2023 American Academy of Neurology Abstract Website

Michael Levy¹, Sean Pittock², Michael Barnett³, Jeffrey Bennett⁴, Achim Berthele⁵, Jerome De Seze⁶, Ichiro Nakashima⁷, Celia Oreja Guevara⁸, Jacqueline Palace⁹, Friedemann Paul¹⁰, Carlo Pozzilli¹¹, Kerstin Allen¹², Yasmin Mashhoon¹², Marcus Yountz¹³, Ho Jin Kim¹⁴
¹Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA, ²Department of Neurology, Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USA, ³Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia; Department of Neurology, Royal Prince Alfred Hospital, Sydney, NSW, Australia, ⁴Departments of Neurology and Ophthalmology, Programs in Neuroscience and Immunology, University of Colorado, Aurora, CO, USA, ⁵Department of Neurology, School of Medicine, Technical University of Munich, Munich, Germany, ⁶Department of Neurology and Clinical Investigation Center, CHU de Strasbourg, France, 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

Objective:

This prespecified analysis of the CHAMPION-NMOSD global, open-label, multicenter, phase 3, externally controlled study aimed to evaluate the efficacy of ravulizumab in clinically relevant patient subgroups.

Background:

CHAMPION-NMOSD (NCT04201262) is a study of ravulizumab in adults with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder. Ravulizumab binds to the same complement component 5 epitope as eculizumab; however, its longer elimination half-life extends the dosing interval (every 8 versus 2 weeks).

Design/Methods:

Patients (≥18 years) received a weight-based intravenous loading dose of ravulizumab (2400–3000 mg) on day 1, followed by maintenance doses (3000–3600 mg) on day 15 and once every 8 weeks thereafter. Concurrent placebo treatment was precluded owing to the availability of eculizumab and other treatments; the placebo arm from PREVENT (NCT01892345) was the external comparator. Prespecified efficacy subgroup analyses of time to first adjudicated on-trial relapse (primary endpoint) were conducted and safety outcomes were analyzed across subgroups.

Results:

At baseline, 30/58 ravulizumab-treated patients were receiving monotherapy and 28/58 concomitant immunosuppressive therapy (IST): steroids (n=12), azathioprine (n=7), mycophenolate mofetil (n=6) or other (n=3). No ravulizumab-treated patient experienced a positively adjudicated on-trial relapse. Based on time to first adjudicated on-trial relapse, ravulizumab was superior to placebo in preventing on-trial relapse in monotherapy (HR, 0.021; 95% CI: 0–0.176; relapse risk reduction [RRR], 97.9%; p<0.0001) and IST groups (HR, 0.031; 95% CI: 0–0.234; RRR, 96.9%; p<0.0001). Significant differences versus placebo were seen in patients who had previously received rituximab (n=20; RRR, 93.7%; p=0.0078) or not (n=38; RRR, 98.1%; p<0.0001). Ravulizumab was superior to placebo in prespecified subgroups by age, sex, race and geographic region. Overall safety profile was consistent with that of ravulizumab across other approved indications.

Conclusions:

The robust effect of ravulizumab on RRR was observed across all prespecified subgroups, including ravulizumab monotherapy, concomitant IST use, age, sex, geographic region, and prior rituximab use.