FDA Approves Ravulizumab-cwvz for Neuromyelitis Optica Spectrum Disorder

Zero relapses were reported among individuals that received ravulizumab-cwvz over the 73 weeks of treatment.

The FDA has approved ravulizumab-cwvz (Ultomiris, Alexion Pharmaceuticals Inc) for the treatment of adult individuals with anti-aquaporin-4 (AQP4) antibody-positive (Ab+) neuromyelitis optica spectrum disorder (NMOSD). The approval marks ravulizumab-cwvz as the first and only long-acting C5 complement inhibitor that offers relapse-free survival, according to a press release from AstraZeneca.

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NMOSD is a rare disease that is estimated in about 6000 individuals in the United States. The disease occurs when the immune system is wrongly activated to target healthy cells and tissues in the central nervous system, according to the press release. The disease is reported to be most common in women, starting in the mid-30s. While it can impact both men and children, it is more unlikely. However, among individuals impacted with NMOSD, three quarters of individuals generate antibodies that attach to the protein, AQP4— causing them to be anti-AQP4 Ab+. Press release noted that the most common symptoms associated with NMOSD include vision problems, intense pain, loss of bladder/bowel function, abnormal skin sensations, and impact on coordination and/or movement. Most individuals with NMOSD experience relapses that could worsen the neurologic symptoms with each occurrence.

Ravulizumab-cwvz acts by inhibiting the C5 protein in the terminal complement cascade in the body’s immune system, according to the press release. The medication is reported to provide immediate, complete, and sustained complement inhibition.

“C5 inhibition has been proven to offer efficacy in reducing the risk of NMOSD relapses by blocking the complement system, a part of the immune system, from attacking healthy cells in the spinal cord, optic nerve and brain,” said 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, in a press release.

About The CHAMPION-NMOSD Trial

Trial Name: An Efficacy and Safety Study of Ravulizumab in Adult Participants With NMOSD

ClinicalTrials.gov ID: NCT04201262

Sponsor: Alexion Pharmaceuticals Inc

Completion Date (Estimated): July 2024

The approval was based on positive results from the CHAMPION-NMOSD phase 3 trial, an open-label, multicenter study, that compared ravulizumab-cwvz to an external placebo from the eculizumab (Soliris; Alexion Pharmaceuticals) PREVENT clinical trial. The study authors noted that 58 individuals with NMOSD from North America, Europe, Asia-Pacific and Japan were included. The participants were required to have a positive anti-AQP4 antibody test, on attack or relapse 12 months before screening visit, an Expanded Disability Status Scale Score of 7 or less and weigh at least 40 kilograms at the start of the study, according to study authors.

The trial extended a mediation duration of 73 weeks, the study authors said. On day 1, the individuals received a single weight-based dose of ravulizumab-cwvz, continued with a regular weight-based maintenance dose on day 15, every 8 weeks.

The study authors noted that the primary endpoint of time to first on-trial relapse was met, as zero relapses were reported among individuals that received ravulizumab-cwvz, over the 73 weeks of treatment.

“With today’s FDA approval, patients now have the option of a long-acting C5 inhibitor treatment that showed zero relapses in the pivotal CHAMPION-NMOSD trial, supporting the primary goal of relapse prevention in treating NMOSD,” said Pittock, in a press release.

Reference

Ultomiris approved in the US for the treatment of adults with neuromyelitis optica spectrum disorder (NMOSD). AstraZeneca. News release. March 25, 2024. Accessed March 25, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/ultomiris-approved-in-the-us-for-nmosd.html.