{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:20:05Z","timestamp":1793146805810,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,11,10]],"date-time":"2018-11-10T00:00:00Z","timestamp":1541808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Reata Pharmaceutical"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Previous studies have demonstrated that suppression of Nrf2 in Friedreich ataxia tissues contributes to excess oxidative stress, mitochondrial dysfunction, and reduced\n                      <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\n                      production. Omaveloxolone, an Nrf2 activator and\n                      <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">kB<\/jats:styled-content>\n                      suppressor, targets dysfunctional inflammatory, metabolic, and bioenergetic pathways. The dose\u2010ranging portion of this Phase 2 study assessed the safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia patients (\n                      <jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>\n                      02255435).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixty\u2010nine Friedreich ataxia patients were randomized 3:1 to either omaveloxolone or placebo administered once daily for 12\u00a0weeks. Patients were randomized in cohorts of eight patients, at dose levels of 2.5\u2013300\u00a0mg\/day.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Omaveloxolone was well tolerated, and adverse events were generally mild. Optimal pharmacodynamic changes (noted by changes in ferritin and\n                      <jats:styled-content style=\"fixed-case\">GGT<\/jats:styled-content>\n                      ) were observed at doses of 80 and 160\u00a0mg\/day. No significant changes were observed in the primary outcome, peak work load in maximal exercise testing (0.9\u00a0\u00b1\u00a02.9\u00a0W, placebo corrected). At the 160\u00a0mg\/day dose, omaveloxolone improved the secondary outcome of the\n                      <jats:styled-content style=\"fixed-case\">mFARS<\/jats:styled-content>\n                      by 3.8 points versus baseline (\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      =\n                      <jats:italic>\u00a0<\/jats:italic>\n                      0.0001) and by 2.3 points versus placebo (\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      =\n                      <jats:italic>\u00a0<\/jats:italic>\n                      0.06). Omaveloxolone produced greater improvements in\n                      <jats:styled-content style=\"fixed-case\">mFARS<\/jats:styled-content>\n                      in patients that did not have musculoskeletal foot deformity (pes cavus). In patients without this foot deformity, omaveloxolone improved\n                      <jats:styled-content style=\"fixed-case\">mFARS<\/jats:styled-content>\n                      by 6.0 points from baseline (\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      &lt;\n                      <jats:italic>\u00a0<\/jats:italic>\n                      0.0001) and by 4.4 points versus placebo (\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      =\n                      <jats:italic>\u00a0<\/jats:italic>\n                      0.01) at the 160\u00a0mg\/day.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Treatment of Friedreich ataxia patients with omaveloxolone at the optimal dose level of 160\u00a0mg\/day appears to improve neurological function. Therefore, omaveloxolone treatment is being examined in greater detail at 150\u00a0mg\/day for Friedreich ataxia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.660","type":"journal-article","created":{"date-parts":[[2018,11,11]],"date-time":"2018-11-11T00:09:44Z","timestamp":1541894984000},"page":"15-26","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":177,"title":["Safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia"],"prefix":"10.1002","volume":"6","author":[{"given":"David R.","family":"Lynch","sequence":"first","affiliation":[{"name":"Division of Neurology The Children's Hospital of Philadelphia 502 Abramson Research Center 3615 Civic Center Blvd Philadelphia Pennsylvania 19104\u20104318"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Farmer","sequence":"additional","affiliation":[{"name":"Friedreich's Ataxia Research Alliance 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