Efficacy and Safety of Ravulizumab in Adults With Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (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, Kerstin Allen12, Becky Parks12, Ho Jin Kim13
1Mayo Clinic, 2University of Sydney, 3University of Colorado, 4School of Medicine, Technical University of Munich, 5Strasbourg University Hospital Center, 6Massachusetts General Hospital and 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 (data cutoff: Jun 14, 2024) of ravulizumab in AQP4-Ab+ NMOSD.
Background:
CHAMPION-NMOSD (NCT04201262) is an ongoing global, open-label, phase 3 study evaluating ravulizumab in adults with AQP4-Ab+ NMOSD.
Design/Methods:
Participants 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 (OTR) and relapse risk reduction. Secondary endpoints included adjudicated OTR rate, change from baseline in Hauser Ambulation Index (HAI) and Expanded Disability Status Scale (EDSS) scores, and safety.
Results:
As of 14Jun2024, 58 patients enrolled in the PTP; 56/41 entered/completed the LTE. Median (range) follow-up was 170.3 (11.0-233.9) weeks, with 186.6 patient-years. Across the PTP and LTE, no patients had an adjudicated OTR. 94.8% (55/58 patients) had stable or improved HAI. 89.7% (52/58 patients) had no clinically important worsening in EDSS score. Treatment-emergent adverse event (TEAE) and serious adverse event incidences were 94.8% and 25.9%, respectively. Most TEAEs were mild 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 and none in the extension period. One death (cardiovascular) unrelated to ravulizumab occurred during the LTE.
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 170.3-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-Ab+ NMOSD.
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