2026 American Academy of Neurology Abstract Website

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, Becky Parks¹², Ho Jin Kim¹³
¹Mayo Clinic, ²University of Sydney, ³University of Colorado, Anschutz Medical Campus, ⁴School of Medicine and Health, Technical University of Munich, ⁵University Hospital of Strasbourg, ⁶Massachusetts General Hospital and Harvard Medical School, ⁷Tohoku Medical and Pharmaceutical University, ⁸San Carlos Clinical Hospital and Complutense University of Madrid, ⁹John Radcliff Hospital, ¹⁰Charité-Universitätsmedizin Berlin and Max Delbrück Centre for Molecular Medicine, ¹¹Sapienza University, ¹²Alexion, AstraZeneca Rare Disease, ¹³National Cancer Center

Objective:

To report end-of-study efficacy and safety results from CHAMPION-NMOSD (NCT04201262), a phase 3, open-label, external placebo-controlled trial evaluating ravulizumab in AQP4-Ab+ NMOSD.

Background:

Ravulizumab, a complement component 5 inhibitor, is approved for adults with AQP4-Ab+ NMOSD.

Design/Methods:

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 the primary treatment period (PTP; up to 2.5 years), patients could enter the long-term extension (LTE). The primary endpoint was time to first adjudicated on-trial relapse (OTR) and associated relapse risk reduction. Secondary endpoints included change from PTP baseline in Hauser Ambulation Index (HAI) and Expanded Disability Status Scale (EDSS) scores and safety.

Results:

Of 58 patients enrolled, 56 entered and 55 completed the LTE. Median (range) follow-up was 170.3 (11.0-243.0) weeks (189.7 patient-years). No patient receiving ravulizumab had an adjudicated OTR throughout the trial; relapse risk reduction vs placebo was 98.9% (95% CI, 91.8-100; P<0.0001). HAI scores remained stable (47/58 [81.0%]) or improved (8/58 [13.8%]) from baseline for most patients, and 91.4% (53/58 patients) had no clinically important worsening on EDSS. Of 27 patients taking immunosuppressive therapy (IST) at baseline, 17 (63.0%) reduced dose or discontinued ≥1 IST. Treatment-emergent adverse events (TEAEs) and serious TEAEs occurred in 94.8% and 27.6% of patients, respectively. For most patients, TEAEs were grade 1 (86.2%) and unrelated to ravulizumab (94.8%). One patient withdrew due to TEAEs. Two cases of meningococcal infection occurred during the PTP and none in LTE. One death (cardiovascular) unrelated to ravulizumab occurred during the LTE.

Conclusions:

No patient receiving ravulizumab in CHAMPION-NMOSD had an adjudicated relapse, and most demonstrated stable/improved disability. The safety profile is consistent with prior analyses. No meningococcal infections occurred during the LTE. These findings demonstrate the long-term clinical benefit of ravulizumab in adult patients with AQP4-Ab+ NMOSD.