FDA Approves Ultomiris for Neuromyelitis Optica Spectrum Disorder

The Food and Drug Administration (FDA) has approved Ultomiris^® (ravulizumab-cwvz) for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive.

Ultomiris is a long-acting C5 complement inhibitor that is also indicated for the treatment of generalized myasthenia gravis, paroxysmal nocturnal hemoglobinuria, and atypical hemolytic uremic syndrome. The approval of the NMOSD indication was based on data from phase 3 CHAMPION-NMOSD trial (ClinicalTrials.gov Identifier: NCT04201262).

The open-label, external placebo-controlled trial evaluated the efficacy and safety of Ultomiris in 58 adults with anti-AQP4 antibody positive NMOSD. Patients were administered Ultomoris intravenously according to weight-based recommended dosage.

Due to the potential long-term functional impact of NMOSD relapses, Ultomiris was compared with the external placebo arm from the phase 3 Soliris^® PREVENT trial (ClinicalTrials.gov Identifier: NCT01892345). The primary endpoint was time to first adjudicated on-trial relapse, as confirmed by an independent adjudication committee.

Findings showed treatment with Ultomiris resulted in a statistically significant and clinically meaningful reduction in the risk of relapse compared with the external placebo arm. Over a median treatment duration of 73 weeks, there were no relapses observed among patients treated with Ultomiris. The hazard ratio for Ultomiris compared with placebo was 0.014 ([95% CI, 0.000-0.103]; P <.0001), representing a 98.6% reduction in the risk of relapse.

“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. “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.”

The most common adverse reactions reported with Ultomiris in patients with NMOSD included COVID-19, headache, back pain, arthralgia, and urinary tract infection. The prescribing information for Ultomiris includes a Boxed Warning regarding the risk of serious meningococcal infections that have developed in patients who have received treatment. Because of this risk, Ultomiris is only available through a restricted program called the Ultomiris and Soliris REMS.