Ultomiris in NMOSD: Transformative Insights from ECTRIMS 2025

At the 2025 ECTRIMS Congress in Barcelona, final long-term data from the CHAMPION-NMOSD Phase III trial are drawing considerable attention—not just for their scientific rigor, but for what they may signal: a fundamental shift in the treatment landscape for neuromyelitis optica spectrum disorder (NMOSD). The headline finding: zero adjudicated relapses among patients treated with Ultomiris (ravulizumab) through a median follow-up of more than three years.

These results have earned a place among the ‘Best of ECTRIMS 2025,’ and for good reason. NMOSD is a rare, relapsing autoimmune disorder of the central nervous system characterized by unpredictable attacks that often lead to cumulative and irreversible disability. The trial’s principal investigator, Dr. Sean Pittock of the Mayo Clinic, underscored the magnitude of the findings: “Every relapse in NMOSD carries a real risk of permanent neurological damage. To see no relapses over this extended timeframe is extraordinary.”

Ultomiris, a long-acting complement C5 inhibitor developed by Alexion, AstraZeneca Rare Disease, appears to have achieved what was once considered aspirational—durable, sustained remission. The final results from the trial’s long-term extension (LTE), encompassing 170.3 weeks of follow-up, showed a 98.9% risk reduction in relapses (P < 0.0001). Importantly, 81% of patients maintained clinical stability, and 13.8% improved based on Hauser Ambulation Index scores. Disability worsening, as measured by the EDSS, was largely absent in over 90% of patients.

Equally telling is what happened to patients' concomitant therapies. Nearly two-thirds of those who entered the trial on immunosuppressive therapy either reduced their dose or discontinued at least one agent altogether. That shift, along with the durable control observed, suggests Ultomiris may enable a simplified, more tolerable long-term regimen for many patients.

Beyond the pivotal trial data, Alexion also presented a wealth of real-world evidence reinforcing the clinical relevance of C5 inhibition in NMOSD. Findings from the NMO SPOTLIGHT Registry—encompassing 56 patients treated with either Ultomiris or its predecessor, Soliris (eculizumab)—showed a dramatic drop in annualized relapse rate from 0.50 to 0.02 after initiating treatment. Notably, no patients experienced more than one relapse, and among those who had switched from rituximab, none relapsed during follow-up.

In Japan, early results from a study evaluating Ultomiris in patients with suboptimal response to satralizumab revealed similar promise. After a mean of nearly 11 months on treatment, 10 out of 11 patients remained relapse-free. Concomitant immunosuppressive use declined across the board, and biomarker shifts—such as reductions in pathogenic B cell subsets—hinted at deeper immunological changes that may help explain the observed stability.

These developments arrive at a time when neurologists are increasingly being asked to navigate complex treatment decisions in NMOSD, balancing efficacy, safety, and quality of life considerations. While multiple targeted therapies are now approved for AQP4-Ab+ NMOSD—including eculizumab, satralizumab, and inebilizumab—the long-term comparative durability of effect remains a pressing clinical question.

Ravulizumab’s advantage lies in both its pharmacology and its clinical performance. With dosing intervals every eight weeks—compared to biweekly for eculizumab—it offers meaningful convenience without compromising potency. That distinction, when paired with the CHAMPION trial’s long-term findings, may push clinicians to re-evaluate existing treatment hierarchies.

Meanwhile, new data from the ongoing AMAZE study, which investigates not just the biological effects of Ultomiris but also the social determinants of health in NMOSD care, hint at an even broader vision. In a disease where timely diagnosis and equitable access to care often lag, particularly across underrepresented populations, these insights may prove just as critical as pharmacological breakthroughs.

As Alexion deepens its investment in complement biology and expands its rare neurology portfolio, Ultomiris is shaping up to be more than a next-generation treatment—it’s positioning itself as a long-term anchor in the management of a once-devastating disease. For clinicians and patients alike, the message from ECTRIMS 2025 is clear: durable remission in NMOSD is no longer an elusive goal—it’s an achievable outcome.