Abstract Details

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).

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.

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.

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.

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.