Vatiquinone (PTC-743)

2004-2011: 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.  

2012: Several publications report 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.

The first regulatory filing for EPI-743 was for a 13-week emergency treatment protocol in people with mitochondria disease, followed by an extension protocol, for individuals who were considered to be at risk of progressing to end-of-life care within 90 days. The study was run at Stanford University, Medical University of South Carolina, University of California, Los Angeles, CHOC Children’s Hospital, and Akron Children’s Hospital.

January 2013: Edison Pharmaceuticals announced the launch of a Phase 2 clinical trial of EPI-743 in adults with FA. There were three sites – University of South Florida, Children’s Hospital of Philadelphia and University of California Los Angeles. Subjects were recruited through the FARA Patient Registry, and all subjects were enrolled by the fall of 2013.

March 2014: Edison announced that FDA granted EPI-743 Fast Track designation.

April 2016: Results were reported from the open-label study of EPI-743 in FA patients with point mutations and can be accessed here.

September 2016: Study investigators reported the results of the EPI-743 phase 2 trial at the FA educational symposium. A total of 63 subjects were enrolled in the trial. EPI-743 was found to be safe and well-tolerated over the entire 24 months study period. There were no significant differences between EPI-743 treatment groups and placebo at 6 months on the primary endpoint, a measure of vision; however, there was a trend towards improvement in neurological function as assessed by the FARS neuro scale. In the analysis of the entire 24-month trial there was suggested evidence of a significant improvement in neurological function based on the FARS score in EPI-743 treated subjects when compared to an age, sex and disease-severity matched natural history cohort followed as part of the Friedreich’s Ataxia-Clinical Outcomes Measures Study (FA-COMS). Results of this clinical trial have been published and can be accessed here.

Early 2017: Edison Pharmaceuticals announced name change to BioElectron Technology Corporation.

Late 2019: PTC Therapeutics acquired assets from BioElectron Technology Corporation which included EPI-743.

2022: PTC started a Phase II EPI-743 Clinical trial – An Open-Label Study to Evaluate Pharmacokinetics, Safety, and Efficacy of Vatiquinone in Children With Friedreich Ataxia Younger Than 7 Years of Age

January 2021: PTC initiates a registration-directed Phase III trial, MOVE-FA study, evaluating vatiquinone in children and young adults with Friedreich ataxia (FA). The Phase 3 MOVE-FA trial is an 18-month parallel arm, placebo-controlled study evaluating vatiquinone versus placebo in children and young adults with FA. The primary endpoint is the change from baseline in mFARS, with key secondary endpoints assessing ambulation and activities of daily living.

November 2021: The study completed enrollment with >140 subjects enrolled across 14 sites in 9 different countries.

PTC Therapeutics would like to express their gratitude to the Friedreich ataxia community, patients, and families. We appreciate the commitment and dedication of those who are participating in, or considered participating in, the MOVE-FA study. PTC remains focused on those who are impacted by this condition and values the partnership of the community.

May 23, 2023: PTC reported topline results from the MOVE-FA trial of vatiquinone in patients with FA. The study did not meet its primary endpoint of statistically significant change in mFARS score at 72 weeks in the primary analysis population (all patients enrolled, ages 7-21yrs, N=123). However, vatiquinone treatment did demonstrate significant benefit on key secondary endpoints that are clinically significant to individuals with FA.  There was significant improvement in the patient reported outcome measure of fatigue, the Modified Fatigue Scale (nominal p value of 0.025). The vatiquinone treated group demonstrated less decline in the upright stability of mFARS (measures standing and walking) compared to the placebo group (p<0.021). The study experienced a higher number of early withdrawals, mostly due to COVID-related issues, so there was an additional prespecified analysis with the population of subjects who completed all visits through week 72 (n=96).  In the population of subjects that completed the study protocol, significance was reached in the mFARS endpoint (p <0.05), upright stability subscale of mFARS (p<0.026), and modified fatigue rating scale (p<0.042). The placebo corrected difference in mFARS was 2.31, which represents a 75% slowing in disease progression over 72 weeks. PTC stated that they will discuss the potential path to registration with FDA and EMA based on these results, the unmet need in children with FA and the favorable safety data for vatiquinone.

January 8, 2024: PTC Therapeutics provided an update on commercial progress and R&D pipeline at the 42nd Annual J.P. Morgan Healthcare Conference. They announced a FDA meeting for vatiquinone to discuss how the MOVE-FA data along with additional clinical and preclinical data could support an NDA submission in FA is scheduled for the first quarter. Additionally, scientific advice feedback from the EMA on a potential submission of vatiquinone for conditional marketing authorization for Friedreich ataxia is expected in the first quarter.

April 25, 2024: In their corporate update and report on first quarter 2024 financial results, PTC announced plans to submit an NDA for vatiquinone for the treatment of FA in late 2024 based on FDA feedback.

October 8, 2024: PTC provided updates on the vatiquinone Friedreich ataxia (FA) program. The pre-specified endpoint for two different FA long-term extension studies was met, with highly statistically significant evidence of durable treatment benefit on disease progression. In addition, PTC recently aligned with FDA on key aspects of the planned NDA submission for vatiquinone in December, 2024. 

December 19, 2024: 

PTC announced the filing of a New Drug Application (NDA) submission for vatiquinone for the treatment of children and adults living with Friedreich Ataxia. The vatiquinone NDA filed with the FDA is based on data from the placebo-controlled MOVE-FA study as well as results from two long-term studies including pediatric and adult FA patients. MOVE-FA was a global registration-directed trial of vatiquinone that enrolled 146 pediatric, adolescent and adult FA patients, the majority of whom were under 18 years of age.

While the primary endpoint of change from baseline in the overall mFARS score did not reach statistical significance (p=0.14), a statistically significant effect (p=0.021) was recorded on the mFARS upright stability subscale, which was a pre-specified endpoint, and the portion of the mFARS now understood to be the most sensitive and relevant for the enrolled primary analysis population. In addition, the effect on upright stability was concordant with favorable treatment effect on the 1-minute walk distance test and the functional component of the Modified Fatigue Rating Scale. The study included a 72-week placebo-controlled phase and a long-term open-label extension. Following completion of MOVE-FA, subjects were eligible to enroll in a long-term, open-label extension study which is ongoing.

The FDA has 60 days to accept or reject the NDA submission. If the submission for vatiquinone is accepted, the FDA then has six months to review the full data package based on the MOVE-FA study before the drug can be approved for treatment of people with FA.

February 19, 2025: 

PTC announced that the U.S. Food and Drug Administration (FDA) has accepted for filing the New Drug Application (NDA) for vatiquinone for the treatment of children and adults living with Friedreich’s ataxia (FA). The application has been granted Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) target action date of Aug. 19, 2025.

The vatiquinone NDA is based on data from the placebo-controlled MOVE-FA study as well as results from two long-term studies including pediatric and adult FA patients. The company stated that data from these three studies demonstrate significant, durable and clinically meaningful evidence of slowing disease progression on key aspects of disease. In addition, these studies demonstrate that vatiquinone is safe and well tolerated in all age groups studied.