Across a 58-patient cohort, ravulizumab’s safety and tolerability were consistent with previous clinical studies, with most patients opting to enter a long-term extension period following the study.
AstraZeneca has announced findings from its phase 3 CHAMPION-NMOSD trial (NCT04201262), which showed that ravulizumab-cwvz (Ultomiris) met its primary end point of time to first on-trial relapse, with no relapses observed in 58 patients with anti-aquaporin (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD) over a median treatment duration of 73 weeks.1
Less than 2 weeks after receiving FDA approval to treat generalized myasthenia gravis (gMG), these data on ravulizumab, a long-acting C5 complement inhibitor, show its benefit in adults with anti-AQP4 antibody-positive NMOSD. The therapeutic demonstrated statistically significant and clinically meaningful reductions in the risk of relapse compared with those on placebo from the external PREVENT trial (NCT01892345), a phase 3 study that evaluated eculizumab (Soliris; Alexion), which is FDA-approved for NMOSD treatment.
The company noted that the safety profile of ravulizumab was consistent with what had previously been observed. In total, 56 of the original 58 patient cohort completed the primary treatment period and opted to continue in the long-term extension, which is ongoing.
"Every NMOSD relapse can have debilitating and irreversible consequences, so reducing relapses is critical,” primary investigator Sean J. Pittock, MD, director, Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, said in a statement.1 “Patients on Ultomiris remained relapse free over a median treatment duration of 73 weeks in the trial."
CHAMPION-NMOSD was an open-label, multicenter trial that evaluated the efficacy and safety of ravulizumab in 58 patients with anti-AQP4 NMOSD who had at least 1 attack or relapse in the 12 months prior to the screening visit. These patients also had Expanded Disability Status Scale scores of 7 or less, had body weight of at least 40 kg at trial entry, and were allowed to stay on stable supportive immunosuppressive therapy for the duration of the trial.
On day 1, patients received a single weight-based loading dose of ravulizumab, followed by regular weight-based maintenance dosing beginning on day 15, every 8 weeks. The primary end point, time to first on-trial relapse, could have occurred either when all patients completed or discontinued prior to the week 26 visit and 2 or more adjudicated relapses were observed, or when all patients completed or discontinued prior to the week 50 visit if fewer than 2 adjudicated relapses were observed.
"Soliris established a role of complement inhibition in preventing relapses in NMOSD, and with Ultomiris, we continue to innovate for patients with a more convenient every eight-week dosing schedule,” Marc Dunoyer, chief executive officer, Alexion, said in a statement. "These trial results show that Ultomiris may help patients move towards eliminating relapses, which is an important advancement in the treatment of NMOSD."
The FDA’s decision to approve ravulizumab for patients with gMG who are antiacetylcholine receptor-antibody positive was notable in several ways, as the therapy became the first approved long-acting C5 complement inhibitor for this patient population. The approval was based on data from the phase 3 CHAMPION MG trial (NCT03920293), in which treatment with ravulizumab resulted in rapid and sustained improvement of symptoms in patients with gMG for up to 26 weeks.2
At the end of the treatment period, investigators observed statistically significant improvements on the primary end point of Myasthenia Gravis Activities of Daily Living total score compared with placebo (–3.1 vs –1.4; P <.001).Change in Quantitative Myasthenia Gravis (QMG) total scores, a secondary end point, showed statistically significant improvements following ravulizumab treatment compared with placebo (P <.001). The least squares estimate of the mean QMG change was –2.8 (95% CI, –3.7 to –1.9) in the ravulizumab group and –0.8 (95% CI, –1.7 to 0.1) in the placebo group (P <.001). QMG total scores improved by 5 points or more in a significantly greater proportion of ravulizumab-treated patients than of those receiving placebo (30.0% vs 11.3%; P = .005).3
In 2018, ravulizumab was FDA approved to treat adults with paroxysmal nocturnal hemoglobinuria (PNH) and was later expanded to include children and adolescents in 2021.4 With the expanded indication, it became the first and only approved therapeutic for children and adolescents with PNH.