eprintid: 10161377 rev_number: 7 eprint_status: archive userid: 699 dir: disk0/10/16/13/77 datestamp: 2022-12-06 15:19:29 lastmod: 2022-12-06 15:19:29 status_changed: 2022-12-06 15:19:29 type: article metadata_visibility: show sword_depositor: 699 creators_name: Lynch, David R creators_name: Chin, Melanie P creators_name: Boesch, Sylvia creators_name: Delatycki, Martin B creators_name: Giunti, Paola creators_name: Goldsberry, Angie creators_name: Hoyle, J Chad creators_name: Mariotti, Caterina creators_name: Mathews, Katherine D creators_name: Nachbauer, Wolfgang creators_name: O'Grady, Megan creators_name: Perlman, Susan creators_name: Subramony, SH creators_name: Wilmot, George creators_name: Zesiewicz, Theresa creators_name: Meyer, Colin J title: Efficacy of Omaveloxolone in Friedreich's Ataxia: Delayed-Start Analysis of the MOXIe Extension ispublished: inpress divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F84 note: Copyright © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. abstract: 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 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. 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 (-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. 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. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. date: 2022-11-29 date_type: published publisher: Wiley official_url: https://doi.org/10.1002/mds.29286 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1993355 doi: 10.1002/mds.29286 medium: Print-Electronic lyricists_name: Giunti, Paola lyricists_id: PGIUN65 actors_name: Meyer, Carly actors_name: Flynn, Bernadette actors_id: CMMEY23 actors_id: BFFLY94 actors_role: owner actors_role: impersonator funding_acknowledgements: NONE [Reata Pharmaceutical] full_text_status: public publication: Movement Disorders event_location: United States issn: 0885-3185 citation: Lynch, David R; Chin, Melanie P; Boesch, Sylvia; Delatycki, Martin B; Giunti, Paola; Goldsberry, Angie; Hoyle, J Chad; ... Meyer, Colin J; + view all <#> Lynch, David R; Chin, Melanie P; Boesch, Sylvia; Delatycki, Martin B; Giunti, Paola; Goldsberry, Angie; Hoyle, J Chad; Mariotti, Caterina; Mathews, Katherine D; Nachbauer, Wolfgang; O'Grady, Megan; Perlman, Susan; Subramony, SH; Wilmot, George; Zesiewicz, Theresa; Meyer, Colin J; - view fewer <#> (2022) Efficacy of Omaveloxolone in Friedreich's Ataxia: Delayed-Start Analysis of the MOXIe Extension. Movement Disorders 10.1002/mds.29286 <https://doi.org/10.1002/mds.29286>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10161377/1/Efficacy%20of%20Omaveloxolone%20in%20Friedreichs%20Ataxia.pdf