| Neurogenetics | Rare Neurological Diseases  

Approval of Omaveloxolone as the First Specific Treatment for Friedreich's Ataxia

Friedreich´s Ataxia (FA) is the most common hereditary ataxia in Europe and is a progressive, highly disabling disease. Recently, the European Medicines Agency approved omaveloxolone as the first specific medical therapy for the treatment of FA in patients aged 16 years and older.

Friedreich's Ataxia (FA) is the most common hereditary ataxia in the European population. FA presents with progressive, predominantly afferent ataxia, often accompanied by non-neurological features such as cardiomyopathy, scoliosis, foot deformities, and diabetes mellitus. The disease is caused by a deficiency of the mitochondrial protein frataxin. Most patients carry a biallelic GAA repeat expansion in the first intron of the frataxin gene.

Following the U.S. Food & Drug Administration, the European Medicines Agency recently approved omaveloxolone for the treatment of FA in individuals 16 years of age and older. Omaveloxolone activates the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, a critical regulator of cellular redox homeostasis and mitochondrial function that is pathologically suppressed in FA1.

The approval of omaveloxolone was based on the results of the MOXIe trial, a double-blind, randomized, placebo-controlled study that enrolled 103 FA patients in the United States, Europe and Australia2. The primary endpoint of MOXIe was the change in the neurological outcome measure, the modified Friedreich's Ataxia Rating Scale (mFARS). At the end of the 48-week treatment period, the verum group showed a significant change in mFARS of -2.40 ± 0.96 points compared to the placebo group2. Following the placebo-controlled phase, patients were enrolled in an open-label extension in which all patients received omaveloxolone. The delayed-start analysis of this phase showed a sustained benefit for those who started omaveloxolone earlier compared to those who started in the extension phase3.

Currently, omaveloxolone is the only drug approved for the treatment of FA1.

Key Points:

  • Friedreich´s Ataxia (FA) is the most common hereditary ataxia in Europe and is a progressive, highly disabling disease.
  • The drug omaveloxolone activates the Nrf2 pathway, a critical regulator of cellular redox homeostasis and mitochondrial function that is pathologically suppressed in FA.
  • Omaveloxolone was recently approved by the European Medicines Agency for the treatment of FA in patients aged 16 years and older, based on the findings of the MOXIe trial.
  • In the MOXIe trial, patients receiving omaveloxolone over a period of 48 weeks showed a significant change of -2.40 ± 0.96 points in the neurological outcome measure mFARS as compared to the placebo group.

References:

  1. Boesch, S. & Indelicato, E. Approval of omaveloxolone for Friedreich ataxia. Nat. Rev. Neurol. 2024 1–2 (2024) doi:10.1038/s41582-024-00957-9.
  2. Lynch, D. R. et al. Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study). Ann. Neurol.89, 212–225 (2021).
  3. Lynch, D. R. et al. Efficacy of Omaveloxolone in Friedreich’s Ataxia: Delayed-Start Analysis of the MOXIe Extension. Mov. Disord.38, 313–320 (2023).

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