Sanofi misses in Fabry: Is it time to move on from GCS inhibition in the indication?

Sanofi’s brain-penetrant GCS inhibitor appears to be hitting the mark in Gaucher disease, but its latest readout in another lysosomal storage disease linked to the same pathway — Fabry disease — raises questions about whether GCS inhibition is a viable strategy for improving clinical outcomes in Fabry.

Oral small molecule venglustat is intended to address neurological symptoms not adequately treated by approved enzyme replacement therapies (ERTs). Two lysosomal storage disorders with neurological manifestations are type 3 Gaucher disease, caused by loss of beta-glucosidase function, and Fabry disease, caused by loss of alpha-galactosidase A function...