The use of chimeric antigen receptor (CAR) T cells could become part of the therapeutic options for patients with myasthenia gravis (MG), according to a study recently published in Lancet Neurology.
“In addition to Descartes-08 appearing to be safe and well tolerated in our study, the magnitude of measured responses is promising, as the proportion of participants in our study who had a decrease in myasthenia gravis scales,” the authors wrote.
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The study team conducted a prospective, multicenter, open-label phase 1b/2a clinical trial to evaluate Descartes-08, an autologous antiB-cell maturation antigen (BCMA) RNA-engineered CAR-T therapy. The trial enrolled adults with generalized MG and a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 6 or higher at 8 sites in the United States, including academic medical centers and community neurology clinics.
In the study’s first phase, the researchers administered 3 escalating doses of Descartes-08 to participants with MGFA disease class 3 to 4 to determine the maximum tolerated dose. In the second phase, individuals with generalized MG and MGFA disease class 2 to 4 received 6 doses of Descartes-08 at the maximum tolerated dose as outpatients. The primary objective was to establish Descartes-08’s safety and tolerability, while secondary objectives involved assessing disease severity and biomarkers.
Out of the 16 individuals screened, 14 enrolled without observing dose-limiting toxicity, cytokine release syndrome, or neurotoxicity. Common adverse events, such as vomiting, nausea, fever, and headache, were present in some patients but resolved within 24 hours of the infusion. The investigators found no association between fevers and increased markers of cytokine release syndrome.
Participants who received Descartes-08 exhibited significant improvements in Myasthenia Gravis Composite score, Quantitative Myasthenia Gravis score, MG severity scales, including MG-ADL score, and Myasthenia Gravis Quality of Life 15-revised score. Notably, these improvements persisted for up to 12 months of follow-up.
The study’s findings indicate that Descartes-08 is a safe and well-tolerated therapy that effectively reduces disease severity in individuals with MG. While these results are promising, it represents the initial step towards making RNA-engineered CAR-T therapy available for autoimmune diseases such as MG.
“Further research is needed to explore its potential in larger patient populations and to determine its applicability to other autoimmune conditions,” the authors noted.
Granit V, Benatar M, Kurtoglu M, et al. Safety and clinical activity of autologous RNA chimericantigen receptor T-cell therapy in myasthenia gravis (MG-001): a prospective, multicentre, open-label,non-randomised phase 1b/2a study. Lancet Neurol. Published online July 1, 2023. doi:10.1016/S1474-4422(23)00194-1