Eculizumab (Soliris), a first-in-class complement inhibitor, is now approved for aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD) following an expedited 6-month priority review.
Developed by Alexion Pharmaceuticals, the monoclonal antibody is designed to inhibit specific proteins in the complement system that are activated by anti-AQP4 antibodies. Results from the deciding phase 3 trial showed that eculizumab reduces the risk of relapse and prolongs the time to first adjudicated relapse.
“This is the first treatment that has been FDA approved for this debilitating condition,” said John Chen, MD, PhD, a neuro-ophthalmologist at Mayo Clinic who was not involved in the trial. “Rituximab and other non-FDA approved traditional medications for NMOSD are often effective, but it is good to know that we have an ace up our sleeves if a patient has severe relapses despite these medications.”
The agency approved the drug based on positive safety and efficacy outcomes from the randomized double-masked controlled PREVENT trial. Published in the May 2019 issue of the New England Journal of Medicine, the findings showed that 96% of the treatment group remained relapse free at 144 weeks, compared with 45% in the placebo group.
The most common adverse event was upper respiratory tract infection and the most serious were pneumonia, cellulitis, sepsis and urinary tract infection. One eculizumab-treated patient died from infectious plural effusion.
Despite the encouraging outcomes from the trial, Dr. Chen notes there is still insufficient data to suggest the therapy will be effective for patients with seronegative NMOSD or those with NMOSD-like phenotype who are myelin oligodendrocyte glycoprotein (MOG)-IgG positive. In addition, he says, many patients in the trial were treated with an adjunct immunosuppressive therapy, and its efficacy as a monotherapy has not been fully established.
The latest FDA approval adds to eculizumab’s indications, which already include adult paroxysmal nocturnal hemoglobinuria and pediatric atypical hemolytic uremic syndrome. The EU and Japan are in the process of reviewing Alexion’s application to add NMOSD to the drug’s marketing authorization.
“The FDA approval will make it easier for insurance companies to cover the costs of this efficacious treatment,” said Dr. Chen. “With other randomized trials for NMOSD currently showing promising results, it will likely be a matter of time before we have other treatments that are FDA approved.”