Vatiquinone Shows Additional Benefits on Friedreich Ataxia Disease Progression Despite Failing to Meet Primary End Point


Over a 72-week treatment period, vatiquinone showed significant impacts on bulbar and upright stability subscales of the modified Friedreich Ataxia Rating Scale score.

Matthew B. Klein, MD, chief executive officer, PTC Therapeutics

Matthew B. Klein, MD

Newly reported topline findings from the phase 3 MOVE-FA study (NCT04577352) showed that treatment with vatiquinone (PTC Therapeutics), an agent in development for Friedreich ataxia (FA), did not meet its primary end point; however, the therapy did show positive benefit on other key disease subscales and secondary end points.1

MOVE-FA was a randomized, placebo-controlled study that enrolled 146 pediatric and adult patients with FA, a majority of which were under 18 years of age, and assessed the impact of vatiquinone over a 72-week period. Vatiquinone is a small molecule, first-in-class inhibitor of 15-Lipoxygenase (15-LO), an enzyme that is a key regulator of the energetic and oxidative stress pathways that are disrupted in FA. Prior to the study, the agent had shown an impact on mortality risk and a number of neurological and neuromuscular disease symptoms.

In total, after a the 72-week treatment period, investigators documented a mean placebo-corrected change in modified Friedreich Ataxia Rating Scale (mFARS) score, the primary end point, of 1.6 (P = .14). Despite this, patients on the agent showed significant benefits in the bulbar and upright stability subscales (P = .044 and P = .021), considered reflective of key aspects of disease morbidity and predict of loss of time to loss of ambulation.

"While we are disappointed that the study did not achieve its primary endpoint, we are encouraged by the findings of meaningful impact on several different aspects of FA disease progression and morbidity over 72 weeks,” Matthew B. Klein, MD, chief executive officer, PTC Therapeutics, said in a statement.1 "Given the signals of clinical benefit, vatiquinone's well-established safety profile in children, and the unmet medical need for pediatric patients with FA, we look forward to discussing a potential path to registration with regulatory authorities."

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Omaveloxolone (Skyclarys; Reata Pharmacueticals), approved earlier this year, stands as the only FDA-approved therapy to treat FA. In addition to showing effects on disease progression and mortality, treatment with vatiquinone resulted in statistically significant difference on the Modified Fatigue Scale, a measure of disease morbidity (P = .025). For individuals who completed the 72-week treatment program, a prespecified analysis showed a placebo-corrected difference of 2.31, or a 75% slowing of disease progression. Above all, the therapy continued to show a safe profile that was consistent with previous studies.

Prior to MOVE-FA, vatiquinone previously demonstrated a statistically significant effect on disease severity in a phase 2 trial (NCT01962363). The small-scale study, which featured 4 individuals with FA, showed that after 6 months of treatment, total FARS score improved by an average of 9%. While all subscales improved, bulbar and upper limb coordination subscales were most improved, by 80% and 53%, respectively. Mean improvements persisted at 18 months from baseline, although these findings were attenuated.2

A phase 2 trial (NCT05485987) is currently recruiting to assess the pharmacokinectics and safety of vatiquinone in children with FA younger than 7 years. To be eligible, participant’s can’t be treated with anticoagulants, aspirin, or strong cytochrome P450 3A4 inducers/inhibitors for 30 days before the first visit and while on the study. In the study, participants will receive vatiquinone 3 times daily for 72 weeks, at doses of 15 mg/kg if they weigh less than 13 kg, or 200 mg if they weigh more.3

1. PTC Therapeutics announces topline results from vatiquinone MOVE-FA registration-directed trial. News release. May 23, 2023. Accessed May 25, 2023.
2. Sullivan K, Freeman M, Shaw J, et al. EPI-743 for Friedreichs ataxia patients with point mutations. Neurology. 2016;86(16 supplement).
3. A study of vatiquinone for the treatment of participants with Friedreich ataxia. March 24, 2023. Accessed May 25, 2023.
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