10 May 2022 - - Positive high-level results from the open-label Phase III CHAMPION-NMOSD trial showed that Ultomiris (ravulizumab-cwvz) achieved a statistically significant and clinically meaningful reduction in the risk of relapse in adults with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (NMOSD) compared to the external placebo arm from the pivotal SOLIRIS PREVENT clinical trial, UK-based pharmaceutical company AstraZeneca's (NYSE: AZN) Alexion rare disease business said.

Ultomiris, the first and only long-acting C5 complement inhibitor, met the primary endpoint of time to first on-trial relapse, as confirmed by an independent adjudication committee.

Notably, no relapse was observed in 58 patients over a median treatment duration of 73 weeks.

NMOSD is a rare and devastating autoimmune disease that affects the central nervous system, including the spine and optic nerves.

Most people living with NMOSD often experience unpredictable relapses, a new onset of neurologic symptoms or worsening of existing neurologic symptoms, also referred to as attacks, which tend to be severe and recurrent and may result in permanent disability.

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: "Every NMOSD relapse can have debilitating and irreversible consequences, so reducing relapses is critical. Patients on Ultomiris remained relapse free over a median treatment duration of 73 weeks in the trial."

The safety and tolerability of Ultomiris in the Champion-NMOSD trial were consistent with previous clinical studies and other approved indications. Fifty-six patients are continuing to receive treatment in a long-term extension period, which is ongoing.

The data will be presented at a forthcoming medical meeting and submitted to global health authorities as rapidly as possible to bring forward Ultomiris to the NMOSD community.

NMOSD is a rare disease in which the immune system is inappropriately activated to target healthy tissues and cells in the CNS.

Approximately three-quarters of people with NMOSD are anti-AQP4 Ab+, meaning they produce antibodies that bind to a specific protein, aquaporin-4.

This binding can inappropriately activate the complement system, which is part of the immune system and is essential to the body's defense against infection, to destroy cells in the optic nerve, spinal cord and brain.

It most commonly affects women and begins in the mid-30s. Men and children may also develop NMOSD, but it is even more rare.

People with NMOSD may experience vision problems, intense pain, loss of bladder/bowel function, abnormal skin sensations (eg, tingling, prickling or sensitivity to heat/cold) and impact on coordination and/or movement.

Most people living with NMOSD experience unpredictable relapses, also known as attacks. Each relapse can result in cumulative disability including vision loss, paralysis and sometimes premature death.

NMOSD is a distinct disease from other CNS diseases, including multiple sclerosis. The journey to diagnosis can be long, with the disease sometimes misdiagnosed.

CHAMPION-NMOSD is a global Phase III, open-label, multicenter trial evaluating the safety and efficacy of ULTOMIRIS in adults with NMOSD.

The trial enrolled 58 patients across North America, Europe, Asia-Pacific and Japan. Participants were required to have a confirmed NMOSD diagnosis with a positive anti-AQP4 antibody test, at least one attack or relapse in the twelve months prior to the screening visit, an Expanded Disability Status Scale Score of 7 or less and body weight of at least 40 kilograms at trial entry.

Participants could stay on stable supportive immunosuppressive therapy for the duration of the trial.

Due to the potential long-term functional impact of NMOSD relapses, a direct placebo comparator arm was precluded for ethical reasons. The active treatment was compared to an external placebo arm from the pivotal SOLIRIS PREVENT clinical trial.

Over a median treatment duration of 73 weeks, all enrolled patients received a single weight-based loading dose of ULTOMIRIS on Day 1, followed by regular weight-based maintenance dosing beginning on Day 15, every eight weeks.

The primary endpoint was time to first on-trial relapse, as confirmed by an independent adjudication committee.

The end of the primary treatment period could have occurred either when all patients completed or discontinued prior to the Week 26 visit and two or more adjudicated relapses were observed, or when all patients completed or discontinued prior to the Week 50 visit if fewer than two adjudicated relapses were observed.

In the trial, there were zero adjudicated relapses so the end of the primary treatment period occurred when the last enrolled participant completed the 50 week visit.

Alexion, AstraZeneca Rare Disease, is the group within AstraZeneca focused on rare diseases, created following the 2021 acquisition of Alexion Pharmaceuticals, Inc. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in more than 50 countries.