Ultomiris from AstraZeneca showed zero relapses in adults with neuromyelitis optica spectrum disorder (NMOSD) with median treatment duration of 73 weeks.

Data were presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress.

Sean J. Pittock, MD, Director of Mayo Clinic's Center for Multiple Sclerosis and Autoimmune Neurology and of Mayo's Neuroimmunology Laboratory and lead primary investigator in the CHAMPION-NMOSD trial, said: “The CHAMPION-NMOSD trial showed zero relapses with a median treatment duration of 73 weeks, providing evidence that ravulizumab may offer patients sustained reduction in the risk of relapse with dosing every eight weeks and underscoring the efficacy of C5 inhibition in managing NMOSD.”.

Michael Yeaman, PhD, Professor of Medicine at the UCLA School of Medicine, Director of the Institute for Infection and Immunity, Lundquist Institute at Harbor–UCLA and Chair Medical Advisor to the Guthy-Jackson Charitable Foundation for NMOSD, said: “In recent years, we have seen meaningful progress in bringing safe and effective treatments to patients with AQP4 Ab+ NMOSD, a rare disease that can disrupt many aspects of daily life, including mobility, vision, strength and balance. Based on insights from working with patients and their families every day, continued innovative research and clinical trials help empower people living with NMOSD by advancing new treatment options that may be more compatible with their individual needs and lifestyles.”

NMOSD is a rare and debilitating autoimmune disease that affects the central nervous system (CNS), including the spine and optic nerves. Most people living with NMOSD experience unpredictable relapses, characterised by a new onset of neurologic symptoms or worsening of existing neurologic symptoms, which tend to be severe and recurrent and may result in permanent disability.

CHAMPION-NMOSD is a global Phase III, open-label, multicentre trial evaluating the safety and efficacy of Ultomiris in adults (n=58). Due to the potential long-term functional impact of NMOSD relapses and available effective treatment options, a direct placebo comparator arm was precluded for ethical reasons. Ultomiris, the active treatment, was compared to the external placebo arm from the pivotal Soliris PREVENT clinical trial. Data showed zero adjudicated relapses were observed among Ultomiris patients with a median treatment duration of 73 weeks (relapse risk reduction: 98.6%, hazard ratio (95% CI): 0.014 (0.000, 0.103), p<0.0001). additionally, 100% of patients receiving ultomiris remained relapse-free at 48 weeks, compared to 63% of patients in the external placebo arm.></0.0001).>

The CHAMPION-NMOSD trial also met key secondary efficacy endpoints , including adjudicated on-trial annualised relapse rate (total number of relapses in the study divided by total number of patient years) and clinically important change from baseline in mobility (ability to walk) as measured by Hauser Ambulation Index (a scale to assess mobility).

Overall, the safety and tolerability of Ultomiris was consistent with previous clinical studies and real-world use and no new safety signals were observed. The most common adverse events (AEs) (greater than or equal to 10% of patients) were COVID-19 (24%), headache (24%), back pain (12%), arthralgia (10%) and urinary tract infection (10%). All cases of COVID-19 were non-serious and considered to be unrelated to Ultomiris. There were two meningococcal infections reported; both patients recovered fully with no sequelae and one continued in the trial. Fifty-six patients are continuing to receive treatment in an ongoing long-term extension period.

CHAMPION-NMOSD subgroup and sensitivity analyses : Additional results from the CHAMPION-NMOSD trial were also presented at ECTRIMS in two posters, detailing subgroup and sensitivity analyses. In the subgroup analysis, based on time to first adjudicated on-trial relapse, Ultomiris was superior to the external placebo arm in patients receiving monotherapy (n=30; hazard ratio [HR]: 0.021; 95% confidence interval [CI]: 0.000–0.176; relapse risk reduction [RRR]: 97.9%; p<0.0001) and in patients receiving concomitant therapy (n="28;" hr: 0.031; 95% ci: 0.000–0.234; rrr: 96.9%; p><0.0001). significant differences were observed in patients who had received rituximab in the previous year (n="20;" hr: 0.063; 95% ci: 0.000–0.562; rrr: 93.7%; p="0.0078)" or had not (n="38;" hr: 0.019; 95% ci: 0.000-0.142; rrr 98.1%; p><0.0001) compared to placebo. the robust treatment effect of ultomiris was also observed across pre-specified efficacy subgroups, including age (><45 years or ?45 years: rrr: 95.7–97.9%; p?0.0012), sex (rrr: 94.3–98.2%; p?0.0068), asian and white races (rrr: 95.1–97.8%; p?0.0027) and geographic region (rrr: 91.5–96.1%; p?0.025).></45></0.0001)></0.0001).></0.0001)>

Further, pre-specified sensitivity analyses were conducted to account for potential differences in baseline patient characteristics that could impact treatment efficacy. Time to first adjudicated relapse and relapse risk reduction were analysed using a stabilised inverse probability of treatment weighting approach. The results were consistent with the primary analysis, suggesting that any differences in baseline characteristics between the Ultomiris and external placebo groups did not impact the treatment effect.

Regulatory submissions for Ultomiris for the treatment of NMOSD are currently under review with multiple health authorities, including in the United States (US), European Union (EU) and Japan.