Sanofi will take venglustat to regulators for Gaucher disease but an application for Fabry disease is less clear after the failure of a Phase III trial.
Sanofi’s rare disease drug venglustat split a pair of Phase III clinical trials, with success in Gaucher disease but failure in Fabry disease.
The French pharma reported Monday that the glucosylceramide synthase inhibitor (GCSi) spurred neurological improvements in patients with Gaucher who had neurological manifestations. Gaucher is a rare, inherited lysosomal disorder that leads to the buildup of fatty substances in tissue.
In terms of improving neurological symptoms, venglustat outperformed enzyme replacement therapy (ERT), which is the standard of care, at week 52 in the late-stage LEAP2MONO trial. The drug also matched ERT on non-neurological outcomes, such as spleen volume, liver volume and hemoglobin levels, which were key secondary endpoints. On the basis of these results, Sanofi plans to take venglustat to regulators for Gaucher disease.
In Fabry disease, however, the outcome was not as positive. Sanofi reported that the Phase III PERIDOT trial did not meet its main goal of reducing neuropathic and abdominal pain, however, there were reductions in markers of both.
Sanofi is also studying the effect of venglustat on left cardiac ventricular mass index in men and women who have Fabry disease. The Phase III test is ongoing.
The company did not reveal its regulatory plans for Fabry, besides analyzing the results further and waiting for the additional late-stage test.
Sanofi has experience with both diseases; the French pharma manufactures Fabrazyme, an ERT for Fabry, as well as Cerezyme and Cerdelga for Gaucher.
The FDA previously granted fast track designation to venglustat for both Gaucher and Fabry disease. The drug has had a bit of a rocky ride through the clinic so far. In 2024, Sanofi canned a Phase II test of venglustat in the rare genetic disorder GM2 gangliosidosis after a clinical failure, and in 2021, a Phase II/III trial was axed for kidney disease.
