The FDA has granted Breakthrough Therapy designation to Sanofi’s venglustat, an investigational oral glucosylceramide synthase inhibitor, for treating neurological manifestations of type 3 Gaucher disease. The designation is based on Phase 3 LEAP2MONO study data showing statistically significant improvements in neurological symptoms compared with imiglucerase enzyme replacement therapy.
Type 3 Gaucher disease is a rare inherited lysosomal storage disorder caused by glucocerebrosidase enzyme deficiency, leading to glycosphingolipid accumulation. Symptoms include ataxia, cognitive decline, liver and spleen enlargement, anemia, and bone disease. Currently, no approved treatments exist for the neurological symptoms of the disease.
Venglustat works by reducing abnormal glycosphingolipid accumulation and is able to cross the blood-brain barrier to address neurological effects, a critical differentiator from existing enzyme replacement therapies that cannot reach the central nervous system. The drug was well-tolerated in the study with no new safety signals reported.