The First Long-Acting C5 Complement Inhibitor Treatment for Adults with AQP4+ NMOSD Approved

The Food and Drug Administration (FDA) has approved Ultomiris (ravulizumab-cwvz; Alexion, Boston, MA) for the treatment of adults with anti-aquaporin-4 antibody positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD). Ultomiris is the first and only long-acting C5 complement inhibitor approved for this population and is administered intravenously once every 8 weeks after an initial loading dose. As a treatment for NMOSD, Ultomiris functions by inhibiting the C5 protein’s role in the terminal complement cascade, which is involved in the pathologic mechanisms underlying the disorder.

Ultomiris’s approval for NMOSD is based on positive data from the CHAMPION-NMOSD (NCT04201262) clinical trial, which were presented at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and published in Annals of Neurology. CHAMPION-NMOSD was a phase 3, open-label, externally controlled interventional study evaluating the safety and efficacy of Ultomiris as a treatment for adults with AQP4+ NMOSD. A total of 58 participants aged ≥18 years with a diagnosis of AQP4+ NMOSD were included in the study and treated with Ultomiris. The primary efficacy endpoint was time to first adjudicated on-trial relapse and associated relapse risk reductions. Results were compared with participants in the placebo group (n=47) of the phase 3 PREVENT clinical trial (NCT01892345), which assessed the safety and efficacy of eculizumab for people with AQP4+ NMOSD.

In CHAMPION-NMOSD, Ultomiris met the primary endpoint. At 73.5 weeks of follow-up, none of the participants who received Ultomiris experienced a relapse as confirmed by an independent adjudication committee. In comparison, 20 participants in the PREVENT placebo group experienced an adjudicated relapse (relapse risk reduction, 98.6%; hazard ratio (HR), .014; 95% CI, .000 to .103; P<.0001). Additionally, Ultomiris showed a safety and tolerability profile consistent with previous clinical trials and real-world use with no new safety signals.

“With today’s FDA approval, patients now have the option of a long-acting C5 inhibitor treatment that showed zero relapses in the pivotal CHAMPION-NMOSD trial, supporting the primary goal of relapse prevention in treating NMOSD,” said Sean J. Pittock, MD, Lead Primary Investigator for CHAMPION-NMOSD and Director of the Mayo Clinic’s Center for Multiple Sclerosis and Autoimmune Neurology.

Ultomiris’s label contains a boxed warning for serious meningococcal infections.