FDA Grants Priority Review to Sanofi's Venglustat for Type 3 Gaucher Disease
FDA granted priority review to Sanofi's venglustat for type 3 Gaucher disease (action date Nov 25, 2026). Phase 3 LEAP2MONO data showed venglustat met both primary endpoints and three of four key secondary endpoints.
The U.S. Food and Drug Administration (FDA) has granted priority review to Sanofi's new drug application (NDA) for venglustat, an investigational oral glucosylceramide synthase inhibitor (GCSi), for the treatment of type 3 Gaucher disease (GD3). If approved by the target action date of November 25, 2026, venglustat would become the first treatment available in the United States to address the progressive neurological manifestations of GD3.
The NDA is supported by positive data from the LEAP2MONO phase 3 study (NCT05222906), a double-blind, double-dummy, active-comparator, two-arm trial that randomized 43 adults and pediatric patients aged 12 and older with neurological manifestations of GD3 to receive either once-daily oral venglustat and placebo infusion or enzyme replacement therapy (ERT) and placebo tablet. Patients had been treated with ERT for at least three years and achieved therapeutic goals for systemic disease manifestations. Venglustat met both primary endpoints — change in the modified Scale for Assessment and Rating of Ataxia (SARA) total score and change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score — and three out of four key secondary endpoints at week 52. Patients receiving venglustat showed statistically significant neurological improvement versus those receiving ERT (p=0.007). Venglustat performed as well as ERT on non-neurological outcomes, including changes in spleen volume, liver volume, and hemoglobin levels. Results were shared at the 22nd annual WORLDSymposium as late-breaking research.
Venglustat was generally well tolerated, with no new safety signals compared with previous studies. The most commonly reported adverse events in the venglustat arm (n=21) versus the ERT arm (n=22) were headache (14.3% vs 18.2%), nausea (14.3% vs 4.5%), spleen enlargement (14.3% vs 0), and diarrhea (14.3% vs 0). The trial continues in its open-label phase, with results to be released when available.
Venglustat has previously received breakthrough therapy, fast-track, and orphan designations from the FDA for GD3, and orphan designation in the EU and Japan. The therapy is also under regulatory review in the EU, and Sanofi plans to 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.
GD3 is a rare lysosomal storage disorder marked by the abnormal buildup of glycosphingolipids (GSL) in the spleen, liver, bone marrow, and lungs. In patients with GD3, these molecules also accumulate in the central nervous system (CNS), driving neuroinflammation that can result in cognitive deficits and ataxia. There are currently no approved targeted treatments that specifically address the neurological symptoms of GD3. Venglustat is designed to cross the blood-brain barrier to target underlying CNS pathology.
Venglustat is also being studied for Fabry disease. Data from the phase 3 PERIDOT study (NCT05206773) showed that the primary endpoint was not met, with reductions in neuropathic and abdominal pain observed in both arms; additional analyses are ongoing. A second phase 3 study, CARAT (NCT05280548), evaluating the effect of venglustat on left cardiac ventricular mass index in Fabry disease, is ongoing. In January 2026, the US approved an expanded label for Cerezyme to include non-CNS manifestations of GD3, based on real-world evidence from the International Collaborative Gaucher Group Gaucher Registry, allowing Cerezyme to be prescribed globally to patients with either GD1 or GD3.