Interim Analysis of mFARS Trajectories Across 5 Years in the MOXIe Extension: Impact of Omaveloxolone Initiation Timing in Friedreich Ataxia

Topic:

Clinical Trials

Poster Number: 297 T

Author(s):

Theresa Zesiewicz, MD, MD, University of South Florida Ataxia Research Center, Tampa, Florida, USA, David Lynch, MD, PhD, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA, Claudia Yang Santos, PhD, Biogen, Inc., Susie Sinks, Biogen, Inc., Syed Farooq, Biogen International GmbH, Jonathan Smith, MSc, Biogen Idec Ltd, Shobhana Natarajan, PhD, Biogen, Inc., Nicolas Folschweiller, Biogen

Background: Omaveloxolone, an Nrf2 activator, is approved for the treatment of Friedreich ataxia (FA) in patients aged ≥16 years based on findings from the MOXIe study and its open-label extension (OLE; NCT02255435). In MOXIe Part 2, patients treated with omaveloxolone 150 mg QD showed a statistically significant benefit in neurological function compared with placebo at 48 weeks (≈1 year), as assessed by the modified Friedreich Ataxia Rating Scale (mFARS), with lower scores indicating less impairment. Patients who completed MOXIe Part 2 were eligible to enroll in the OLE for longer-term follow-up.

Objective: Compare mFARS score trajectories between patients who initially received omaveloxolone in MOXIe Part 2 and patients who started omaveloxolone 1 year later in the OLE.

Methods: This analysis used data from all randomized participants to compare changes in mFARS from baseline (Day 1 of MOXIe Part 2) between participants who received omaveloxolone throughout the study (omaveloxolone-omaveloxolone) and those who initiated omaveloxolone 1 year later in the OLE (placebo-omaveloxolone). The estimated LSM changes from baseline in mFARS scores and the LSM differences (95% CIs) between groups are presented for each group at the end of MOXIe Part 2 (Week 48) and during the OLE (through extension Week 240). The data cut was in February 2025.

Results: The number of participants in the omaveloxolone-omaveloxolone group was 42 at Week 48 of MOXIe Part 2 and 28 at Week 240 of the OLE; for the placebo-omaveloxolone group, numbers were 50 and 28, respectively. Reasons for changes in patient follow-up numbers will be discussed in the presentation. The LSM (95% CI) difference in mFARS scores between omaveloxolone-omaveloxolone and placebo-omaveloxolone groups varied across time points, with differences (omaveloxolone-omaveloxolone minus placebo-omaveloxolone) of −1.86 (−3.84 to 0.11) at MOXIe Part 2 Week 48 and −0.89 (−3.17 to 1.40) at OLE baseline, 1.00 (−1.58 to 3.58) at OLE Week 48, −1.27 (−3.93 to 1.40) at OLE Week 96, −2.35 (−4.96 to 0.27) at OLE Week 144, −2.52 (−5.05 to 0.01) at OLE Week 192, and −0.86 (−3.86 to 2.15) at OLE Week 240.

Conclusions: The omaveloxolone-omaveloxolone group that started treatment 1 year before the placebo-omaveloxolone group showed numerically slower mFARS progression, relatively. Nevertheless, all patients receiving omaveloxolone experienced sustained benefit in slowing of mFARS decline throughout the analysis period.