SAVANNAH, GEORGIA — , new phase 3 data showed.
“Based on these results, we have demonstrated that targeting B cells, including the antibody-secreting cells, is beneficial, and there is likely a role for this kind of therapeutic strategy for patients with myasthenia gravis,” said senior investigator Richard Nowak, MD.
The findings were published and presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
Largest Cohort of Muscle-Specific Kinase (MuSK) Antibody–Positive Disease
The Myasthenia Gravis INebilizumab Trial study enrolled 238 participants, 60.8% women, mean age 47.5 years, from 79 sites in 18 countries. The participants were divided into two cohorts: 190 acetylcholine receptor (AChR) autoantibody–positive patients and 48 MuSK autoantibody–positive patients.
“This is the largest enrolled cohort of MuSK antibody–positive disease in a placebo-controlled trial to date,” said Nowak, director of the Yale Myasthenia Gravis Clinic and associate professor of neurology at Yale School of Medicine, in New Haven, Connecticut.
Both groups had similar gMG duration (mean 6.7 and 5.2 years for AChR+ and MuSK+ patients, respectively) and disease severity based on Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) baseline score. In addition, more than 80% of participants were on a prednisone equivalent dose greater than 5 mg daily at study entry.
Participants were randomly assigned to receive intravenous (IV) inebilizumab or IV placebo for 52 weeks (AChR+ group) or 26 weeks (MuSK+ group). In addition, study participants who were taking corticosteroids were tapered down starting at week 4 to prednisone 5 mg per day by week 24.
The trial met its primary endpoint, with a statistically significant change from baseline in MG-ADL and with a reduction of 4.2 points for inebilizumab versus 2.2 for placebo (P < .0001) at week 26 for the combined study population.
“You can see that the trend is actually going toward separation of the two groups after week 8 in the combined population,” said Nowak. Key secondary endpoints also showed statistically significant and clinically meaningful change from baseline compared with placebo.
This included a statistically significant change in QMG score inebilizumab compared with placebo for the combined population, a reduction of 4.8 versus 2.3 points, respectively, at week 26 (P = .0002).
In addition, both MG-ADL and QMG scores in the AChR+ subgroup were superior for inebilizumab versus placebo at week 26, with reductions of 4.2 versus 2.4, and 4.4 versus 2.0; P = .0015 and P = .0011, respectively.
In the MuSK+ subgroup, inebilizumab-treated patients had better MG-ADL scores than placebo-treated patients, with reductions of 3.9 versus 1.7 points, respectively, at week 26, although this difference did not meet statistical significance.
“There were no increased safety incidents in the inebilizumab-treated patients versus placebo, and a similar percentage of safety incidents in the AChR–positive and MuSK–positive groups. There were three deaths reported, all likely related to myasthenic crisis,” he said.
Nowak said that inebilizumab is “unique from the other currently FDA-approved medications for myasthenia gravis in that it’s targeting the upstream immunopathogenic mechanism of disease, specifically B cells — and B cells that are actually antibody-secreting cells.”
“It is targeting the factories of autoantibody production, whereas an FcRn antagonist, for example, is not targeting those factories but rather targeting what’s being produced — the immunoglobulins, IgGs in general,” he added.
Nowak said that what is particularly exciting about the drug is that the schedule is not very frequent. It begins with an initial IV infusion, followed by a second infusion 2 weeks later and a third infusion 6 months after that, so that patients are treated approximately every 6 months. This is in contrast to some other targeted therapies, where failing to address the underlying factors driving immunopathogenesis necessitates more regular and frequent medication administration.