Ultomiris Data Shows No Relapses in Adults with NMOSD with Median Treatment Duration of 73 Weeks
October 27, 2022
AstraZeneca’s Alexion Rare Diseases reported that detailed positive results from the phase 3 CHAMPION-NMOSD trial showed that Ultomiris significantly reduced relapse risk in adults with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder compared to the external placebo arm from the pivotal Soliris PREVENT clinical trial.
Data were presented today at the European Committee for Treatment and Research in Multiple Sclerosis Congress.
Neuromyelitis optica spectrum disorder (NMOSD) is a rare disease in which the immune system is inappropriately activated to target healthy tissues and cells in the central nervous system. Approximately three-quarters of people with NMOSD are anti-AQP4 Ab+, meaning they produce antibodies that bind to a specific protein, aquaporin-4 (AQP4). 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. Most people living with NMOSD experience unpredictable relapses, characterized 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. NMOSD is a distinct disease from other CNS diseases, including multiple sclerosis. The journey to diagnosis can be long, with the disease sometimes misdiagnosed.
Ultomiris (ravulizumab-cwvz), the first and only long-acting C5 complement inhibitor, provides immediate, complete and sustained complement inhibition. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. Ultomiris is administered intravenously every eight weeks in adult patients, following a loading dose.
“The CHAMPION-NMOSD trial showed zero relapses with a median treatment duration of 73 weeks, providing evidence that ravulizumab-cwvz 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,” said Sean Pittock, 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.
CHAMPION-NMOSD is a global phase 3, open-label, multicenter trial evaluating the safety and efficacy of Ultomiris in adults. 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 with a relapse risk reduction of 98.6 percent. Additionally, 100 percent of patients receiving Ultomiris remained relapse-free at 48 weeks, compared to 63 percent of patients in the external placebo arm.
The CHAMPION-NMOSD trial also met key secondary efficacy endpoints, including adjudicated on-trial annualized 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 (greater than or equal to 10 percent of patients) were COVID-19, headache, back pain, arthralgia, and urinary tract infection. 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.
Regulatory submissions for Ultomiris for the treatment of NMOSD are currently under review with multiple health authorities, including in the United States, European Union, and Japan.
Ultomiris is approved in the United States, European Union, and Japan for the treatment of certain adults with generalized myasthenia gravis, for the treatment of certain adults and children with paroxysmal nocturnal hemoglobinuria, and for certain adults and children with atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy.
Author: Rare Daily Staff
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