Vatiquinone found to slow FA progression by 75% after 1.5 years
But oral therapy fails to meet primary goal in Phase 2/3 trial
In key secondary measures, PTC Therapeutics‘ oral therapy candidate for FA also demonstrated significant benefits among patients in upright stability, fatigue, and face and neck (bulbar) symptoms.
However, across the primary analysis population, the trial failed to meet its primary goal of an overall statistically significant change in disease progression.
“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, PTC’s CEO, said in a press release.
“Given the signals of clinical benefit, vatiquinone’s well-established safety profile in children, and the unmet medical need for pediatric patients with FA,” Klein added, “we look forward to discussing a potential path to registration with regulatory authorities.”
Benefits of vatiquinone seen in stability, fatigue measures in trial
Vatiquinone, formerly known as EPI-743, is an orally administered small molecule designed to access the brain and block the activity of 15-lipoxygenase, an enzyme that regulates neuroinflammation processes involved in FA. The treatment had been previously tested in more than 500 patients with up to 10 years of exposure — showing a favorable safety profile.
A small Phase 2 trial (NCT01962363), completed in 2016, tested vatiquinone in three people with FA for six months. Data showed the treatment significantly reduced disease severity, as compared with FA’s natural course in untreated patients matched in age and disease stage, for at least 18 months.
The Phase 2/3 MOVE-FA study (NCT04577352), launched in 2020, enrolled 146 pediatric and adult FA patients, ages 7 and older — with the majority younger than 18. Eligible participants could walk at least 10 feet in one minute, with or without assistance, and swallow capsules.
Participants were randomly assigned to receive vatiquinone or a placebo three times daily for 72 weeks, or about 17 months. Older patients and/or those weighing at least 25 kg (about 55 pounds) received 400 mg capsules, while children younger than 12 and weighing less than 25 kg received 200 mg capsules.
The trial’s main goal was vatiquinone’s impact on the modified Friedreich Ataxia Rating Scale (mFARS) scores, a disease progression measure focusing on swallowing and speech, upper and lower limb coordination, and upright stability. A key secondary measure was a change in activities of daily living as assessed by the FARS Activities of daily living (FARS-ADL) score.
Although 72 weeks of vatiquinone improved the mean mFARS scores by 1.6 points compared with the placebo, the difference was not statistically significant.
Still, there was a significant treatment benefit in subscales of upright stability and bulbar symptoms. According to PTC, these symptoms reflect key aspects of disease severity and predict a faster decline in walking abilities. The treatment also significantly eased fatigue, as recorded by the Modified Fatigue Scale.
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.
The researchers also noted that, in a prespecified analysis of those who completed the full 72 weeks of therapy, the placebo-corrected difference was 2.31 points. That represented a 75% slowing in disease progression.
Overall, vatiquinone was well tolerated, the company said.
All MOVE-FA trial participants who completed the full 72 weeks of treatment have the option to enter an open-label extension phase to receive 24 weeks, or nearly six months, of vatiquinone.