Efficacy of Omaveloxolone in Friedreich's Ataxia: Delayed‐Start Analysis of the MOXIe Extension

Abstract

A BS TRACT: Background: MOXIe was a two-part study evaluating the safety and efficacy of omaveloxolone in patients with Friedreich's ataxia, a rare, progressive neurological disease with no proven therapy. MOXIe part 2, a randomized double-blind placebocontrolled trial, showed omaveloxolone significantly improved modified Friedreich's Ataxia Rating Scale (mFARS) scores relative to placebo. Patients who completed part 1 or 2 were eligible to receive omaveloxolone in an open-label extension study. Objective: The delayed-start study compared mFARS scores at the end of MOXIe part 2 with those at 72 weeks in the open-label extension period (up to 144 weeks) for patients initially randomized to omaveloxolone versus those initially randomized to placebo. Methods: We performed a noninferiority test to compare the difference between treatment groups (placebo to omaveloxolone versus omaveloxolone to omaveloxolone) using a single mixed model repeated measures (MMRM) model. In addition, slopes of the change in mFARS scores were compared between both groups in the open-label extension.Results: The noninferiority testing demonstrated that the difference in mFARS between omaveloxolone and placebo observed at the end of placebo-controlled MOXIe part 2 (À2.17 AE 1.09 points) was preserved after 72 weeks in the extension (À2.91 AE 1.44 points). In addition, patients previously randomized to omaveloxolone in MOXIe part 2 continued to show no worsening in mFARS relative to their extension baseline through 144 weeks. Conclusions: These results support the positive results of MOXIe part 2 and indicate a persistent benefit of omaveloxolone treatment on disease course in Friedreich's ataxia.

Evaluating mFARS in pediatric Friedreich's ataxia: Insights from the FACHILD study

“…In adults, the scale is a sensitive and relevant tool to assess neurological disease progression. 8,9 Upper Limbs (FARS B)…”

Clinical Reasoning: A 48-Year-Old Man With Spasticity and Progressive Ataxia

“…14 Treatment is symptomatic, and omaveloxolone, an activator of the mitochondrial Nrf2 pathway, was FDA-approved in February 2023 as a disease-modifying therapy for FRDA. 15 Genetic counseling is also encouraged for patients and families. Although prenatal testing exists, predicting the clinical phenotype based on GAA repeat length alone is difficult.…”

Longitudinal changes of SARA scale in Friedreich ataxia: Strong influence of baseline score and age at onset

“…[13][14][15][16] Conversely, SARA has been chosen as one of the primary outcome measures in the EFACTS prospective study. 11 Both scales have been largely used in interventional clinical trials for FA, [17][18][19] and statistical properties of SARA have been analyzed both in SCA [20][21][22][23] and in FA studies. 11,21,[24][25][26][27][28] In the present study, we aimed to analyze distribution and longitudinal changes of SARA total score and its item scores in a homogeneous cohort of patients with typicalonset FA.…”

“…Conversely, SARA has been chosen as one of the primary outcome measures in the EFACTS prospective study 11 . Both scales have been largely used in interventional clinical trials for FA, 17–19 and statistical properties of SARA have been analyzed both in SCA 20–23 and in FA studies 11,21,24–28 …”