Literature Review Demonstrates Ravulizumab’s Superior Efficacy Over Other Approved NMOSD Treatments


In comparison to previously approved treatments like satralizumab and inebilizumab, ravulizumab-treated patients performed significant better on outcomes of first relapse and time to first relapse.

Stacey L. Clardy, MD, PhD, an autoimmune neurologist and associate professor at the University of Utah

Stacey L. Clardy, MD, PhD

In a literature review assessing clinical trials of approved therapies for neuromyelitis optica spectrum disorder (NMOSD), findings revealed that ravulizumab (Ultomiris; Alexion), the most recently approved medication, was more efficacious at preventing relapse than satralizumab (Enspryng; Genentech) and inebilizumab (Uplizna; Horizon Therapeutics). It also demonstrated a comparable profile to eculizumab (Soliris; Alexion), the first approved agent for (NMOSD), even when used in combination with immunosuppressants.

Led by Stacey L. Clardy, MD, PhD, an autoimmune neurologist and associate professor at the University of Utah, the study data were presented at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado. All told, results showed that ravulizumab was associated with a more than 90% reduction in experiencing a first relapse relative to satralizumab (HR, 0.08; 95% CI, 0.01-0.55) and inebilizumab (HR, 0.09; 95% CI, 0.02-0.57). Time to first relapse (TTFR), another end point of interest, was comparable between ravulizumab and eculizumab (HR, 0.86; 95% CI, 0.16-4.52).

Ravulizumab, a complement C5 inhibitor, was approved for the treatment of patients who are aquaporin-4-antibody positive (AQP4) NMOSD in March 2024. With the decision, it became the fourth approved therapy, following behind eculizumab, inebilizumab, and satralizumab. Ravulizumab’s approval was based on the phase 3 CHAMPION-NMOSD trial (NCT04201262), where the agent met its primary end point of time to first on-trial relapse, with no relapses observed in 58 patients with NMOSD over a median treatment duration of 73 weeks.2

CHAMPION-NMOSD, one of the trials used in the analysis, used an external placebo control arm from the PREVENT trial (NCT01892345), a phase 3 study that evaluated eculizumab. The remaining evidence based used by Clardy et al consisted of randomized controlled trials for all interventions. All analyses were performed in a Bayesian framework.

READ MORE: Complement Inhibitors Ravulizumab and Eculizumab Impact Measures of Neuroaxonal Damage

All told, findings for annualized relapse rate (ARR), another end point of interest, were consistent with TTFR. For ravulizumab, the rate of relapse was 98% lower than with satralizumab (RR, 0.02; 95% CI, 0.00-0.42) and inebilizumab (RR, 0.02; 95% CI, 0.00-0.38). In combination with immunosuppressants, ravulizumab showed an 85% reduction in first relapse relative to satralizumab (HR, 0.15; 95% CI, 0.03-0.78).

For years, NMOSD, a central nervous system inflammatory demyelinating disease, was managed through standard immunosuppressives such as prednisolone, azathioprine, and mycophenolate mofetil. Patients on these medications still would experience relapse because of low efficacy and low adherence related to severe adverse events. Monoclonal antibodies like eculizumab, satralizumab, and inebilizumab, which were introduced in 2019, are claimed to have higher efficacy and lower AEs, but at much higher cost than the standard immunosuppressive drugs, making them less accessible.

In CHAMPION-NMOSD, the median follow-up time was 73.5 weeks for ravulizumab-cwvz and 36.0 weeks for placebo. At the conclusion of the trial, the ARR of 0.00 with ravulizumab-cwvz was superior to both the predefined comparator ARR of 0.25 and the placebo ARR of 0.42 (95% CI, 0.27-0.66; P <.0001). Additionally, only 3.4% of patients on ravulizumab-cwvz experienced clinically important worsening in HAI score compared with 23.4% of those on placebo (odds ratio [OR], 0.16; 95% CI, 0.03-0.77; P = .023).2

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1. Clardy S, Pittock S, Aktas O, et al. Indirect treatment comparison of ravulizumab versus approved treatment options for adults with aquaporin-4 immunoglobulin G-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD). Presented at: 2024 AAN Annual Meeting; April 13-18; 002511
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 April 26, 2024.
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