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
Sean Pittock1, Michael Barnett2, Jeffrey Bennett3, Achim Berthele4, Jérôme de Sèze5, Michael Levy6, Ichiro Nakashima7, Celia Oreja Guevara8, Jacqueline Palace9, Friedemann Paul10, Carlo Pozzilli11, Kerstin Allen12, Yasmin Mashhoon12, Marcus Yountz13, Ho Jin Kim14
1Department of Neurology, Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USA, 2Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia; Department of Neurology, Royal Prince Alfred Hospital, Sydney, NSW, Australia, 3Departments of Neurology and Ophthalmology, Programs in Neuroscience and Immunology, University of Colorado, Aurora, CO, USA, 4Department of Neurology, School of Medicine, Technical University of Munich, Munich, Germany, 5Department of Neurology and Clinical Investigation Center, CHU de Strasbourg, Strasbourg, France, 6Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA, 7Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan; Division of Neurology, Tohoku Medical and Pharmaceutical University, Sendai, Japan, 8Department of Neurology, Hospital Clínico Universitario San Carlos, IdISCC, Madrid, Spain; Department of Medicine, Universidad Complutense de Madrid, Madrid, Spain, 9Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK, 10Experimental and Clinical Research Center and NeuroCure Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité – Universitätsmedizin Berlin, Berlin, Germany, 11Department of Human Neuroscience, University Sapienza, Rome, Italy, 12Alexion, AstraZeneca Rare Disease, Boston, MA, USA, 13Alexion, AstraZeneca Rare Disease, Boston, MA, USA *At the time this research was conducted., 14Department of Neurology, National Cancer Center, Goyang, South Korea

To report efficacy and safety of ravulizumab in anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder AQP4+ NMOSD.


Ravulizumab binds the same complement component 5 epitope as eculizumab; its longer half-life enables an extended dosing interval (8 versus 2 weeks). CHAMPION-NMOSD (NCT04201262) is a global, open-label, phase 3 study.

Adult patients received a weight-based intravenous loading dose of ravulizumab, then a maintenance dose on day 15 and every 8 weeks thereafter. Eculizumab availability precluded concurrent placebo control; the PREVENT (NCT01892345) placebo arm was an external comparator. Propensity scores were used to account for potential differences in patient characteristics between arms. Primary endpoint: time to first adjudicated on-trial relapse and relapse risk reduction (RRR). Secondary efficacy endpoints: adjudicated on-trial annualized relapse rate (ARR); clinically important worsening from baseline in Hauser Ambulation Index (HAI) score. 
Median (range) follow-up: 73.5 (11.0, 117.7) weeks for ravulizumab (n=58);  36.0 (1.9, 117.7) weeks for placebo (n=47). The primary endpoint was met; no patients had adjudicated relapses with ravulizumab versus 20 with placebo (RRR, 98.6%; p<0.0001). The ARR (upper 95% CI) was 0.00 (0.04) with ravulizumab: superior to a predefined comparator ARR (0.25; p<0.0001). Fewer patients experienced clinically important HAI score worsening with ravulizumab (2/58; 3.4%) than placebo (11/47; 23.4%; p=0.023); OR, 0.16 (95% CI, 0.03–0.77). Treatment-emergent AEs were reported in 93.1% (ravulizumab) and serious AEs in 13.8%: two vaccinated patients experienced meningococcal infection (2.4/100 patient-years). Both recovered with no sequelae; one continued the trial. No deaths were reported. Despite a longer follow-up (median treatment duration: 90.9 weeks), efficacy and safety data remain consistent with the primary treatment period. No relapses were observed (RRR: 98.7%). 

Ravulizumab significantly lowered risk of relapse and HAI score worsening versus placebo in AQP4+ NMOSD, an effect unaffected by baseline characteristics differences. No changes to the known ravulizumab safety profile were identified.