PTC Therapeutics has announced positive long-term data for vatiquinone in treating Friedreich's ataxia (FRDA), a rare and debilitating neurodegenerative disease. The data, stemming from the MOVE-FA long-term extension study, indicate a significant reduction in disease progression as measured by the modified Friedreich Ataxia Rating Scale (mFARS). This development marks a potential advancement in the treatment landscape for FRDA, where limited options currently exist.
Long-Term Efficacy of Vatiquinone
The MOVE-FA study, an 18-month, placebo-controlled Phase 3 trial, evaluated vatiquinone in children and young adults with FRDA. While the initial 72-week results, reported in May 2023, did not meet the primary endpoint of a statistically significant change in mFARS score, clinically meaningful benefits were observed in key secondary endpoints. The subsequent long-term extension study, evaluating 144 weeks of vatiquinone treatment, demonstrated a 3.7-point benefit on mFARS compared to a matched natural history cohort from the Friedreich Ataxia Clinical Outcome Measures (FACOMS) disease registry. According to the company, this benefit can be interpreted as a clinically meaningful 50% slowing of disease progression over three years compared to the natural course of the disease.
Mechanism of Action
Vatiquinone is a first-in-class selective inhibitor of 15-Lipoxygenase (15-LO). This enzyme plays a crucial role in regulating energetic and oxidative stress pathways, which are implicated in the pathophysiology of Friedreich's ataxia. By inhibiting 15-LO, vatiquinone helps mitigate the effects of mitochondrial dysfunction and oxidative stress, thereby promoting neuronal survival.
Regulatory Pathway
PTC Therapeutics plans to submit a New Drug Application (NDA) to the FDA for vatiquinone's approval by December 2024. The NDA will include data from the placebo-controlled portion of the MOVE-FA study, along with confirmatory evidence from the two long-term treatment analyses and mechanistic data demonstrating the treatment's effect on biomarkers of disease pathology.
Clinical Significance
Friedreich's ataxia is a rare, inherited disease that causes progressive damage to the nervous system, resulting in symptoms such as muscle weakness, loss of coordination, and heart problems. Currently, treatment options are limited, and there is a significant unmet need for therapies that can slow or halt disease progression. If approved, vatiquinone could provide an additional treatment option for patients with FRDA, potentially improving their quality of life and opening avenues for further research into similar therapies. The promising results from the MOVE-FA study, supported by analyses of disease biomarkers, suggest that PTC has addressed previous concerns related to the drug's efficacy. The potential FDA approval would represent a significant step forward in addressing this rare condition and improving outcomes for affected individuals.
