Omaveloxolone 50mg capsules

Abstract Background Friedreich’s ataxia (FA) is a rare genetic disorder caused by silencing of the frataxin gene (FXN), which leads to multiorgan damage. Nrf2 is a regulator of FXN, which is a modulator of oxidative stress in animals and humans. Omaveloxolone (Omav) is an Nrf2 activator and has been reported to have antioxidative potential in various disease conditions. The present review was conducted to determine the use of Omav, the only FDA-approved treatment for FA. Methods Three electronic databases, Cochrane, PubMed and Google Scholar, were searched with terms such as ‘Omaveloxolone’, ‘Friedreich ataxia’, ‘genetic diseases’, ‘autosomal recessive’, and ‘rare disorders’ using various advanced search filters. Articles were screened, extracted, and assessed for quality, and a qualitative synthesis of the data was performed. The study protocol was registered in PROSPERO (CRD42024531449). Results A total of 201 records were found, with very few published research articles on the topic. Only two randomized clinical trials published in a series of three research articles were included in the current systematic review. Peak load exercise and modified Friedreich’s Ataxia Rating Scale (mFARS) values were considered the major outcome measures for determining the efficacy of 150 mg Omav capsules/day in FA. Exploratory outcome measures, such as low-contrast letter visual acuity test, exercise test, T25-FW, 9-HPT, health-related quality of life, and biochemical tests, were also assessed along with adverse events in all the studies. Conclusion Although, the quality of the articles demonstrated low bias. However, the short duration, small sample size, and missing data, including the values of different measures of mFARS scores in patients, limit the generalizability of the results. Further studies with longer durations and in severe patients with foot deformities are needed to clearly define the efficacy of Omav in FA and to determine the optimal drug for FA patients in India.

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Background: Friedreich ataxia (FA) is a progressive neurodegenerative disorder with significant morbidity and no established disease-modifying therapies. Omaveloxolone, a novel activator of the Nrf2 pathway, targets core disease mechanisms, yet prior evidence relies on non-randomized or early-phase studies. This systematic review aims to evaluate the efficacy and safety of omaveloxolone for individuals with FA based on evidence from randomized controlled trials (RCTs). Methods: We conducted a systematic review in accordance with the Cochrane Handbook and reported it following the PRISMA 2020. The protocol was prospectively registered in PROSPERO (CRD420251115635). Eligible RCTs compared omaveloxolone versus placebo or standard care in genetically confirmed FA. Only RCTs evaluating the approved dose of omaveloxolone (150 mg/day) were considered for the primary analysis. We performed systematic searches across 7 databases and two clinical trial registers without language or date restrictions. Two review authors independently screened titles and abstracts, extracted data, assessed risk of bias using the Cochrane tool, and evaluated the certainty of evidence using the GRADE framework. Results: We identified three RCTs; however, only one multicenter, phase II, double-blind trial (103 participants aged 16–40 years) evaluated the marketed dose and reported complete 48-week results. Low-certainty evidence indicates that omaveloxolone provides little to no improvement in neurological severity (MD –2.40; 95% CI –4.24 to –0.56) and may increase the risk of serious adverse events (RR 1.75; 95% CI 0.43–6.75), while probably having little or no effect on the risk of any adverse events (RR 1.00; 95% CI 0.96–1.04). Omaveloxolone shows minimal to no effects on dexterity, gait speed, or activities of daily living. Conclusion: Based on the current limited evidence from RCTs, omaveloxolone appears to offer minimal clinical benefit for neurological function and daily activities in FA, with uncertainty surrounding the risk of serious adverse events. Larger, long-term trials are needed to better define the role of omaveloxolone in the management of Friedreich ataxia.  

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Friedreich's ataxia (FA) is a rare neurodegenerative disease with multisystemic symptoms that requires multidisciplinary care. This systematic review summarizes available pharmacological and nonpharmacological interventions, their outcomes, and alignment with patient-centered care domains, as well as their impact on these domains. The publication search was conducted in three databases (PubMed, Embase, Cochrane Library) from 2010 to 2025 for human studies. Studies were included if they met predefined eligibility criteria (FA population/pharmacological or nonpharmacological interventions/use of comparator/any outcomes, especially patient reported). All study designs were included. Risk of bias assessment was performed by two reviewers using Cochrane RoB-2 for randomized controlled trials and JBI Critical Appraisal Tools for case reports, case series, and quasi-experimental studies. Results were synthesized narratively. Ninety studies (69 FA only, 21 mixed ataxia) were included. FA-only studies included randomized controlled trials (32%), quasi-experimental studies (35%), and case reports (33%), mostly with small samples (<100) and low-to-moderate bias. Pharmacological interventions (66.7%), mainly disease modifying (93.5%), were more common than nonpharmacological interventions, with the most effective interventions being omaveloxolone (pharmacological), as well as rehabilitation and heart interventions (nonpharmacological). Pharmacological studies often showed biological improvements without clear clinical benefit, whereas nonpharmacological therapies yielded more consistent patient-relevant gains, although evidence was limited. Physical health was the most frequently addressed domain (42.3%), whereas mental health and caregiver aspects were rarely studied (1.8% and 1.4%). No study investigated caregiver burden or economic outcomes. More holistic studies are needed, integrating patient- and caregiver-reported outcomes and combining multiple treatment approaches in larger cohorts. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder with limited treatments. Omaveloxolone, an Nrf2 activator, was approved based on a phase III trial showing modified Friedreich Ataxia Rating Scale (mFARS) improvement. Real-world and long-term data now require synthesis. To perform a single-arm meta-analysis pooling mean change in mFARS from baseline across all published omaveloxolone studies and interpret findings against natural history. Four studies (MOXIe Part 1, Part 2, open-label extension, Italian observational) comprising 248 patients were included. Data were harmonised using standard conversions. A random-effects model was used with subgroup and sensitivity analyses.The pooled mean ΔmFARS was −0.05 (95% CI −2.98 to 2.88; p=0.97). Subgroup analysis showed significant improvement in controlled trials (−2.19; 95% CI −3.12 to −1.27; p<0.00001) and consistent progression in real-world studies (+2.85; 95% CI 1.62 to 4.08; p<0.00001). Sensitivity analyses confirmed robustness. Controlled trials demonstrate significant short-term improvement with omaveloxolone, while real-world data show consistent progression at rates substantially slower than natural history. These complementary findings support a disease-modifying effect of omaveloxolone in FRDA.

