Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Reata Pharmaceuticals, Dallas, TX, USA.
Ann Neurol. 2021 Feb;89(2):212-225. doi: 10.1002/ana.25934. Epub 2020 Nov 5.
Friedreich 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.
We 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.
One 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.
In 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.
弗里德赖希共济失调（FA）是一种进行性遗传性神经退行性疾病，尚无批准的治疗方法。Nrf2 激活剂 omaveloxolone 可改善线粒体功能、恢复氧化还原平衡并减少 FA 模型中的炎症。我们研究了 omaveloxolone 在 FA 患者中的安全性和疗效。
我们在美国、欧洲和澳大利亚的 11 个机构进行了一项国际、双盲、随机、安慰剂对照、平行分组、注册 2 期试验（NCT02255435，EudraCT2015-002762-23）。符合条件的患者为 16 至 40 岁，遗传确诊的 FA，基线改良 Friedreich's Ataxia Rating Scale（mFARS）评分在 20 至 80 之间，随机分为 1:1 接受安慰剂或 150mg 每天一次的 omaveloxolone 治疗。主要结局为 omaveloxolone 治疗组与安慰剂组在 48 周时的 mFARS 评分与基线相比的变化。
155 名患者接受了筛查，103 名患者被随机分配接受 omaveloxolone（n = 51）或安慰剂（n = 52），共有 40 名 omaveloxolone 患者和 42 名安慰剂患者在全分析集中进行了分析。omaveloxolone（-1.55±0.69）和安慰剂（0.85±0.64）患者的 mFARS 评分与基线相比的变化表明治疗组之间的差异为-2.40±0.96（p=0.014）。omaveloxolone 治疗后观察到氨基转移酶水平短暂可逆升高，总胆红素或其他肝损伤迹象无增加。头痛、恶心和疲劳在接受 omaveloxolone 治疗的患者中也更为常见。
在 MOXIe 试验中，与安慰剂相比，omaveloxolone 显著改善了神经功能，总体上安全且耐受良好。它代表了 FA 的一种潜在治疗药物。
