Ravulizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder.
Pittock SJ., Barnett M., Bennett JL., Berthele A., de Seze J., Levy M., Nakashima I., Oreja-Guevara C., Palace J., Paul F., Pozzilli C., Yountz M., Allen K., Mashhoon Y., Kim HJ.
OBJECTIVE: CHAMPION-NMOSD (NCT04201262) is a phase 3, open-label, externally controlled interventional study evaluating the efficacy and safety of the terminal complement inhibitor ravulizumab in adult patients with anti-aquaporin-4 antibody-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD). Ravulizumab binds the same complement component 5 epitope as the approved therapeutic eculizumab but has a longer half-life, enabling an extended dosing interval (8 versus 2 weeks). METHODS: The availability of eculizumab precluded the use of a concurrent placebo control in CHAMPION-NMOSD; consequently, the placebo group of the eculizumab phase 3 trial PREVENT (n = 47) was used as an external comparator. Patients received weight-based intravenous ravulizumab on day 1 and maintenance doses on day 15, then once every 8 weeks. The primary endpoint was time to first adjudicated on-trial relapse. RESULTS: The primary endpoint was met; no patients taking ravulizumab (n = 58) had an adjudicated relapse (during 84.0 patient-years of treatment) versus 20 patients with adjudicated relapses in the placebo group of PREVENT (during 46.9 patient-years; relapse risk reduction, 98.6% [95% confidence interval, 89.7% to 100.0%], p