EPI-743 for Freidreich’s Ataxia Point Mutations

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Conference Abstract

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Objective: To assess the effects of EPI-743 in patients with Friedreich’s Ataxia (FA) point mutations on neurologic function as measured by the Friedreich’s Ataxia Rating Scale (FARS).

Background: FA is an autosomal recessive degenerative disorder characterized by ataxia, dysarthria, sensory loss, diabetes, and cardiomyopathy. FA patients with a point mutation (FA-PM) carry an expanded GAA repeat on one allele and a point mutation/deletion on the other allele; this is a rare variant. The natural history of FA includes progressively deteriorating neurologic function with FARS worsening 3.55 points in 12 months and 6.16 points in 24 months. EPI-743 is a therapeutic being developed for treatment of patients with mitochondrial diseases and disorders of oxidative stress.

Methods: Three patients with genetically confirmed FA-PM (G130V) were administered EPI-743 400mg PO TID for 18 months in an open-label study. Assessments were completed quarterly. Relative mean changes in FARS total and subscale scores from baseline to 6 and 18 months of treatment were calculated as change([percnt]) = ((meanX - mean0) / mean0 × 100) where X represents the time point.

Results: After 6 months of treatment, total FARS score improved an average of 9[percnt] (baseline mean total FARS=64, 6m mean total FARS=58). While all subscales improved, bulbar and upper limb coordination sub-scales were most improved (bulbar mean improvement of 80[percnt] [from 0.83 to 0.17] and upper limb coordination 53[percnt] [from 3.17 to 1.5]). Mean improvements persisted at 18 months from baseline (FARS total: 6[percnt], bulbar subscale: 20[percnt], upper limb coordination: 37[percnt]), although they attenuated. No serious adverse events, including hematologic or cardiac, were observed.

Conclusions: EPI-743 was associated with clinically significant improvement in neurological function in patients with FA-PM over 18 months. These findings support further study of EPI-743 in patients with FA due to point mutations.