CHAMPION-NMOSD Extension Study Supports Long-Term Efficacy of Ravulizumab in NMOSD

New long-term extension data from the phase 3 CHAMPION-NMOSD (NCT04201262) trial showed that patients with antiaquaporin (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD) treated with ravulizumab-cwvz (Ultomiris; Alexion) experienced no adjudicated on-trial relapses and most displayed stable or improvement in disability.¹

Among 58 patients with NMOSD enrolled, 56 entered and 55 completed the long-term extension, with a median follow-up of 170.3 weeks (range, 11–243) totaling 189.7 patient-years. Presented at the 2025 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, held September 24-26, in Barcelona, Spain, researchers reported that throughout the primary treatment period and long-term extension, no patient who received ravulizumab-cwvz had an adjudicated on-trial relapse. Notably, ravulizumab-cwvz-treated patients maintained a 98.9% relative reduction in relapse risk compared with placebo (95% CI, 91.8-100; P <.0001).

Presented by lead author Sean J. Pittock, MD, the director of the Center for Multiple Sclerosis and Autoimmune Neurology at Mayo Clinic, the data showed that most treated patients (n = 55) had stable or improved Hauser Ambulation Index (HAI) scores, with 81.0% remaining stable (n = 47) and 13.8% showing improvement (n = 8). In addition, investigators observed that 91.4% of patients (n = 53) treated with ravulizumab-cwvz experienced no clinically meaningful worsening on the Expanded Disability Status Scale (EDSS).

READ MORE: International Panel Revises NMOSD Diagnostic Criteria Based on Evidence-Based Consensus

In CHAMPION-NMOSD, a phase 3, open-label, external, placebo-controlled trial, participants received an intravenous, weight-based loading dose of ravulizumab-cwvz on day 1, followed by a maintenance dose on day 15 and then once every 8 weeks. Patients who completed the primary treatment period, up to 2.5 years, were eligible to enter the long-term extension. The primary end points were time to first adjudicated on-trial relapse and relapse risk reduction. Secondary end points included adjudicated on-trial relapse rate, change from baseline in HAI and EDSS scores, and safety.

Out of 27 patients who took immunosuppressive therapy at baseline, 63.0% reduced their dose or discontinued at least 1 immunosuppressive therapy (n = 17). Researchers reported treatment-emergent adverse events (TEAEs) and serious TEAEs in 94.8% and 27.6% of participants, respectively. Most patients who experienced TEAEs were grade 1 (86.2%) and unrelated to treatment with ravulizumab-cwvz (94.8%).

Authors noted that only 1 patient withdrew from the study drug because of TEAEs and only 2 cases of meningococcal infection occurred during the primary treatment period, with none reported in the long-term extension study. Investigators reported that 1 cardiovascular-related death occurred during the long-term extension portion of the trial unrelated to ravulizumab-cwvz.

Ravulizumab-cwvz, a terminal compliment C5 inhibitor, was approved by the FDA for the treatment of adults with AQP4 antibody-positive NMOSD based on the results of the primary treatment period of CHAMPION-NMOSD in March 2024.² The safety profile of ravulizumab-cwvz remained consistent with prior findings, and no additional cases of meningococcal infection were observed beyond the 2 that occurred during the primary treatment period. Overall, authors noted that these data support the sustained long-term efficacy of ravulizumab-cwvz in adult patients with AQP4 antibody-positive NMOSD.

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REFERENCES
1. Pittock S, Barnett M, Bennett JL, et al. Long-term efficacy and safety of ravulizumab in anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder: final analysis of the phase 3 CHAMPION-NMOSD trial. Presented at ECTRIMS Congress; September 24-26, 2025; Barcelona, Spain. Abstract O109.
2. ULTOMIRIS® (ravulizumab-cwvz) approved in the US for the treatment of adults with neuromyelitis optica spectrum disorder (NMOSD). News Release. Alexion Pharma. Published March 25, 2024. Accessed March 25, 2024. https://www.businesswire.com/news/home/20240325711806/en/ULTOMIRIS%C2%AE-ravulizumab-cwvz-approved-in-the-US-for-the-treatment-of-adults-with-neuromyelitis-optica-spectrum-disorder-NMOSD