For March 2021, we have selected: Lynch D.R. et al. Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study). Ann Neurol 2021; 89:212-225. doi: 10.1002/ana.25934.
Our research of the month is an international, double-blind, randomized, placebo-controlled, parallel-group, registrational phase 2 trial at 11 institutions in the United States, Europe, and Australia testing Omaveloxolone for the treatment of the Friedreich ataxia (FA). It was labelled the MOXIe trial. This agent is an Nrf2 activator; therefore it improves mitochondrial function, restores redox balance, and reduces inflammation in models of FA.
This study represents a significant step in the landscape of this progressive genetic neurodegenerative disorder, which does not have any approved treatment.
The authors established the following selection criteria: patient with FA (genetically confirmed FA) between 16 and 40 year of age and with a baseline modified Friedreich’s Ataxia Rating Scale (mFARS) scores between 20 and 80.
103 patients were recruited and randomized 1:1 to placebo (52) or 150mg per day of omaveloxolone (51).
The patients were followed up at 48 weeks when the primary outcome was change from baseline in the mFARS score in those treated with omaveloxolone compared with those on placebo. Of note some patients were lost at follow up and only 40 omaveloxolone patients and 42 placebo patients took part in the complete study.
The clinical outcome at 48 weeks showed changes from baseline in mFARS scores in both groups (omaveloxolone patients = −1.55 ± 0.69; placebo patients = 0.85 ± 0.64) but with a statistically significant difference between treatment groups of –2.40 ± 0.96 (p = 0.014).
Side effects in the omavexolone group were: transient reversible increases in aminotransferase levels without signs of liver injury, headache, nausea and fatigue.
The main limitations of our study of the month included the small sample size, modest duration, and possible limitations of the generalizability of the results. However, it is important to notice that FA is a rare and progressive disease and, thus, it is very difficult to have a larger cohort or longer duration. Overall, this trial showed a specific efficacy of the omaveloxolone improving neurological function of FA patients compared to placebo after 48 weeks of therapy, which was also associated with a reasonable safety. Further studies, especially in paediatric patients, are necessary to develop larger cohort and to study the clinical outcome of a longer duration of therapy.