PTC Formally Submits NDA for Vatiquinone as Treatment for Adults and Children With Friedreich Ataxia

Author(s):

Key Takeaways

Vatiquinone, a 15-Lipoxygenase inhibitor, is under FDA review for treating Friedreich ataxia in children and adults.
MOVE-FA trial showed significant benefits in the Upright Stability Subscale, despite not meeting the primary endpoint.
Long-term studies demonstrated a 50% slowing of disease progression and no serious adverse events.
Vatiquinone showed a 42% reduction in disease progression per year in treated patients.

Vatiquinone, a small molecule inhibitor, demonstrated its efficacy and safety across a range of age groups with Friedreich ataxia, with effects seen on disease progression and specific subscales of the mFARS.

Matthew B. Klein, MD

According to an announcement from PTC Therapeutics, the company has submitted a new drug application (NDA) to the FDA for its investigational agent vatiquinone as a potential therapy for children and adults with Friedreich ataxia (FA). If approved, it would become the first and only marketed treatment for children living with the disease.¹

The submission for vatiquinone, a first-in-class selective inhibitor of 15-Lipoxygenase (15-LO), was based on data from the placebo-controlled MOVE-FA study (NCT04577352) as well as 2 long-term trials that featured both pediatric and adults with FA. MOVE-FA, a global registrational-directed trial, included 146 pediatric, adolescent, and adult patients with FA, the majority of whom were under 18 years of age. That study, along with the 2 other long-term trials, provided evidence for vatiquinone’s clinically meaningful effect on slowing disease progression in patients with FA.

In MOVE-FA, while the primary end point of change in overall modified Friedreich Ataxia Rating scale (mFARS) did not reach statistical significance (P = 0.14), a statistically significant effect (P = .021) was recorded on the mFARS upright stability subscale, a pre-specified end point. In the extension of MOVE-FA, treatment with vatiquinone resulted in a 3.7-point benefit (P <.0001; n = 70) in mFARS at 144 weeks relative to a matched natural history cohort from the Friedreich Ataxia Clinical Outcome Measures disease registry.^2,3

"We are excited to have reached this important milestone in the development of vatiquinone," Matthew B. Klein, MD, chief executive officer at PTC, said in a statement.¹ "The evidence of short- and long-term efficacy as well as the extensive safety data collected, particularly in children, supports the potential for vatiquinone to fill the significant unmet need for children living with Friedreich ataxia as well as provide a potential treatment option for adults living with FA.”

While it did not meet its primary end point in the original double-blind MOVE-FA study, vatiquinone did result in clinically meaningful and statistically significant 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. Treatment with the agent also resulted in delayed loss of functional measures represented by individual items within the USS, including items E2B (feet apart eyes closed) and E3A (feet together eyes open). Of note, a comparison of the rate of disease progression on USS predicted a 42% reduction in disease progression per year in those treated with vatiquinone.⁴

Both of the 2 long-term open-label extension studies being used in the NDA met their primary end points, demonstrating statistically significant impacts on disease progression. In the MOVE-FA extension, the 3.7-point difference between vatiquinone and the natural history cohort represented a clinically meaningful 50% slowing of disease progression in 3 years. Above all, the therapy was safe and well tolerated, with no treatment-related serious adverse events reported in the extension studies.

In a prior phase 2 trial (NCT01962363) not included in the NDA, vatiquinone showed a statistically significant impact on disease severity in FA, with a small-scale study of 4 individuals demonstrating an average 9% improvement in total FARS scores after 6 months of treatment. While all subscales improved, the bulbar and upper limb coordination subscales saw the greatest improvements, at 80% and 53%, respectively. These mean improvements persisted at 18 months from baseline, though they were attenuated.

REFERENCES
1. PTC Therapeutics Announces Vatiquinone NDA Submission to FDA for the Treatment of Children and Adults Living with Friedreich Ataxia. News release. December 19, 2024. Accessed December 23, 2024. https://www.prnewswire.com/news-releases/ptc-therapeutics-announces-vatiquinone-nda-submission-to-fda-for-the-treatment-of-children-and-adults-living-with-friedreich-ataxia-302336134.html
2. PTC Therapeutics announces topline results from vatiquinone MOVE-FA registration-directed trial. News release. May 23, 2023. Accessed December 23, 2024. https://www.prnewswire.com/news-releases/ptc-therapeutics-announces-topline-results-from-vatiquinone-move-fa-registration-directed-trial-301832658.html
3. PTC Therapeutics Announces Positive Results from Long-Term Treatment Studies and Updates on Regulatory Progress for Vatiquinone Friedreich Ataxia Program. News release. PTC Therapeutics. October 8, 2024. Accessed December 23, 2024. 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
4. Lynch D, Duquette A, França MC, et al. Safety and Efficacy of Vatiquinone Treatment in Friedreich Ataxia Patients from MOVE-FA: a Phase 3, Double-blind, Placebo-controlled Trial. Presented at: 2024 MDA Clinical and Scientific Conference; March 3-6; Poster S79.