Vatiquinone (PTC-743)

Research conducted from 2004-2011 found that Tocotrienols, which are found in Vitamin E, were shown to protect cells, including neurons, in culture. The mechanism of action was thought to be antioxidant activity to reduce oxidative stress. EPI-743, a novel para-benzoquinone or synthetic analog of vitamin E, was then used in open label clinical trials in a number of diseases to test its safety and efficacy in people.  

In 2012, several publications reported on open-label clinical studies of EPI-743 (aka PTC-743) in mitochondrial diseases, such as Leigh syndrome and Leber Hereditary Optic Neuropathy. In both studies, there was evidence that patients receiving EPI-743 had clinical improvements and no adverse events were observed. An earlier publication reports on experience in treating 14 patients with various mitochondrial conditions with EPI-743. This open-label study reports “EPI-743 has modified disease progression in > 90% of patients in this open-label study as assessed by clinical, quality-of-life, and non-invasive brain imaging parameters” and controlled trials to follow-up these findings.

In 2013, Edison Pharmaceuticals launched a Phase 2 clinical trial of vatiquinone (then known as EPI-743) in adults with Friedreich’s ataxia, enrolling participants through the FARA Patient Registry at three U.S. sites.

In 2016, results were reported from an open-label study of EPI-743 in individuals with point mutations. Later that same year, Edison presented results from the Phase 2 trial showing that EPI-743 was safe and well-tolerated over a two-year period. Although it did not meet its primary endpoint (which was a measure of vision) at six months, investigators observed trends toward improvement in neurological function, and later analyses suggested meaningful gains compared to matched natural history data.

Edison Pharmaceuticals rebranded as BioElectron Technology Corporation in 2017, and in 2019, PTC Therapeutics acquired BioElectron’s assets, including EPI-743.

In 2021, PTC Therapeutics initiated the Phase III MOVE-FA study, an 18-month, placebo-controlled trial evaluating vatiquinone in children and young adults with Friedreich’s ataxia. The study enrolled more than 140 participants across 14 sites in 9 countries.

In 2022, PTC initiated an open-label study evaluating the pharmacokinetics, safety, and efficacy of vatiquinone in children with FA younger than 7 years of age.

In 2023, PTC reported topline results from MOVE-FA. The study did not meet its primary endpoint of a statistically significant change in mFARS at 72 weeks in the overall study population. However, vatiquinone demonstrated statistically significant benefit on measures of fatigue and upright stability. In a pre-specified analysis of participants who completed the full 72-week study (n=96), statistically significant benefits were observed across mFARS, upright stability, and fatigue measures. In this analysis, the placebo-corrected difference in mFARS was 2.31 points, representing a 75% slowing in disease progression over 72 weeks.

In 2024, PTC reported that the pre-specified endpoint was met in two long-term extension studies, demonstrating durable treatment effects on disease progression.

In December 2024, PTC Therapeutics submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for vatiquinone as a treatment for Friedreich’s ataxia. The application was based on data from the placebo-controlled MOVE-FA study and two long-term extension studies.

In August 2025, FDA issued a Complete Response Letter (CRL), stating that substantial evidence of efficacy had not been demonstrated and that an additional adequate and well-controlled study would be needed to support NDA resubmission. PTC indicated that it would continue ongoing vatiquinone studies and provide treatment to participants already enrolled in those studies.

In February 2026, PTC reported that, following a Type C meeting with FDA, an additional study would be needed to support a future NDA resubmission and that an open-label study using a natural history control group could be an acceptable approach. PTC subsequently announced plans for the Phase III PROVE-FA study.

In 2026, PTC Therapeutics announced plans for a Phase III study called PROVE-FA to support a future NDA resubmission for vatiquinone.

PROVE-FA will be an open-label study in which all participants will receive vatiquinone. The study is expected to enroll approximately 120 ambulatory children and young adults with FA and will evaluate change in mFARS over 24 months using a natural history comparison.

Enrollment is planned to begin in Q3 ’26.