Objective: To assess the long-term effect of vatiquinone (EPI-743) on disease progression in adults with Friedreich’s ataxia (FA) from Study 006, compared with a matched natural history cohort from FACOMS (Friedreich’s Ataxia Clinical Outcome Measures Study).

Background: FA is characterized by progressive neurological damage and loss of ambulation. Vatiquinone is an investigational, oral, first-in-class inhibitor of 15-lipoxygenase being developed for the treatment of FA.

Method: EPI-2010-006 (NCT01728064) was a randomized, placebo-controlled phase 2 study that examined the efficacy and safety of vatiquinone in ambulatory and nonambulatory adults with FA. This long-term analysis was based on 24-month data from Study 006 compared with FACOMS (2020 data-cut), to investigate vatiquinone’s treatment effect on disease progression. The primary endpoint was the change from baseline in modified Friedreich Ataxia Rating Scale (mFARS). Patients from Study 006 were propensity-score matched to patients from FACOMS. Least squares (LS) mean changes from baseline to 24 months were analyzed by mixed models repeated measures with average treatment effect on the treated weighting. Sensitivity analyses were conducted based on alternative propensity score analysis and statistical analysis methods, using additional matching covariates, and accounting for potential factors influencing disease trajectory.

Results: Following 24 months of vatiquinone treatment in Study 006, patients (n=41; mean age: 28.6 years [min, max: 18, 44 years]) demonstrated a 0.917-point improvement in mFARS (LS mean [SE] change: −0.917 [0.5713]) while the matched FACOMS cohort (n=253, weighted mean age: 28.8 years [min, max: 18, 45 years]) showed a 3.892-point worsening (LS mean [SE] change: 3.892 [0.5681]). This resulted in an LS mean (SE) treatment difference of −4.809 (0.7509) points, favoring vatiquinone (p<0.0001). Sensitivity analyses results were consistent with the primary analysis (all p<0.05), confirming the robustness of the results.

Vatiquinone was well tolerated with a favorable safety profile and no treatment-related serious adverse events

Conclusion: Long-term analyses demonstrate that vatiquinone treatment resulted in a significant slowing of disease progression in ambulatory and nonambulatory adults relative to natural history, supporting preserved function after long-term vatiquinone use.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/long-term-effectiveness-and-tolerability-of-vatiquinone-in-an-adult-friedreichs-ataxia-population/