# 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

## TL;DR

Venglustat reduces a harmful substance in the blood of Fabry disease patients more effectively than other treatments over the long term.

## Contribution

Demonstrates venglustat's superior long-term reduction of plasma GL-3 in Fabry disease compared to placebo and agalsidase beta.

## Key findings

- Venglustat reduced plasma GL-3 more than placebo after 6 months.
- Venglustat showed greater GL-3 reduction than agalsidase beta after 24 and 36 months.
- GL-3 levels continued to decrease with venglustat for up to 3 years without plateauing.

## Abstract

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.

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.

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.

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.