Objective:

Evaluate the real-world use of Omaveloxolone in Friedreich Ataxia (FA).

Background:

FA, is an autosomal recessive neurodegenerative disorder, showing a suppressed Nrf2 pathway, increase oxidative stress, mitochondrial dysfunction and damage to cells. Omaveloxolone (150 mg per day) significantly improved neurological function compared to placebo when evaluated in a phase II trial in FA patients.

Design/Methods:

Patients starting Omaveloxolone underwent baseline and follow-up visits after 3 and 6 months. Neurological assessments included the modified FA rating scale (mFARS), and FA activities of daily living (FA-ADL) scores. Laboratory analyses included liver enzymes and lipid profile. Variables were assessed with a linear mixed model for repeated measures. Patients were divided based on their median baseline mFARS score (£63.5 or >63.5), and baseline FA-ADL score (£17 or >17).

Results:

We enrolled 60 patients (31 female), with a mean age of 41.3±13.6 and a disease duration of 22.1±10.6 years. Mean±SD baseline mFARS was 58.8±18.1 and decreased to 58.5±16.9 after 3 months and 56.7±15.2 after 6 months (p=0.111). Patients with higher baseline mFARS score were more prone to improvement during the 6-month follow-up (mean difference 2.68, p=0.046). The mean FA-ADL did not show any change (p=.645) during follow-up from baseline (15.2±7.5) to month 3 (15.2±7.5) and month 6 (15.5±6.9). Patients with higher baseline FA-ADL showed a small improvement during follow-up (mean difference 1.309, p=.043). AST and ALT increased during follow-up, with a peak at the 3-month time-point and then decreased (p<0.001 for both). Eleven patients underwent temporary discontinuation for liver enzyme increase, pyrosis, stomatitis, patient’s decision, followed by a re-start with slow titration. Two patients discontinued Omaveloxolone permanently because of gastrointestinal side effects.

Conclusions:

Omaveloxolone was safe and well tolerated. mFARS and FA-ADL showed a higher improvement in patients with a more advanced disease and higher baseline scores at both scales.