First Clinical Trial in MOGAD Meets Primary Endpoint

The interleukin-6 (IL-6) inhibitor satralizumab (Enspryng) met its primary endpoint in the phase III METEOROID trial of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

Satralizumab reduced the risk of a new relapse by 68% compared with placebo (HR 0.32, 95% CI 0.15-0.70, P=0.0025) in adults and adolescents with MOGAD, reported Michael Levy, MD, PhD, of Massachusetts General Hospital and Harvard Medical School in Boston, at the American Academy of Neurology annual meeting.

At week 48, 87.3% of MOGAD patients who received satralizumab remained relapse-free, compared with 66.5% of patients in the placebo group. Clinical benefits were observed as early as week 8. The treatment effect was broadly consistent across subgroups, including differences in age, sex, race, and use of background immunosuppressive therapies.

“METEOROID represents the first prospective randomized controlled study in MOGAD and is currently the only study with positive results in MOGAD,” Levy stated.

MOGAD is an antigen-specific autoimmune disease that attacks the MOG protein on the outside of myelin sheaths in the central nervous system, leading to demyelination and neurologic disability.

“The most common sites of attack are the optic nerves, spinal cord, and the brain — and the brain especially in children,” Levy said. “These attacks tend to be severe, leading to hospitalization, and the diagnosis is confirmed upon positive serology for the MOG antibody.”

Satralizumab, approved in 2020 to treat aquaporin-4 seropositive neuromyelitis optica spectrum disorder, is a monoclonal antibody that blocks the IL-6 receptor (IL-6R), inhibiting IL-6 signaling.

IL-6 signaling is hypothesized to play a role in the pathogenesis of MOGAD, Levy noted. MOGAD is associated with elevated IL-6 levels in cerebrospinal fluid, and observational data have suggested that IL-6R inhibition may help MOGAD attacks.

METEOROID was a randomized, double-blind study that included patients aged 12 years and older with relapsing MOGAD. Participants were eligible if they had experienced at least one relapse in the previous 12 months or two or more relapses in the previous 24 months.

The primary outcome was the time to first relapse “which, if adjudicated as a true relapse, would then bump the patient to the open-label extension study. This ensured that patients would not suffer more than one relapse in the double-blind period,” Levy explained.

“A true relapse was considered any symptomatic attack of optic neuritis transverse myelitis or brain attack that resulted in neurological disability and could be confirmed by MRI with a new or enhancing T2 lesion,” he added. “There was a rigorous adjudication process by committee that reviewed each relapse to determine if it met criteria.”

Participants were randomized to satralizumab or placebo, with or without concomitant immunosuppressive therapy. Satralizumab was administered subcutaneously at weeks 0, 2, 4, and every 4 weeks after that.

There were 68 patients in the satralizumab arm; their mean age was 41.5 years. Most (72%) experienced optic neuritis during their last relapse and 66% used concomitant immunosuppressive therapy. There were 64 patients in the placebo group with similar baseline characteristics.

On key secondary endpoints, satralizumab reduced the annualized rate of adjudicated relapses by 66.3% (P=0.0030), the annualized rate of active lesions by 78.5% (P=0.0026), and the proportion of participants receiving rescue therapy by 72.5% (P=0.0024), compared with placebo. There was no significant difference between the satralizumab and placebo groups in the adjusted annualized rate of hospitalizations.

The rates of adverse events and infections were comparable between groups. Rates of serious adverse events were low and unrelated to treatment, and treatment discontinuation rates were low. One death occurred — a patient with malignant melanoma who died shortly after enrollment — which was unrelated to satralizumab, Levy noted.

“We have experience with satralizumab in neuromyelitis optica spectrum disorder, which has been approved for about 6 years,” he pointed out. “We kind of knew what to expect, and overall the number of adverse events were nearly the same in both arms.” No new or unexpected safety signals were observed, he added.

The open-label extension study of satralizumab in MOGAD is ongoing, Levy said. Drugmaker Roche stated that it plans to submit the METEOROID data to the FDA later this year.

Please enable JavaScript to view the comments powered by Disqus.