Sanofi’s venglustat accepted for priority review in the US to treat type 3 Gaucher disease

The US Food and Drug Administration (FDA) has granted priority review to the new drug application (NDA) for venglustat, a novel, investigational oral glucosylceramide synthase inhibitor (GCSi), for the treatment of type 3 Gaucher disease (GD3), a rare lysosomal storage disorder.

If approved, venglustat would become the first treatment available in the US to address the progressive neurological manifestations associated with GD3 and expand Sanofi’s portfolio of treatment options for patients living with lysosomal storage diseases. The target action date for the FDA decision is November 25, 2026.

Gaucher disease is marked by the abnormal buildup of sugar-and-fat molecules called glycosphingolipids (GSL) in the spleen, liver, bone marrow, and lungs. In patients with GD3, these molecules also accumulate in the central nervous system (CNS) where they drive neuroinflammation, which can result in neurological manifestations, including cognitive deficits and difficulty in coordination and balance (ataxia), in addition to the disease’s systemic effects. There are currently no approved targeted treatments that specifically address the neurological symptoms of GD3. By crossing the blood brain barrier, venglustat has the potential to treat neurological manifestations of GD3.

The NDA is supported by positive data from the LEAP2MONO phase 3 study (clinical study identifier: NCT05222906), evaluating the efficacy and safety of venglustat in adults and pediatric patients, with neurological manifestations of GD3, who previously achieved stabilization of systemic manifestations with enzyme replacement therapy (ERT). In results shared at the WORLDSymposium^TM earlier this year, venglustat met both of the study’s primary endpoints and three out of four key secondary endpoints. In the study, venglustat was well tolerated overall with no new safety signals compared with previous studies. The most commonly reported adverse events were headache (14.3% in the venglustat arm versus 18.2% in the ERT arm), nausea (14.3% versus 4.5%), spleen enlargement (14.3% versus 0), and diarrhea (14.3% versus 0).

Venglustat previously earned breakthrough therapy designation and fast-track designation from the FDA for its potential in GD3, as well as orphan designation for GD3 in the US, EU, and Japan. Venglustat is also currently under regulatory review for GD3 in the EU. Sanofi will pursue additional global regulatory filings for venglustat in GD3 in 2026.

The safety and efficacy of venglustat for GD3 have not been evaluated by any regulatory authority.

Priority review is given to regulatory applications seeking approval for therapies that have the potential to provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.