OBJECTIVES: Friedreich ataxia is a rare, inherited neurodegenerative disease, leading to progressive ataxia, dysarthria, and sensory loss. In the MOXIe Part 2 (MOXIe2) study and open label extension (NCT02255435; EudraCT2015-002762-23), omaveloxolone slowed disease progression as demonstrated by significant improvement on the modified Friedreich Ataxia Rating Scale (mFARS) compared to placebo and through a propensity matched analysis with patients from the Friedreich’s Ataxia Clinical Outcomes Measures Study (FACOMS). We developed a regression-based model to estimate the change in mFARS over a patient’s lifetime and analyzed MOXIe2 to characterize the functional burden patients face at different mFARS ranges.

METHODS: A regression model was developed to predict the mFARS trajectory of patients using clinical covariates from FACOMS. Omaveloxolone treatment effect was estimated from the propensity matched analysis. Functional burden was characterized at the first visit of each patient in MOXIe2 when mFARS in the relevant range was recorded.

RESULTS: On average, patients receiving omaveloxolone are predicted to take approximately 40% longer to reach a mFARS score of 50 than those who are untreated (11.3 vs 8.1 years). In MOXIe2, severe gait challenges, meaning the need to use a walker or the help of an examiner to walk 8 meters, were observed in 75% (21/28) of patients with a mFARS score of 50-59 vs. 36% (17/47) of patients with a score of 40-49. Similarly, the model predicted that it would take approximately 43% longer for patients on omaveloxolone treatment to reach a mFARS score of 60 than those who were untreated (21.7 vs 15.2 years). In MOXIe2, normal speech patterns were observed in 17% (1/6) of patients with a mFARS score of 60-69 vs. 54% (15/28) of patients with a score of 50-59.

CONCLUSIONS: FA is a progressive disease, and our analyses demonstrate that omaveloxolone provides long term, meaningful preservation of function.