Abstract licence: CC BY-NC 4.0

ObjectiveFriedreich ataxia (FA) is a progressive genetic neurodegenerative disorder with no approved treatment. Omaveloxolone, an Nrf2 activator, improves mitochondrial function, restores redox balance, and reduces inflammation in models of FA. We investigated the safety and efficacy of omaveloxolone in patients with FA.MethodsWe conducted an international, double‐blind, randomized, placebo‐controlled, parallel‐group, registrational phase 2 trial at 11 institutions in the United States, Europe, and Australia (NCT02255435, EudraCT2015‐002762‐23). Eligible patients, 16 to 40 years of age with genetically confirmed FA and baseline modified Friedreich's Ataxia Rating Scale (mFARS) scores between 20 and 80, were randomized 1:1 to placebo or 150mg per day of omaveloxolone. The primary outcome was change from baseline in the mFARS score in those treated with omaveloxolone compared with those on placebo at 48 weeks.ResultsOne hundred fifty‐five patients were screened, and 103 were randomly assigned to receive omaveloxolone (n = 51) or placebo (n = 52), with 40 omaveloxolone patients and 42 placebo patients analyzed in the full analysis set. Changes from baseline in mFARS scores in omaveloxolone (−1.55 ± 0.69) and placebo (0.85 ± 0.64) patients showed a difference between treatment groups of –2.40 ± 0.96 (p = 0.014). Transient reversible increases in aminotransferase levels were observed with omaveloxolone without increases in total bilirubin or other signs of liver injury. Headache, nausea, and fatigue were also more common among patients receiving omaveloxolone.InterpretationIn the MOXIe trial, omaveloxolone significantly improved neurological function compared to placebo and was generally safe and well tolerated. It represents a potential therapeutic agent in FA. ANN NEUROL 2021;89:212–225

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AbstractObjectivePrevious studies have demonstrated that suppression of Nrf2 in Friedreich ataxia tissues contributes to excess oxidative stress, mitochondrial dysfunction, and reduced ATP production. Omaveloxolone, an Nrf2 activator and NF‐kB suppressor, targets dysfunctional inflammatory, metabolic, and bioenergetic pathways. The dose‐ranging portion of this Phase 2 study assessed the safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia patients (NCT02255435).MethodsSixty‐nine Friedreich ataxia patients were randomized 3:1 to either omaveloxolone or placebo administered once daily for 12 weeks. Patients were randomized in cohorts of eight patients, at dose levels of 2.5–300 mg/day.ResultsOmaveloxolone was well tolerated, and adverse events were generally mild. Optimal pharmacodynamic changes (noted by changes in ferritin and GGT) were observed at doses of 80 and 160 mg/day. No significant changes were observed in the primary outcome, peak work load in maximal exercise testing (0.9 ± 2.9 W, placebo corrected). At the 160 mg/day dose, omaveloxolone improved the secondary outcome of the mFARS by 3.8 points versus baseline (P = 0.0001) and by 2.3 points versus placebo (P = 0.06). Omaveloxolone produced greater improvements in mFARS in patients that did not have musculoskeletal foot deformity (pes cavus). In patients without this foot deformity, omaveloxolone improved mFARS by 6.0 points from baseline (P < 0.0001) and by 4.4 points versus placebo (P = 0.01) at the 160 mg/day.InterpretationTreatment of Friedreich ataxia patients with omaveloxolone at the optimal dose level of 160 mg/day appears to improve neurological function. Therefore, omaveloxolone treatment is being examined in greater detail at 150 mg/day for Friedreich ataxia.

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The life shortening nature of Friedreich Ataxia (FRDA) demands the search for therapies that can delay, stop or reverse its relentless trajectory. This review provides a contemporary position of drug and gene therapies for FRDA currently in phase 1 clinical trials and beyond. Despite significant scientific advances in the specificity of both compounds and targets developed and investigated, challenges remain for the advancement of treatments in a limited recruitment population. Currently therapies focus on reducing oxidative stress and improving mitochondrial function, modulating frataxin controlled metabolic pathways and gene replacement and editing. Approval of omaveloxolone, the first treatment for individuals with FRDA aged 16 years and over, has created much excitement for both those living with FRDA and those that care for them. The process of approval of omaveloxolone by the US Food and Drug Administration highlighted the importance of sensitive outcome measures and the significant role of data from natural history studies.

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ABSTRACTBackgroundMOXIe 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 placebo‐controlled 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.ObjectiveThe 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.MethodsWe 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.ResultsThe noninferiority testing demonstrated that the difference in mFARS between omaveloxolone and placebo observed at the end of placebo‐controlled MOXIe part 2 (−2.17 ± 1.09 points) was preserved after 72 weeks in the extension (−2.91 ± 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.ConclusionsThese results support the positive results of MOXIe part 2 and indicate a persistent benefit of omaveloxolone treatment on disease course in Friedreich's ataxia. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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