Sanofi’s Drug Meets Primary Endpoints in Type 3 Gaucher Disease Study

Sanofi said its experimental therapy venglustat met the primary and three of four key secondary endpoints in adults and pediatric patients with neurological manifestations of type 3 Gaucher disease, a rare lysosomal storage disorder.

Venglustat was well tolerated overall, with no new safety signals compared with previous studies.

The company said it will pursue global regulatory filings for venglustat in type 3 Gaucher disease (GD3). Venglustat is experimental, and its safety and efficacy have not been evaluated by any regulatory authority.

Gaucher disease (GD) is a rare inherited lysosomal storage disorder that results from a deficiency of the enzyme glucocerebrosidase, leading to the accumulation of molecules called glycosphingolipids (GSLs), particularly in macrophages of the spleen, liver, bone marrow, and lungs. There are three major forms of Gaucher disease: GD1, which is characterized by absent or late central nervous system (CNS) involvement; GD2, the acute neuronopathic form; and GD3, the chronic neuronopathic form.

In people with GD3, accumulation of GSLs in the CNS can result in neurological manifestations, including ataxia and cognitive deficits, in addition to the systemic manifestations seen in GD1, such as liver and spleen enlargement, anemia, thrombocytopenia, and bone disease. Systemic manifestations of GD3 are treated with enzyme replacement therapy, but there are no approved treatments for the neurologic manifestations of GD3.

Venglustat, an investigational glucosylceramide synthase inhibitor (GCSi) that crosses the blood-brain barrier, works by reducing the abnormal accumulation of sugar-and-fat molecules in cells and organs. It is designed to target some of the neurological aspects of GD3 that currently lack approved therapies. The therapy is also being studied in Fabry disease, another lysosomal storage disorder.

Venglustat has previously been granted orphan designation in the United States, the European Union, and Japan for both GD3 and Fabry disease. It also received fast-track designation in the United States for its potential use in GD3 and Fabry disease.

“What excites us most is the potential to address critical unmet medical needs. A daily pill could make a serious difference for Gaucher patients facing neurological challenges,” said Houman Ashrafian, executive vice president and head of research and development at Sanofi.