PTC to Submit NDA for Vatiquinone in Friedreich Ataxia Following Positive Long-Term Extension Data

Matthew B. Klein, MD, chief executive officer at PTC

Vatiquinone, an investigational agent in development for Friedreich ataxia (FA), met its prespecified primary end point in 2 different long-term open-label extension studies, with highly statistically significant impacts shown on disease progression. PTC Therapeutics, the drug manufacturers of the therapy, have already met with the FDA and plan to submit a new drug application (NDA) for potential approval in December 2024.¹

According to the company, the NDA will include results from the placebo-controlled portion of the phase 3 MOVE-FA study (NCT04577352), as well as confirmatory evidence from the 2 new long-term treatment analyses. Furthermore, it will also comprise mechanistic data showcasing the treatment effect of vatiquinone, a small molecule, first-in-class selective inhibitor of 15-Lipoxygenase, on biomarkers of disease pathology.

MOVE-FA was a global registration-directed trial of vatiquinone that included 146 pediatric, adolescent, and adult patients with FA, the majority of whom were under 18 years of age. In the newly announced long-term data, results showed that after 144 weeks of treatment with the therapy, patients showed a 3.7-point benefit (P <.0001; n = 70) on modified Friedreich Ataxia Rating Scale (mFARS), the primary end point, relative to a matched natural history cohort from the Friedreich Ataxia Clinical Outcome Measures disease registry.

"The results of the extension studies provide further evidence of the potential benefit of vatiquinone in slowing disease progression," Matthew B. Klein, MD, chief executive officer at PTC, said in a statement.¹ "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. We look forward to submitting the NDA by the end of the year."

The 3.7-point different between vatiquinone and the natural history cohort represented a clinically meaningful 50% slowing of disease progression in 3 years. Above all, the therapy was considered safe and well tolerated, with no treatment-related serious adverse events reported in the extension studies. Vatiquinone was even more effective in an additional open-label study earlier study of adults with FA. After 24 months of treatment with the therapy, participants showed a 4.8-point benefit on the mFARS relative to a matched natural history population (P <.0001; n = 41).

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These newly announced long-term data further confirmed the treatment benefit of vatiquinone, which was originally demonstrated in the double-blind portion of MOVE-FA. In MOVE-FA, vatiquinone did not meet its primary end point; however, the therapy did show positive benefit on other key disease subscales and secondary end points. After the 72-week treatment period, investigators documented a mean placebo-corrected change in mFARS score of 1.6 (P = .14). Despite this, patients on the agent showed significant benefits in the bulbar and upright stability subscales (P = .044 and P = .021).2

"MOVE-FA was a well-conducted international clinical trial in children and adults with Friedreich's ataxia. Both this trial data and the open-label extension data are compelling with positive results in clinical endpoints that are meaningful to the FA community," Jennifer Farmer, chief executive officer at the Friedreich’s Ataxia Research Alliance, said in a statement.¹ "We are also encouraged that vatiquinone treatment continues to be safe and well-tolerated. Given the high unmet need, especially in the pediatric population, we are excited that PTC Therapeutics is submitting an NDA."

Most recently, an analysis of MOVE-FA presented at the 2024 International Congress of Parkinson’s Disease and Movement Disorders, showed that vatiquinone resulted in clinically meaningful and statistically significant treatment effects on the Upright Stability Subscale (USS), a sensitive and predictive end point for risk of loss of ambulation. After 72 weeks of treatment, significant benefits were recorded in USS (–1.26; P = .021) in the modified intent-to-treat population. Vatiquinone treatment also delayed the loss of functional milestones represented by individual items within the USS, specifically items E2B (feet apart eyes closed) and E3A (feet together eyes open).

REFERENCES
1. PTC Therapeutics Announces Positive Results from Long-Term Treatment Studies and Updates on Regulatory Progress for Vatiquinone Friedreich Ataxia Program. News release. PTC Therapeutics. 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
2. PTC Therapeutics announces topline results from vatiquinone MOVE-FA registration-directed trial. News release. May 23, 2023. Accessed October 8, 2024. https://www.prnewswire.com/news-releases/ptc-therapeutics-announces-topline-results-from-vatiquinone-move-fa-registration-directed-trial-301832658.html
3. Lynch D, Duquette A, Franca M, et al. Improvement in Upright Stability subscale of mFARS with Vatiquinone Treatment in MOVE-FA: a Phase 3, Double-blind, Placebo-controlled Trial. Presented at: 2024 MDS Congress; September 27-October 1; Philadelphia, PA. ABSTRACT 638.