Investigational Vatiquinone Slows Friedreich Ataxia Disease Progression Relative to FACOMS Natural History Cohort

Author(s):

Two separate long-term extension studies met their pre-specified endpoints, showing highly significant evidence of sustained treatment benefits in slowing disease progression in pediatric and adult patients.

Theresa Zesiewicz, MD

In a new comparative analysis, results showed that treatment with vatiquinone (PTC Therapeutics), an investigational agent in development for Friedreich ataxia (FA), resulted in significantly slower disease progression in individuals with FA relative to the Friedreich Ataxia Clinical Outcomes Measures (FACOMS) natural history cohort. Overall, the results of these findings provide further evidence of the potential benefit of vatiquinone, which remains currently under review by the FDA.

Presented at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific conference, held March 16-19, in Dallas, Texas, investigators reported 36-month results from the MOVE-FA extension and 24-month results from Study EPI-2010-006 (NCT01728064) compared with natural history cohorts from FACOMS. For context, MOVE-FA, a global phase 3 study (NCT045773252), evaluated the safety and efficacy of vatiquinone in 143 patients with FA at least 7 years of age. Those completing MOVE-FA could roll over into the long-term extension, while EPI-2010-006, a phase 2 study, assessed the effects of vatiquinone, formerly known as EPI-743, on neurologic function in 63 adults with FA aged at least 18.

In the MOVE-FA long-term extension, vatiquinone-treated patients showed a 3.75-point increase in modified Friedreich Ataxia Rating Scale (mFARS) score after 36 months whereas those in the matched FACOMS cohort progressed by 7.48-points over the same period. All told, vatiquinone treatment showed a clinically meaningful 50% slowing of disease progression over 3 years, with a 3.7-point benefit in mFARS (P <0.0001, n = 70) relative to FACOMS.

Led by Theresa Zesiewicz, MD, director of the Ataxia Research Center at the University of South Florida, vatiquinone-treated patients demonstrated a 0.92-point decrease in mFARS after 24 months in EPI-2010-006. For comparison, those in the matched FACOMS cohort progressed by 3.89-points, resulting in a 4.8-point treatment benefit (P <.0001; n = 41) between the 2 groups, consistent with a 2-year delay in progression.

Zesiewicz also had a hand in the conduct of EPI-2010-006, a multicenter trial that evaluated EPI-743 during a 6-month controlled phase, followed by an 18-month open-label extension. Published in 2018, results from the study showed that EPI-743 was safe and well tolerated, with no significant improvements in key end points during the placebo phase. Despite this, investigators did observe statistically significant improvements in neurological function and disease progression relative to a natural history cohort after 24 months of treatment (P <.001).²

The FDA is expected to give a decision on vatiquinone by August 19, 2025, the scheduled PDUFA date. Its new drug application (NDA), accepted last month, was based on findings from MOVE-FA, as well as 2 long-term trials that featured pediatric and adult patients with FA. MOVE-FA, a registration-directed trial, did not meet its primary end point of change in overall mFARS (P = .14); however, there was a statistically significant effect (P = .021) observed on the mFARS upright stability subscale, a pre-specified end point (P <.0001; n = 70).³

Currently, omaveloxolone (Skyclarys; Biogen) is the only FDA-approved treatment for FA in patients aged 16 and older. While omaveloxolone functions as an antioxidant and Nrf2 activator, vatiquinone is a first-in-class selective inhibitor of 15-LO, an enzyme critical to the disrupted energetic and oxidative stress pathways in FA. Additionally, off-label treatments like idebenone, coenzyme Q10, and vitamin E have been used to address symptoms or underlying disease mechanisms.

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REFERENCES
1. Cherry J, Duquette A, Perlman S, et al. Long-term vatiquinone treatment slows FA disease progression relative to FACOMS Natural History. Presented at: 2025 Clinical & Scientific conference; March 16-19. Dallas, TX. Abstract 0183.
2. Zesiewicz T, Salemi JL, Perlman S, et al. Double-blind, Randomized and Controlled Trial of EPI-743 in Friedreich’s Ataxia. Neurodegenerative Diseas Manag. 2018;8(4):233-242. doi: 10.2217/nmt-2018-0013.
3. PTC Therapeutics announces topline results from vatiquinone MOVE-FA registration-directed trial. News release. May 23, 2023. Accessed March 18, 2025. https://www.prnewswire.com/news-releases/ptc-therapeutics-announces-topline-results-from-vatiquinone-move-fa-registration-directed-trial-301832658.html