Long-Term Safety and Tolerability of Omaveloxolone in Patients With Friedreich Ataxia: Up to 6-Year Data From the MOXIe Open-Label Extension

Topic:

Clinical Trials

Poster Number: 298 T

Author(s):

Theresa Zesiewicz, MD, MD, University of South Florida Ataxia Research Center, Tampa, Florida, USA, Susan Perlman, MD, University of California, Los Angeles, Martin B. Delatycki, Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, J. Chad Hoyle, Ohio State University College of Medicine, Sylvia Boesch, MD, Medical University of Innsbruck, Wolfgang Nachbauer, MD, PhD, Medical University of Innsbruck, Paola Giunti, MD, PhD, University College Hospital, George Wilmot, MD, PhD, Emory University School of Medicine, SH Subramony, MD, University of Florida Health, Katherine Mathews, MD, University of Iowa, Iowa City, Iowa, USA, Syed Farooq, Biogen International GmbH, Shobhana Natarajan, PhD, Biogen, Inc., Rose M. Domingo-Horne, MD, Biogen, Inc., Andre Arizpe, PharmD, Biogen, Inc., Jonathan Smith, MSc, Biogen Idec Ltd, Nicolas Folschweiller, Biogen, David Lynch, MD, PhD, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

Background: Omaveloxolone is an Nrf2 activator approved for the treatment of Friedreich ataxia (FA) in patients aged ≥16 years based on the MOXIe study and its open-label extension (OLE; NCT02255435). In MOXIe Part 2, the majority of treatment-emergent adverse events (TEAEs) were mild to moderate in severity; TEAEs more commonly reported with omaveloxolone versus placebo included elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT), headache, nausea, abdominal pain, fatigue, musculoskeletal pain, and diarrhea.

Objective: To evaluate the long-term safety and tolerability of omaveloxolone treatment in the MOXIe OLE.

Methods: Patients who completed MOXIe Part 1 or 2 were eligible to receive omaveloxolone in the OLE to assess safety and tolerability in the overall omaveloxolone population comprising those considered treatment naive (all patients from Part 1 and placebo-treated patients from Part 2) and those who received omaveloxolone in Part 2 and continued treatment in the OLE. TEAEs from Baseline (extension Day 1) of the OLE through data cutoff (February 27, 2025; up to 6 years of follow-up) are presented. Change from Baseline in clinical laboratory parameters are presented through extension Week 264 (≈5 years).

Results: In the overall omaveloxolone population (N=149), 146 patients (98.0%) experienced TEAEs, most of which were mild or moderate in severity; 80 patients (53.7%) had TEAEs deemed related to study treatment. Overall, 25 (16.8%) experienced SAEs; 1 event of pulmonary embolism was considered related to treatment, and all SAEs occurred in ≤2 patients (mostly in single patients). The most common TEAEs reported as related to study treatment were increased ALT (18.1%), nausea (11.4%), increased AST (7.4%), abdominal pain (6.0%), headache (6.0%), fatigue (5.4%), diarrhea (4.7%), increased BNP (2.7%), muscle spasms (2.7%), and myalgia (2.7%). ALT and AST elevations generally occurred early in the OLE, were transient, and were not accompanied by increases in total bilirubin, consistent with findings from MOXIe Part 2.

Conclusions: This updated analysis of the MOXIe OLE provides up to 6 years of continuous long-term safety and tolerability data regarding omaveloxolone use in patients with FA. Safety findings were consistent with the previously known safety profile.