If approved, vatiquinone would have been the first therapy approved for pediatric patients with FA.
FDA issues CRL for vatiquinone to treat Friedreich's ataxia | Image credit: Contemporary Pediatrics
Citing that substantial evidence of efficacy was not demonstrated, the FDA has issued a complete response letter (CRL) for PTC Therapeutics' Friedreich's ataxia (FA) candidate vatiquinone. The CRL was issued on the therapy's target action date of August 19, 2025. If it had been approved, vatiquinone—a small molecule, first-in-class selective inhibitor of 15-Lipoxygenase (15-LO)—would have become the second therapy approved for patients with FA, behind Biogen's omaveloxolone (approved for ages 16 years and older).1-3
The new drug application for vatiquinone was based on findings from the placebo-controlled MOVE-FA study, along with data from 2 long-term studies involving both pediatric and adult FA patients.2
The MOVE-FA trial, a global phase 3 study (NCT04577352), enrolled 143 FA patients aged 7 years and older, with a modified FA Rating Scale (mFARS) score between 20 and 70, and the ability to ambulate at least 10 feet in one minute with or without assistance. The primary endpoint measured the placebo-corrected change from baseline in mFARS at 72 weeks. The intent-to-treat (ITT) population had a mean age of 18.7 years, while the modified ITT (mITT) population, consisting of 123 subjects aged 7-21 years, had a mean age of 14.6.
Results from the mITT population showed a -1.61 (P = 0.144) change in mFARS at 72 weeks relative to placebo. A consistent vatiquinone treatment benefit was observed across primary, secondary, and exploratory endpoints. Notably, nominally significant benefits were recorded in the Upright Stability subscale (USS) of mFARS (-1.26 [P = 0.021]), a key metric for disease progression in younger, ambulatory FA patients, and the Modified Fatigue Impact Scale (MFIS), -5.05 (P = 0.025). Vatiquinone was well tolerated, with no difference in treatment-related adverse events between treatment and placebo groups.
"We are of course disappointed by the FDA's decision to not approve vatiquinone," said Matthew B. Klein, MD, chief executive officer of PTC Therapeutics, in a press release. "We believe the data collected to date demonstrate that vatiquinone could provide a safe and effective therapy for both children and adults living with Friedreich's ataxia. We plan to meet with the FDA to discuss potential steps to address the issues raised in the CRL."1
According to PTC, FA is a rare, physically debilitating, life-shortening, neuromuscular disorder that mainly affects the central nervous system and the heart, and is the most common hereditary ataxia. The disorder is usually caused by a single genetic defect in the frataxin (FXN) gene that leads to reduced production of frataxin, a mitochondrial protein that is important for cellular metabolism and energy production. Globally, FA impacts approximately 25,000 people.
On June 18, Biogen announced the dosing of participants in the BRAVE study (NCT06953583), a global phase 3 clinical trial evaluating omaveloxolone (Skyclarys) in children aged 2 to younger than 16 years with Friedreich ataxia (FA).4
In approximately 255 children living with FA, the BRAVE trial will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of once-daily oral omaveloxolone. Participants will be randomized 2:1 to receive either once-daily omaveloxolone or placebo for 52 weeks before entering an open-label extension period lasting up to week 104. The primary efficacy outcome will measure change in Upright Stability Score (USS), a validated subscale of the modified Friedreich’s Ataxia Rating Scale (mFARS).
Click here for more information on omaveloxolone.
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