FDA Issues CRL for Vatiquinone in Friedreich Ataxia, Requests More Efficacy Data

Today, the FDA issued a complete response letter (CRL) to the new drug application (NDA) for vatiquinone in children and adults with Friedreich ataxia (FA), a rare, progressive neuromuscular disorder that primarily affects the central nervous system and heart, according to a statement by PTC Therapeutics.¹

Vatiquinone is a first-in-class small molecule that selectively inhibits 15-lipoxygenase (15-LO), an enzyme involved in the energetic and oxidative stress pathways disrupted in patients with FA. By inhibiting 15-LO, the therapy helps alleviate mitochondrial dysfunction, promote neuronal survival, and reduce oxidative stress and inflammation.

In its CRL, the FDA stated that the data submitted in support of the NDA did not demonstrate substantial evidence of efficacy. Because of this, the agency is requiring an additional adequate and well-controlled study before resubmission. If approved, vatiquinone would become the second marketed treatment for FA, following Biogen’s omaveloxolone, approved in 2023 for patients 16 years and older.²

“We are of course disappointed by the FDA’s decision to not approve vatiquinone,” Matthew B. Klein, MD, CEO of PTC Therapeutics, said in a statement.¹ “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 ataxia. We plan to meet with the FDA to discuss potential steps to address the issues raised in the CRL.”

NDA Supporting Data Fall Short

The NDA was primarily supported by results from the phase 3 MOVE-FA trial (NCT04577352).³ It enrolled 146 patients aged 7 and older with FA who were randomized to receive either active vatiquinone treatment or placebo for 72 weeks.⁴ The study did not meet its primary end point of modified Friedreich Ataxia Rating Scale (mFARS) change from baseline; the mean placebo-corrected change was 1.6 (P = .14).

However, vatiquinone showed significant improvement in the bulbar and upright stability subscales, which reflect key drivers of morbidity and predict loss of ambulation.

“While we are disappointed that the study did not achieve its primary end point, we are encouraged by the findings of meaningful impact on several different aspects of FA disease progression and morbidity over 72 weeks,” Klein said in a statement.

Additional evidence supporting the NDA came from 2 long-term trials in pediatric and adult patients with FA.⁵ Both met their primary end points, demonstrating statistically significant slowing of disease progression compared with natural history cohorts. In one trial, treatment with vatiquinone resulted in a 3.7-point benefit in mFARS (P < .001; n = 70) at 144 weeks, representing a 50% slowing of disease progression.

Also, in an open-label study of adults, vatiquinone treatment was associated with a 4.8-point mFARS benefit at 24 weeks compared with natural history populations (P < .0001; n = 41). Across trials, vatiquinone maintained a well-tolerated safety profile, with no serious treatment-related adverse events reported.

“The results of the extension studies provide further evidence of the potential benefit of vatiquinone in slowing disease progression,” Klein said in a news release. “In addition, the strong safety profile of vatiquinone positions it to be a potentially meaningful therapy for all Friedreich ataxia patients, particularly children and adolescents for whom there are no approved therapies.”

References

1. PTC Therapeutics receives complete response letter for vatiquinone NDA. News release. PTC Therapeutics. August 19, 2025. Accessed August 19, 2025. https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-receives-complete-response-letter-vatiquinone
2. Meglio M. FDA denies approval for Friedreich ataxia agent vatiquinone, citing more efficacy needed. NeurologyLive^®. August 19, 2025. Accessed August 19, 2025. https://www.neurologylive.com/view/fda-denies-approval-friedreich-ataxia-agent-vatiquinone-citing-more-efficacy-needed
3. A study to assess the efficacy and safety of vatiquinone for the treatment of participants with Friedreich ataxia (MOVE-FA). ClinicalTrials.gov. Updated March 27, 2024. Accessed August 19, 2025. https://clinicaltrials.gov/study/NCT04577352
4. PTC Therapeutics announces topline results from vatiquinone MOVE-FA registration-directed trial. News release. PTC Therapeutics. May 23, 2023. Accessed August 19, 2025. https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-announces-topline-results-vatiquinone-move-fa
5. PTC Therapeutics announces positive results from long-term treatment studies and updates on regulatory progress for vatiquinone Friedreich ataxia program. News release. PR Newswire. October 8, 2024. Accessed August 19, 2025. https://www.prnewswire.com/news-releases/ptc-therapeutics-announces-positive-results-from-long-term-treatment-studies-and-updates-on-regulatory-progress-for-vatiquinone-friedreich-ataxia-program-302269891.html