Molecular genetics & genomic medicine · 2025
Historical Control Analysis Demonstrates Greater Long-Term Reduction in Plasma Globotriaosylceramide (Gb3) by Venglustat Compared With Placebo or Agalsidase Beta in Male Patients With Classic Fabry Disease.
СтатьяРандомизированное исследованиеКлиническое исследование II фазыКлиническое исследование III фазыНазвание и аннотация: Перевод в очереди
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Germain Dominique P, DasMahapatra Pronabesh, Liu Shiguang, Deegan Patrick, Ortiz Alberto, Modur Vijay, Wilcox William R
Аннотация
PURPOSE: To evaluate the disease biomarker response of venglustat in patients with Fabry disease (FD), utilizing data from a single-arm phase 2 study of venglustat and a placebo-controlled phase 3 study of agalsidase beta through historical control and case-matched analyses.
METHODS: Eleven venglustat-treated male patients with classic FD in the phase 2 study were matched with placebo- or agalsidase beta-treated patients from the phase 3 study based on propensity scores at baseline. Changes from baseline in plasma globotriaosylceramide (GL-3 or Gb3) concentrations were analyzed at approximately 6-36 months.
RESULTS: Venglustat treatment resulted in greater significant reductions in plasma GL-3 concentrations at 6 months from baseline vs. placebo (mean difference -2.56 μg/mL, p < 0.001), and at 24 and 36 months from baseline vs. agalsidase beta (mean difference -1.8 μg/mL, p < 0.05 and -2.35 μg/mL, p < 0.01, respectively). GL-3 concentrations continued to decline with venglustat for up to 3 years without plateauing.
CONCLUSIONS: Venglustat showed significantly greater reductions in plasma GL-3 concentrations than placebo after 6 months and agalsidase beta after 24 and 36 months. These findings support the potential of long-term venglustat treatment to reduce GL-3 accumulation in patients with classic FD. Further studies are needed to confirm clinical benefit.
METHODS: Eleven venglustat-treated male patients with classic FD in the phase 2 study were matched with placebo- or agalsidase beta-treated patients from the phase 3 study based on propensity scores at baseline. Changes from baseline in plasma globotriaosylceramide (GL-3 or Gb3) concentrations were analyzed at approximately 6-36 months.
RESULTS: Venglustat treatment resulted in greater significant reductions in plasma GL-3 concentrations at 6 months from baseline vs. placebo (mean difference -2.56 μg/mL, p < 0.001), and at 24 and 36 months from baseline vs. agalsidase beta (mean difference -1.8 μg/mL, p < 0.05 and -2.35 μg/mL, p < 0.01, respectively). GL-3 concentrations continued to decline with venglustat for up to 3 years without plateauing.
CONCLUSIONS: Venglustat showed significantly greater reductions in plasma GL-3 concentrations than placebo after 6 months and agalsidase beta after 24 and 36 months. These findings support the potential of long-term venglustat treatment to reduce GL-3 accumulation in patients with classic FD. Further studies are needed to confirm clinical benefit.