BARCELONA, Spain — Use of ravulizumab for long-term treatment of neuromyelitis optica spectrum disorder (NMOSD) offered sustained protection from relapse for at least 3 years, results from the CHAMPION-NMOSD open-label extension trial showed.

All patients in the trial were relapse-free over a medium follow-up of 170.3 weeks that includes both the primary treatment period and the long-term extension.

More than 90% showed no clinical worsening during that time with no new safety concerns, reported lead investigator Sean J. Pittock, MD, director of the Center for Multiple Sclerosis and Autoimmune Neurology at the Mayo Clinic, Rochester, Minnesota.

The findings were presented on September 26 at the Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2025.

Second-Generation Results

Razulizumab is a second-generation complement inhibitor that was approved in the US in 2024 for adults with anti-aquaporin-4 antibody-positive (AQP4-Ab+) NMOSD. It works similar to the first complement inhibitor approved for the disorder, eculizumab, which was cleared by the FDA in 2019.

Both drugs are based on C5 epitope binding, but ravulizumab has a configuration that provides a substantially longer elimination half-life. This allows for an extended dosing interval of every 8 weeks compared to dosing every 2 weeks with eculizumab.

For the open-label extension of CHAMPION-NMOSD, 58 patients with confirmed AQP4-Ab+ NMOSD received a weight-based infusion of ravulizumab on days 1 and 15 and then every 8 weeks.

The use of a placebo control arm for CHAMPION had been rendered unethical due to the availability of eculizumab. So researchers used the placebo group (n = 47) of the eculizumab pivotal phase 3 PREVENT trial as the control for the CHAMPION study.

Despite the absence of relapses on ravulizumab over the median primary follow-up of 73.5 weeks, the relapse risk reduction was calculated to be 98.6% (P < .0001) with a tight 95% CI (89.7%-100%).

Yet the absence of relapse was not fully protective against clinical worsening. Five patients (8.6%) in the extension study worsened on either the Expanded Disability Status Scale or the Hauser Ambulation Index. Only one patient worsened on both.

Of those without clinical worsening, 37 (63.8%) were clinically stable, and 16 (27.6%) improved from baseline to the end of follow-up, Pittock reported.

No New Safety Signals

While there were two meningococcal infections in the CHAMPION-NMOSD primary treatment period, there were no further infections in the long-term follow-up.

Overall, there were no safety signals in the extended follow-up relative to the primary treatment period.

Of infections observed in more than 10% of patients, COVID-19 (48.3%) was the most common followed by urinary tract infection (17.2%) and upper respiratory tract infections (15.5%).

Only three patients (1.7%) discontinued therapy on the basis of a treatment-emergent side effect.

Outside of infection, headache (32.8%) was the most common adverse event. Numerous nonspecific complaints, such as back pain and diarrhea, occurred at relatively low rates (< 15%) with an uncertain relevance to treatment.

Ravulizumab vs Eculizumab

Although there has been no head-to-head comparison between the first- and second-generation complement inhibitors, there are similarities and differences worth highlighting, noted Pittock, who led the PREVENT study of eculizumab and the CHAMPION-NMOSD primary and extension trials of ravulizumab.

Immunosuppressive therapy (IST), including corticosteroids, azathioprine, and mycophenolate mofetil, were permitted in both CHAMPION-NMOSD and PREVENT studies. In PREVENT study, approximately 75% were on an IST at enrollment vs only 46.6% of those in CHAMPION-NMOSD.

In the PREVENT trial, most patients treated with eculizumab with or without adjunctive IST achieved stable disease or clinical improvement that extended until the end of the study period. In an analysis limited to those who were treated with eculizumab monotherapy, which was published in 2022, disease control was at least as good for those receiving no IST.

Eculizumab was also associated with a very high protection against relapses. However, with 3 relapses in 96 (3%) patients, complete freedom from relapse was not achieved, Pittock noted.

Of patients who entered the PREVENT open-label extension study on IST, 22.7% decreased their use and 14.3% discontinued the use. In CHAMPION-NMOSD study, the figures were 29.6% and 33.3%, respectively.

According to historic data cited by Pittock, the NMOSD prognosis was extremely poor before the introduction of any IST. In these patients, the 5-year mortality was approximately 50% with most survivors developing major complications including blindness. ISTs prolonged survival, but the extended results with eculizumab and ravulizumab represent a major advance, Pittock reported.

There are other therapeutic options in development for NMOSD, but complement inhibitors have provided the lowest annualized relapse rate (ARR) so far. Relative to the rituximab ARR of 0.17, eg, the rates of 0.02 and 0.0 for eculizumab and ravulizumab, respectively, represent about a 10-fold reduction in risk, according to a review article that was published this year.

However, the lead author of that article, Stanislas Demuth, MD, PhD, neurologist associated with the University Hospital of Strasbourg, Strasbourg, France, agreed that the relative efficacy and safety of eculizumab and ravulizumab remain unknown without a direct comparison, and costs might be a factor in selecting between the two.

But he did suggest that ravulizumab has an important practical advantage.

“The longer half-life allows infusions to be every 8 weeks, which decreases the treatment burden for patients,” he reported, noting that the short dosing interval has been an obstacle to treatment with eculizumab for some patients.

This study was funded by Alexion and AstraZeneca. Pittock reported having financial relationships with Alexion, Adimmune, Amgen, Arialys, Astellas, Hoffman-LaRoche, and Genentech, Sage Therapeutics, and UCB. Demuth reported having no potential conflicts of interest.