Uplizna treatment shows greater improvement in myasthenia gravis compared with placebo

Key takeaways:

• Those treated with Uplizna showed greater improvement on all myasthenia gravis metrics vs. placebo.
• Safety profile for the drug was consistent with previously known applications.

IV administration of Uplizna was safe and shown to be more efficacious for those with generalized myasthenia gravis compared with placebo at week 26, according to a presentation from AANEM.

“While other treatments are available, there still are patients with inadequate response and disease control along with an ongoing need for options that reduced treatment burden and less frequent dosing ,” Richard J. Nowak, MD, MS, director of the Myasthenia Gravis Clinic at Yale University, told Healio in an email. “This is important as prolonged high-dose steroid use can have harmful effects and contribute to the overall burden of disease.”

Nowak and colleagues sought to examine the safety and efficacy of Uplizna (inebilizumab-cdon, Amgen), a monoclonal antibody with CD19 B-cell depleting properties, in adults with generalized myasthenia gravis (gMG) who were both acetylcholine receptor autoantibody positive (AChR+) and muscle-specific kinase autoantibody positive (MuSK+).

They conducted the MINT clinical trial, a phase 3, randomized, double-blind, multicenter controlled study at 79 sites in 18 countries, predominantly in the Northern Hemisphere. A total of 238 individuals with gMG (AChR+, n = 190; MuSK+, n = 48) were included, and following a screening period of at least 4 weeks, were randomized 1:1 to receive 300 mg IV administration of inebilizumab or placebo. Those in the AChR+ group were treated for 52 weeks, and those in the MuSK+ group for 26 weeks. Loading doses were administered on days 1 and 15 for both treatment cohorts. Following initial randomization, participants could enter an open-label extension with inebilizumab treatment every 6 months for 3 years, or continue with an additional safety follow-up interval of up to 2 years.

Additional protocol required a taper to 5 mg per day by week 24 for those already treated with corticosteroids.

The study’s primary endpoint was the change from baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score at week 26 in the combined gMG population. Secondary endpoints included change from baseline in scores from a battery of additional gMG-related metrics for both types of study enrollees.

According to results, by week 26, the mean reduction in MG-ADL score for those in the treatment group was 4.2 compared with 2.2 for the placebo group. That significant change, as well as significant difference between change from the treatment to placebo cohorts, was constant for all other gMG metrics.

Data further showed that treatment was generally well-tolerated and safe. Ten serious treatment-emergent adverse events (TEAEs) were recorded in the treatment group and 16 given placebo, with three deaths reported (one in the treatment group, two in the placebo group). The most common TEAEs were COVID-19, nasopharyngitis, infusion-related reaction and headache.

“Inebilizumab is unique in that it targets specific B-cells which are upstream immunopathogenic disease drivers and represents a novel approach to the management of myasthenia gravis,” Nowak told Healio. “Topline study results support the role of anti-CD19 B-cell depletion for the treatment of [generalized myasthenia gravis].”

Reference:

Amgen presents positive phase 3 data for uplizna (INEBILIZUMAB-CDON) in generalized myasthenia gravis at AANEM 2024. https://www.amgen.com/newsroom/press-releases/2024/10/amgen-presents-positive-phase-3-data-for-uplizna-inebilizumabcdon-in-generalized-myasthenia-gravis-gmg-at-aanem-2024. Published Oct. 15, 2024. Accessed Nov. 6, 2024.