Vatiquinone for Friedreich’s ataxia
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What is vatiquinone for Friedreich’s ataxia?
Vatiquinone (PTC-743), previously known as EPI-743, is an investigational oral treatment designed to limit neuroinflammation and nerve cell damage in people Friedreich’s ataxia (FA).
The therapy has received orphan drug and fast track designations by the U.S. Food and Drug Administration for treating FA. It also has orphan drug status in the European Union for the condition. The designations are meant to accelerate clinical development.
It’s under development by PTC Therapeutics, after being acquired in 2019 from BioElectronTechnology Corporation. It’s being investigated for treating seizures in people with mitochondrial diseases.
Therapy Snapshot
| Treatment Name: | Vatiquinone |
| Administration: | Being tested in FA in an oral solution or capsule formulation |
| Clinical testing: | In a Phase 2/3 trial for FA |
How does vatiquinone work in FA?
FA is caused by mutations in the gene that contains information to produce frataxin, a protein needed for the normal function of mitochondria, cells’ energy factories.
Decreased frataxin, as observed with FA, disrupts the 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, a vitamin D derivative, is a small molecule that blocks the activity of 15-lipoxygenase, an enzyme that regulates signaling pathways that control neuroinflammation and oxidative stress. Specifically, 15-lipoxygenase helps convert healthy fats into oxidated fatty acids in response to oxidative stress, which further contributes to oxidative stress and inflammation.
By inhibiting this enzyme, vatiquinone should counteract the mitochondrial abnormalities and oxidative stress seen with FA.
How will vatiquinone be administered in FA?
Vatiquinone is available as oral capsules or as a liquid solution, both taken by mouth. In FA clinical trials, it was tested 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 and other trials are still ongoing.
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 adults were randomly assigned to receive 200 or 400 mg of vatiquinone capsules, or a placebo, three times daily for six months.
After completing the trial, the participants entered an 18-month open-label extension part where all received either the 200 mg or 400 mg dose of vatiquinine for six months. Then they were given 400 mg for one more year.
Clinical assessments included the Friedreich’s ataxia rating scale to evaluate neurological function (FARS-Neuro), visual acuity assessments, and the 25-foot walk test for neuromuscular function.
Results showed no significant differences in visual function, neurological function, or cardiac function at six months between those treated with vatiquinone and those given a placebo. This meant the trial failed to meet its primary and key secondary goals.
In a subsequent analysis, however, the researchers found that more patients taking vatiquinone than a placebo had an improvement of at least three points (66% vs. 43%) and of at least five points (54% vs. 33%) in the FARS-Neuro scale.
The researchers compared patients on this Phase 2 trial with a historical patient group given no treatment. The historical group saw an average reduction in FARS-Neuro of 4.8 points over two years, which is consistent with the natural progression of the disease. Those given vatiquinone for two years had a mean improvement of 1.8 points, indicating a significant slowing in disease progression.
Vatiquinone was safe and well tolerated, with no serious treatment-related side effects or toxicity.
A small Phase 2 study (NCT01962363) evaluated vatiquinone in three patients with rare point mutations leading to FA. The results demonstrated an improvement in FARS scale scores at six months of treatment that persisted at 18 months. The most notable benefits were in face and neck (bulbar) symptoms and upper limb coordination. No serious side effects were observed.
Ongoing trials
MOVE-FA
An ongoing Phase 2/3 clinical trial called MOVE-FA (NCT04577352) is testing vatiquinone in people with FA, ages 7 and older, who can walk at least 10 feet (about three meters) in one minute with or without assistance, and can swallow capsules.
The trial recruited 146 FA patients, most of whom were children and adolescents, who were randomly assigned to receive either vatiquinone or a placebo three times a day for 72 weeks (about 1.4 years). Children younger than 12 and weighing less than 25 kg (about 55 pounds) are receiving the therapy in 200 mg capsules. Older patients and/or those who weigh at least 25 kg are taking 400 mg capsules.
The trial’s main goal is to measure 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.
Vatiquinone slowed FA disease progression by 75% compared with a placebo in patients who completed the full 72 weeks of treatment, top-line results showed. Significant benefits were also seen in upright stability, fatigue, and bulbar symptoms. Despite these benefits, the trial failed to meet its primary goal of a statistically significant change in disease progression across the primary analysis population.
An open-label extension phase lasting 24 weeks (about six months) will follow the placebo-controlled part, wherein all will receive vatiquinone at the age- and weight-adjusted doses used in the previous phase.
PTC743-NEU-005-FA
Another Phase 2 trial called Study PTC743-NEU-005-FA (NCT05485987) is ongoing to assess the pharmacokinetics (the movement into, through, and out of the body) and safety of vatiquinone in five children with FA younger than 7.
Participants are receiving vatiquinone, at 15 mg/kg if they weigh less than 13 kg (28.66 pounds) or 200 mg if they weigh more, three times daily for 72 weeks.
Long-term extension
Participants in the ongoing MOVE-FA or Study PTC743-NEU-005-FA trial may join an international, long-term, open-label study (NCT05515536) of vatiquinone. In this Phase 3 trial, patients will continue on the same dose unless they meet age or weight criteria for a change.
The primary outcome measure will be the number of participants with side effects, assessed up to five years of treatment. The secondary measure will be a change in mFARS at year five.
Common side effects of vatiquinone in FA
The most common side effects of vatiquinone reported in FA clinical trials include:
- impaired taste (dysgeusia)
- increased weight
- indigestion.
Friedreich’s Ataxia News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about Vatiquinone
Vatiquinone is being investigated in the extension part of a Phase 2/3 trial in people with Friedreich’s ataxia as well as a Phase 2 study in children with the disease. While it’s shown promise in earlier trials, more data is needed to establish vatiquinone’s safety and efficacy. Therefore, it’s too early to know if or when the therapy might be approved by the U.S. Food and Drug Administration.
Vatiquinone is an experimental therapy that’s not yet approved for treating Friedreich’s ataxia (FA). It’s designed to limit neuroinflammation and nerve cell damage in people with FA by blocking the activity of an enzyme called 15-lipoxygenase. In clinical trials, this has led to significant reductions in disease progression.
Because vatiquinone is still in the early stages of development, studies examining its interaction with alcohol are lacking. Patients who wish to drink alcohol while taking the medication should discuss this issue with their doctors.
In clinical trials, significant benefits of vatiquinone, such as reduced face and neck (bulbar) symptoms, better upper limb coordination, and improved neurological function, were seen after six months. Because Friedreich’s ataxia has a variable disease course, some patients may see benefits earlier than others. More data is needed to have an idea about how soon patients may see benefits with treatment.
The most common side effects of vatiquinone reported in Friedreich’s ataxia clinical trials involved the gastrointestinal tract and included impaired taste, increased weight, and indigestion. It’s recommended that patients speak with their healthcare providers to understand how the medication may affect them. They should also report any unanticipated side effects of vatiquinone to their doctors.
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