Phase 3 CHAMPION-NMOSD Trial With Ravulizumab Significantly Lowers Risk of Relapse


Updated results to the phase 3 CHAMPION-NMOSD trial of ravulizumab showed significantly lower HAI score worsening following treatment.

director, Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic

Sean J. Pittock, MD

New findings from the phase 3 CHAMPION-NMOSD trial (NCT04201262) showed that ravulizumab-cwvz (Ultomiris; Alexion) not only reduced the risk of relapse but also significantly lowered Hauser Ambulation Index (HAI) score worsening compared with placebo in patients with anti-aquaporin (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD).1

All told, there were no patients that had adjudicated relapses with ravulizumab versus 20 with placebo (relapse risk reduction [RRR], 98.6%; P <.0001). The annualized relapse rate (ARR) of those on the therapy was 0.00 (upper 95% CI, 0.04), which was superior to a predefined comparator ARR (0.25; P <.0001). There were fewer patients who experienced clinically important HAI score worsening with ravulizumab (2 out of 58 patients; 3.4%) compared with placebo (11/47; 23.4%; P = .023), demonstrated by ORs of 0.16 (95% CI, 0.03–0.77).

The results were presented as an oral presentation at the 2023 American Academy of Neurology (AAN) Annual Meeting, April 22-27, in Boston, Massachusetts, by lead author Sean J. Pittock, MD, director, Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic. These updated analyses continue to support the critical benefits of ravulizumab, a long-acting C5 complement inhibitor, in AQP4 Ab+ NMOSD treatment and its potential to substantially reduce the risk of relapse in a broad range of patients.2

The trial was an open-label, multicenter study that evaluated the efficacy and safety of ravulizumab in 58 adult patients with anti-AQP4 NMOSD who had at least 1 attack or relapse in the 12 months prior to the screening visit. The participants also had Expanded Disability Status Scale scores of 7 or less, had body weight of at least 40 kg at trial entry, and were allowed to stay on stable supportive immunosuppressive therapy for the duration of the trial.

The patients received a weight-based intravenous loading dose of ravulizumab, then a maintenance dose on day 15 following every 8 weeks after. Eculizumab (Soliris; Alexion) availability precluded concurrent placebo control and the PREVENT trial (NCT01892345) placebo arm was used as an external comparator. Propensity scores accounted for potential differences in patient characteristics between the arms.

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The primary endpoint was time to first adjudicated on-trial relapse and RRR, while the secondary efficacy endpoints included adjudicated on-trial ARR and clinically important worsening from baseline in HAI score. The median for follow-up was 73.5 (range, 11.0-117.7) weeks for all ravulizumab-treated patients and 36.0 (range, 1.9-117.7) weeks for placebo (n = 47).

Treatment-emergent adverse events (AEs) were observed in 93.1% of patients on ravulizumab and serious AEs in 13.8% of patients. Only 2 vaccinated patients experienced meningococcal infection (2.4 out of 100 patient-years). Both recovered with no sequelae and one continued with the trial. There were no deaths were reported. The efficacy and safety data remained consistent with the primary treatment period despite the longer follow-up (median treatment duration, 90.9 weeks).

Ravulizumab was originally FDA-approved in 2018 to treat adults with paroxysmal nocturnal hemoglobinuria and was later expanded to include children and adolescents in 2021. The treatment binds the same complement component 5 epitope as eculizumab and its longer half-life enables an extended dosing interval, 8 versus 2 weeks.

In May 2022, AstraZeneca announced that ravulizumab met its primary end point of time to first on-trial relapse, with no relapses observed in 58 patients (RRR, 98.7%) with QP4 Ab+ NMOSD over a median treatment duration of 73 weeks. "Every NMOSD relapse can have debilitating and irreversible consequences, so reducing relapses is critical,” Pittock said in a statement at the time.3 “Patients on Ultomiris remained relapse free over a median treatment duration of 73 weeks in the trial."

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1. Pittock S, Barnett M, Bennett J, et al. Efficacy and safety of ravulizumab in adults with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder: outcomes from the phase 3 CHAMPION-NMOSD trial. Presented at: 2023 AAN Annual Meeting; April 22-27, Boston, Massachusetts. Abstract 002.
2. Alexion advances commitment to transform patient outcomes in rare neurological diseases at AAN 2023. News Release. Published March 2, 2023. Accessed April 22, 2023.
3. Ultomiris met primary end point in CHAMPION-NMOSD phase 3 trial in adults with neuromyeltis optica spectrum disorder. News release. AstraZeneca. May 5, 2022. Accessed April 22, 2023.
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