NEW YORK – AstraZeneca said on Wednesday that it has received a complete response letter from the US Food and Drug Administration regarding its supplemental biologics license application seeking approval for Ultomiris (ravulizumab-cwvz) as a treatment for anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder.
NMOSD patients' immune systems attack healthy tissues and cells in the central nervous system. Three quarters of patients produce antibodies that bind to the aquaporin-4 protein, which aberrantly activates the complement system and hinders the body's ability to fight infection.
Ultomiris is designed to provide sustained inhibition of the C5 protein in the terminal complement cascade. The drug is already approved in the US for treating anti-acetylcholine receptor antibody-positive generalized myasthenia gravis for paroxysmal nocturnal hemoglobinuria or atypical hemolytic uremic syndrome.
In seeking to expand the use of Ultomiris to anti-aquaporin-4 antibody-positive NMOSD, AstraZeneca submitted data from the Phase III CHAMPION-NMOSD trial and compared the outcomes of 58 patients on the investigational treatment to an external placebo arm from the Phase II PREVENT trial of Soliris (eculizumab), another NMOSD treatment sold by AstraZeneca. In the CHAMPION-NMOSD trial, Ultomiris met the primary endpoint of time to first on-trial relapse, with no relapses among patients with a median treatment duration of 73 weeks. Twenty of 47 patients in the external placebo arm reported adjudicated relapses.
According to AstraZeneca, the FDA in its complete response letter did not request additional analysis of the data it submitted in its sBLA from the CHAMPION-NMOSD trial or express concerns about the drug's safety or efficacy. However, the agency did ask the firm to modify Ultomiris' risk evaluation and mitigation strategy (REMS) "to further validate patients' meningococcal vaccination status or prophylactic administration of antibiotics prior to treatment," AstraZeneca said in a statement.
Alexion, the group within AstraZeneca that develops rare disease treatments, is working with the FDA to make the necessary REMS modifications, the firm added.
Regulators in Europe and Japan recently approved Ultomiris for treating anti-aquaporin-4 antibody-positive NMOSD based on the CHAMPION-NMOSD trial data.