MD, University of Florida, Richard Roxburgh, PhD, FRACP, Neurogenetics Clinic Centre for Brain Research, University of Auckland, Mark Rance, PTC Therapeutics, Inc., Olivia Zhang, PhD, PTC Therapeutics, Inc., Lee Golden, MD, PTC Therapeutics, Inc., David Lynch, MD, PhD, Children's Hospital of Philadelphia, Theresa Zesiewicz, MD, FAAN, University of South Florida

Background/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. Here, we report long-term 36-month results from the MOVE-FA extension study and 24-month results from Study EPI-2010-006 compared to matched natural history cohorts from FACOMS (Friedreich Ataxia Clinical Outcome Measures).

Methods: MOVE-FA (NCT04577352), a global phase 3 study, evaluated the safety and efficacy of vatiquinone in patients with FA. Participants that completed MOVE-FA were eligible to rollover into the long-term extension study (NCT05515536). MOVE-FA included 143 participants with FA aged ≥7 years (mean age: 18.7).

EPI-2010-006 (NCT01728064) was a phase 2 study that examined the effects of EPI-743 on neurologic function in adult patients with FA. Sixty-three participants aged ≥18 years (mean age: 28.9) were enrolled.

The pre-specified primary endpoint for these analyses was the modified Friedreich Ataxia Rating Scale (mFARS).

Results: After 36 months in the MOVE-FA long-term extension study, participants in the treatment group demonstrated a 3.75-point increase in mFARS. The matched FACOMS cohort progressed by 7.48-points over the same period. Vatiquinone treatment resulted in a 3.7-point benefit (p<0.0001, N=70) in mFARS relative to FACOMS. This treatment difference on the primary endpoint represents a clinically meaningful 50% slowing of disease progression over 3 years. Following 24-months of treatment with vatiquinone in EPI-2010-006, treated participants demonstrated a 0.92-point decrease in mFARS while participants in the matched FACOMS cohort progressed by 3.89-points. This resulted in a 4.8-point treatment benefit (p<0.0001, N=41), consistent with a 2-year delay in progression. Conclusions: The results of the extension studies provide further evidence of the potential benefit of vatiquinone for the treatment of FA. The pre-specified endpoints for two different long-term extension studies were met, with highly statistically significant evidence of durable treatment benefit in slowing disease progression in pediatric and adult patients.