Efficacy and Safety of Ravulizumab in Adults With Anti-Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder (AQP4+ NMOSD): Interim Analysis From the Ongoing Phase 3 CHAMPION-NMOSD Trial
Sean Pittock1, Michael Barnett2, Jeffrey Bennett3, Achim Berthele4, Jerome De Seze5, Michael Levy6, Ichiro Nakashima7, Celia Oreja-Guevara8, Jacqueline Palace9, Friedemann Paul10, Carlo Pozzilli11, Yasmin Mashhoon12, Kerstin Allen12, Becky Parks12, Ho Jin Kim13
1Mayo Clinic, 2University of Sydney, 3University of Colorado, 4School of Medicine, Technical University Munich, 5Strasbourg University Hospital Center, 6Massachusetts General Hospital/Harvard Medical School, 7Tohoku Medical and Pharmaceutical University, 8San Carlos Clinical Hospital and Complutense University of Madrid, 9John Radcliffe Hospital, 10Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, 11Sapienza University, 12Alexion, AstraZeneca Rare Disease, 13National Cancer Center
Objective:
To report the interim efficacy and safety of ravulizumab in AQP4+ NMOSD.
Background:
CHAMPION-NMOSD (NCT04201262) is an ongoing global, open-label, phase 3 study evaluating ravulizumab in AQP4+ NMOSD.
Design/Methods:
Adult patients received an intravenous, weight-based loading dose of ravulizumab on day 1 and a maintenance dose on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). PTP primary endpoints were time to first adjudicated on-trial relapse and relapse risk reduction. Secondary endpoints included adjudicated on-trial relapse rate, change from baseline in Hauser Ambulation Index (HAI) and Expanded Disability Status Scale (EDSS) scores, and safety.
Results:
58 patients enrolled in the PTP; 56/2 entered/completed the LTE. As of 16Jun2023, median (range) follow-up was 138.4 (11.0-183.1) weeks for ravulizumab (n=58), with 153.9 patient-years. Across the PTP and LTE, no patients had an adjudicated on-trial relapse during ravulizumab treatment. 91.4% (53/58 patients) had stable or improved HAI score. 91.4% (53/58 patients) had no clinically important worsening in EDSS score. Treatment-emergent adverse event (TEAEs) and serious adverse event incidences were 94.8% and 25.9%, respectively. Most TEAEs were mild to moderate in severity and unrelated to ravulizumab. TEAEs leading to withdrawal from study drug occurred in 1 patient. Two cases of meningococcal infection occurred during the PTP, none in the extension period. One death occurred (cardiovascular) during the LTE and was unrelated to ravulizumab.
Conclusions:
Consistent with outcomes during the PTP, no patients treated with ravulizumab experienced an adjudicated relapse and most demonstrated stable or improved disability measures through the longer-term 138.4-week median follow-up. The safety profile is consistent with prior analyses, and notably no new meningococcal infections beyond the 2 during the PTP were observed. Together, these findings demonstrate the long-term clinical benefit of ravulizumab in the prevention of relapses in AQP4+ NMOSD.