PHILADELPHIA – Treatment with the monoclonal antibody eculizumab substantially reduced the risk of relapse versus placebo in patients with aquaporin-4 positive neuromyelitis optica (NMO) spectrum disorder, according to the results of a phase 3 trial reported at the annual meeting of the American Academy of Neurology. Nearly 98% of patients with this autoimmune inflammatory CNS disorder were relapse-free at 48 weeks in the , according to principal investigator , director of the Mayo Clinic’s Center for Multiple Sclerosis and Autoimmune Neurology in Rochester, Minn.
“This was a dramatic result, I think, really showing a significant amount of hope for people with this disease,” Dr. Pittock said in a press conference.
Most cases of NMO are associated with aquaporin-4 antibodies and complement-mediated CNS damage, and eculizumab () is an inhibitor of complement protein C5 shown to reduce relapse frequency in a previous, small open-label study, according to Dr. Pittock.
In the current global phase 3 trial, conducted at 70 centers in 18 countries, 143 adult patients with aquaporin-4 positive NMO spectrum disorder were randomized to eculizumab every 2 weeks or placebo. The trial allowed for supportive immunosuppressive therapy and excluded patients who had received rituximab in the past 3 months. A total of 124 patients completed the study, which was stopped after 23 adjudicated relapses had occurred.
Time to first adjudicated relapse on trial, the primary endpoint of the study, showed a significant effect (P less than .0001) in favor of monoclonal antibody treatment over placebo, with a 94.2% reduction in risk of relapse, according to Dr. Pittock and coinvestigators.
At 48 weeks, 97.9% of patients were relapse free in the eculizumab group, versus 63.2% in the placebo group, they added in their report, which was published May 3 online ahead of print in the New England Journal of Medicine ().
Longer-term follow-up showed that, at 144 weeks, 96% of eculizumab-treated patients remained relapse free, while 45% of the placebo group were relapse free, Dr. Pittock said in the press conference.
Most adverse events seen on treatment were mild to moderate, and no meningococcal infections were observed.
One death occurred in the study from pulmonary empyema in an eculizumab-treated patient, but the associated cultures yielded microorganisms not associated with complement deficiency, investigators said in their published report.
“The concept that you can discover a target, understand the immunopathology of a disease, identify a novel mechanism, then identify a precision drug that targets that mechanism, and essentially turn off, or switch off, the disease is very, very exciting,” Dr. Pittock said in the press conference.
The study was supported by Alexion Pharmaceuticals. Dr. Pittock provided disclosures related to Alexion Pharmaceuticals, MedImmune, and Grifols, along with patents related to administration of eculizumab and cancer markers in neuromyelitis optica.
SOURCE: Pittock SJ et al. AAN 2019, .