OBJECTIVES: Friedreich Ataxia (FA) is a rare inherited autosomal recessive disease that causes progressive neurodegenerative changes and disability due to impaired muscle coordination. A systematic literature review (SLR) was conducted to assess the published efficacy and safety of therapeutic interventions in FA.

METHODS: Databases of MEDLINE, Embase, and Cochrane were screened via dual review to identify studies that evaluated interventions in clinically confirmed patients with FA. Additionally, trial registries and conference proceedings were hand searched.

RESULTS: In total, 32 relevant publications were identified, of which 24 were randomized controlled trials. These publications investigated idebenone (n=11), recombinant erythropoietin (n=6), omaveloxolone (n=3), amantadine hydrochloride (n=2), and A0001, CoQ10, creatine, deferiprone, interferon-γ-1b, L-cartinine levorotatory form of 5-hydroxytryptophan, luvadaxistat, resveratrol, RT001, vatiquinone (all n=1). Age of study participants ranged from 8 to 73 years and disease duration ranged from 4 to 19 years. The mean GAA1 and GAA2 allele repeat length correlating with disease severity of FA, ranged from 350-930 and 690-864 nucleotides, respectively.

The International Cooperative Ataxia Rating Scale (ICARS, n=10) and Friedreich Ataxia Rating Scale (modified FARS and FARS-neuro, n=10) scores were the most frequently reported efficacy outcomes and determine the degree of disability of FA. The mean change from baseline ranged from -2.9-7 units and -6.1-6.2 units, respectively. Idebenone (n=2), omaveloxolone (n=2), A0001 (n=1) and vatiquinone (n=1) showed improved scores. In many studies, FA deteriorated regardless of treatment. Most frequently reported adverse events (AE) were nausea (n=9), diarrhea (n=7) and headache (n=7). Serious AEs observed were atrial fibrillation (n=1), craniocerebral injury (n=1) and ventricular tachycardia (n=1).

CONCLUSIONS: This SLR highlighted a considerable unmet need for treatments that improve symptoms related to ataxia and neurological symptoms in FA. Currently, novel efficacious drugs are being investigated that aim to improve these symptoms or slow down the progression of the disease.