Sanofi reported positive results from its phase 3 LEAP2MONO study, showing that Venglustat met all primary endpoints and three of four key secondary endpoints in patients with type 3 Gaucher disease (GD3), a rare neurological lysosomal storage disorder with no approved treatments for central nervous system involvement.
The LEAP2MONO study (NCT05222906) evaluated once-daily oral venglustat in adults and paediatric patients aged 12 years and older with neurological manifestations of GD3.
At week 52, patients receiving venglustat demonstrated statistically significant improvements in neurological outcomes compared with enzyme replacement therapy (ERT), based on changes in the modified Scale for the Assessment and Rating of Ataxia (SARA) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores (p=0.007). Venglustat also matched ERT on systemic disease measures, including spleen and liver volume and haemoglobin levels.
Venglustat is an investigational, brain-penetrant glucosylceramide synthase inhibitor designed to reduce abnormal accumulation of glycosphingolipids, a key driver of disease progression in GD3. The study results will be presented this week as late-breaking research at the 22nd annual WORLDSymposium™.
Sanofi highlighted that it will pursue global regulatory submissions for venglustat in GD3. The drug was generally well tolerated in the study, with no new safety signals observed. The most common adverse events reported in the venglustat arm included headache, nausea, spleen enlargement and diarrhoea.
Venglustat is also being evaluated in Fabry disease. In the phase 3 PERIDOT study (NCT05206773), the drug did not demonstrate superiority over placebo on the primary patient-reported endpoint, although reductions in neuropathic and abdominal pain were observed in both treatment arms. Further analyses are ongoing, and a second phase 3 Fabry disease study, CARAT (NCT05280548), assessing effects on left ventricular mass index, is currently underway.
Sanofi currently markets multiple therapies for Gaucher and Fabry diseases, including Cerezyme, Cerdelga and Fabrazyme. In January 2026, the US approved an expanded label for Cerezyme to include non-central nervous system manifestations of GD3, based on real-world evidence from the International Collaborative Gaucher Group Registry.
The positive LEAP2MONO results position venglustat as a potential first-in-class therapy for addressing the neurological aspects of GD3, reinforcing Sanofi’s commitment to advancing treatments for rare lysosomal storage disorders.
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