Understanding the Therapeutic Potential of Inebilizumab in Myasthenia Gravis: Richard Nowak, MD, MS

WATCH TIME: 4 minutes

"Inebilizumab is an anti-CD19 positive B cell depleting biologic, so it's targeting B cells that express the CD19 antigen on their surface. Why that's important is that the antibody-secreting cells, including plasma blasts and certain long-lived plasma cells, express that particular antigen."

Inebilizumab (Uplizna; Amgen), is a humanized, afucosylated IgG1 monoclonal antibody that targets the B cell-specific antigen CD19. The therapy was first tested in trials of systemic sclerosis and relapsing multiple sclerosis (MS) before it entered clinical studies of neuromyelitis optica spectrum disorder (NMOSD). In 2020, the FDA approved inebilizumab as the third marketed treatment for NMOSD, trailing eculizumab (Soliris; Alexion) and satralizumab (Enspryng; Genentech).

Years later, inebilizumab is being tested as a new treatment for patients with myasthenia gravis (MG), another autoimmune disorder. The phase 3 MINT trial (NCT04524273) comprised 238 patients with MG who were randomly assigned 1:1 to either intravenous inebilizumab 300 mg (n = 119) or placebo (n = 119) for a 12-month period. Presented at the 2024 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, held October 15-18, in Savannah, Georgia, the study met its primary end point, with inebilizumab-treated patients demonstrating a statistically significant improvement in Myasthenia Gravis-Activities of Daily Living (MG-ADL) scale vs placebo (–4.2 vs –1.9; P <.0001). MINT, a registrational study, was notable in that it featured the largest cohort of patients with muscle-specific kinase (MuSK) generalized MG (n = 48).

During the meeting, Richard Nowak, MD, MS, an investigator on the trial, sat down to discuss some of the presented data, as well as the mechanism of action behind inebilizumab. Nowak, an associate professor of neurology at Yale School of Medicine and director of the Yale Myasthenia Gravis Clinic, provided comments on primary and secondary outcomes, as well as observed trends in antibody subgroups. In addition, he touched on the observed safety of the therapy, which was consistent with NMOSD trials. Furthermore, he gave insight on the reasons for why inebiluzumab shows promise in MG, focusing on the underlying immunopathogenesis of the disease and highlighting the therapy’s potential in reducing autoantibody production.

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REFERENCE
1. Nowak R, Benetar M, Ciafaloni E, et al. Randomized, double-blind, placebo-controlled, multicenter phase 3 study of inebilizumab in patients with generalized myasthenia gravis (MINT): topline efficacy and safety findings. Presented at: 2024 AANEM annual meeting; October 15-17; Savannah, GA.