Last updated Nov. 30, 2022, by Teresa Carvalho, MS
 Fact-checked by José Lopes, PhD
What is vatiquinone for Friedreich’s ataxia?
Vatiquinone (PTC-743), previously known as EPI-743, is an oral small molecule designed to limit neuroinflammation and nerve cell damage in people with Friedreich’s ataxia (FA).
The U.S. Food and Drug Administration (FDA) granted orphan drug and fast track designations to vatiquinone for treating FA. Both designations are meant to accelerate clinical development.
The therapy candidate is being developed by PTC Therapeutics after the company acquired asssets from BioElectronTechnology Coporation.
How does vatiquinone work?
FA is caused by mutations in the gene that contains information to produce the protein frataxin, which is required for mitochondria, the energy factories of the cells, to function normally.
Decreased levels of frataxin, as observed in people with FA, disrupt the normal function of mitochondria, leading to oxidative stress and chronic inflammation. Oxidative stress results from an imbalance between the production of so-called free radicals and the body’s ability to eliminate them, which can lead to cellular damage.
Vatiquinone works by blocking the activity of 15-lipoxygenase, an enzyme that regulates signaling pathways that control neuroinflammation and oxidative stress.
The investigational therapy has the potential to exert its effects in the central nervous system, comprised of the brain and spinal cord, as it can cross the blood-brain barrier (BBB), a highly selective membrane that regulates what substances from the bloodstream can access the brain.
How will vatiquinone be administered in FA?
Vatiquinone is an oral therapy that’s been given in clinical trials as a solution or capsules at doses of 200 mg or 400 mg, administered three times daily.
Vatiquinone in clinical trials
Vatiquinone has shown a favorable safety profile in more than 500 patients treated for 10 years. The effectiveness of the therapy has been assessed in several Phase 2 trials in FA.
Phase 2 trials
A placebo-controlled Phase 2 study (NCT01728064) examined the safety and effectiveness of vatiquinone on visual and neurological function in FA patients. A total of 63 participants were randomly assigned to receive 200 or 400 mg of vatiquinone, given in capsules, or a placebo, three times daily. After six months of treatment, the placebo group started on 200 or 400 mg of vatiquinone, whereas the remaining patients continued vatiquinone at the same dose for an additional six months.
Clinical assessments included the Friedreich’s ataxia rating scale to evaluate neurological function (FARS-Neuro), visual acuity assessments, and the 25-foot walk test of neuromuscular function, among others.
Results indicated no significant differences in visual function, neurological function or cardiac function at six months between participants treated with vatiquinone and those who received a placebo. However, in a subsequent analysis, the researchers found that more patients taking vatiquinone had an improvement of at least three points in the FARS-Neuro scale.
Vatiquinone treatment was found to be safe and well tolerated, with no serious treatment-related side effects or toxicity.
A small Phase 2 study (NCT01962363)Â evaluated vatiquinone in four patients with rare point mutations leading to FA. Results demonstrated a statistically significant benefit on disease severity at two years of treatment, as assessed by the modified FARS (mFARS) scale.
Ongoing trials
The Phase 2/3 MOVE-FA study (NCT04577352) is testing the safety and effectiveness of vatiquinone in people with FA, ages 7 and older.
MOVE-FA — ongoing in the U.S., Canada, Australia, New Zealand, Brazil, Germany, Spain, France, and Italy — has recruited 146 FA patients who can walk at least 10 feet (about three meters) in one minute with or without assistance, and can swallow capsules.
Participants are randomly assigned to receive either vatiquinone or a placebo three times a day for 72 weeks (about 16.5 months). Children younger than 12 and weighing less than 25 kg (about 55 pounds) receive the therapy in 200 mg capsules. Older patients and/or those weighing at least 25 kg receive 400 mg capsules.
The trial’s main outcome measure is the change in mFARS at week 72. Other measures include changes in the ability to perform daily activities, functional status, walking endurance, and number of falls. An open-label extension phase lasting 24 weeks (about six months) will follow with participants taking vatiquinone at the dose they received in the previous phase.
A Phase 2 trial (NCT05485987), Study PTC743-NEU-005-FA is recruiting patients to assess the pharmacokinetics (the movement into, through, and out of the body) and safety of vatiquinone in children with FA younger than 7. It expects to recruit five children at Children’s Hospital of Philadelphia.
To be eligible, participants can’t be being treated with anticoagulants, aspirin, or strong cytochrome P450 (CYP) 3A4 inducers/inhibitors (such as ketoconazole, rifampin, and St. John’s wort) for 30 days before the first visit and while on the study, and must be able to take the oral vatiquinone solution with food.
Participants will receive vatiquinone three times daily for 72 weeks, at 15 mg/kg if they weigh less than 13 kg (28.66 pounds), or 200 mg if they weigh more.
Participants in MOVE-FA or Study PTC743-NEU-005-FA trial may also join an international, long-term, open-label extension study (NCT05515536) of vatiquinone. In this Phase 3 trial, patients will continue on the same dose unless they meet age or weight criteria for change. The primary outcome measure will be the number of participants with side effects, assessed up to five years of treatment, whereas the secondary measure will be a change in mFARS at year five.
Common side effects of vatiquinone
The most frequent side effects found in clinical trials with FA patients, include:
- impaired taste (dysgeusia)
- increased weight
- indigestion
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