Sanofi reported positive Phase 3 LEAP2MONO results showing venglustat improved neurological symptoms in type 3 Gaucher disease (GD3), meeting primary and key secondary endpoints, with global regulatory filings planned
Written By: Pharmacally Medical News Desk
Sanofi announced positive topline results from the Phase 3 LEAP2MONO study (NCT05222906), showing that investigational oral therapy venglustat met its primary endpoint and three of four key secondary endpoints in adults and pediatric patients aged 12 and older with neurological manifestations of type 3 Gaucher disease (GD3).
GD3, a rare lysosomal storage disorder caused by glucocerebrosidase deficiency, leads to glycosphingolipid buildup in organs like the spleen, liver, bone marrow, lungs, and central nervous system, causing ataxia, cognitive impairment, and progressive neurological decline. Unlike enzyme replacement therapy (ERT), which controls systemic symptoms, no approved treatments target GD3’s neurological complications.
The data will appear as late-breaking research at the 22nd annual WORLDSymposium™ this week.
Venglustat, a glucosylceramide synthase inhibitor (GCSi), reduces abnormal sugar-and-fat molecule accumulation in cells and crosses the blood-brain barrier to address unmet neurological needs. In the trial, venglustat outperformed ERT on the primary endpoint a global neurological test score combining the modified Scale for Assessment and Rating of Ataxia (SARA) total score and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) with statistically significant improvements at week 52. It matched ERT on systemic endpoints, including spleen and liver volume changes and hemoglobin levels, suggesting potential to control both neurological and systemic disease.
Safety data showed venglustat was generally well tolerated, with no new signals versus prior studies. Common adverse events included headache (14.3% venglustat vs. 18.2% ERT), nausea (14.3% vs. 4.5%), spleen enlargement (14.3% vs. 0%), and diarrhea (14.3% vs. 0%).
Houman Ashrafian, Sanofi’s Executive Vice President and Head of Research and Development, stated: “These findings underscore Sanofi’s commitment to rare disease research and the promise we aim to deliver for people living with these conditions. What excites us most is the potential to address critical unmet medical needs.”
Sanofi plans global regulatory filings for venglustat in GD3. The company markets Cerezyme and Cerdelga for Gaucher disease and Fabrazyme for Fabry disease; in January 2026, the US expanded Cerezyme’s label for non-CNS GD3 manifestations based on real-world evidence. Cerezyme and Fabrazyme are enzyme replacement therapies (ERTs), while Cerdelga is a substrate reduction therapy (SRT).
Venglustat also advances in Fabry disease programs. The Phase 3 PERIDOT study (NCT05206773) reduced neuropathic and abdominal pain but missed its primary endpoint, with analyses ongoing. The Phase 3 CARAT trial (NCT05280548) evaluates cardiac outcomes.
Fabry disease is a rare inherited lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A, leading to buildup of glycosphingolipids in cells. This progressive accumulation can damage major organs, particularly the kidneys, heart, and nervous system, and often causes neuropathic pain and gastrointestinal symptoms early in life.
Venglustat holds orphan drug designation in the EU, US, and Japan, plus FDA fast-track status for GD3 and Fabry disease.
References
Press Release: Sanofi’s venglustat met all primary endpoints in a phase 3 study of type 3 Gaucher disease, 02 February 2026, https://www.sanofi.com/en/media-room/press-releases/2026/2026-02-02-06-00-00-3229947
Study to Evaluate the Efficacy and Safety of Venglustat in Adult and Pediatric Patients with Gaucher Disease Type 3 (LEAP2MONO), ClinicalTrials.gov ID NCT05222906, https://clinicaltrials.gov/study/NCT05222906
A Study to Evaluate the Effect of Venglustat Tablets on Neuropathic and Abdominal Pain in Male and Female Participants ≥16 Years of Age with Fabry Disease (PERIDOT), ClinicalTrials.gov ID NCT05206773, https://clinicaltrials.gov/study/NCT05206773
A Study to Evaluate the Effect of Venglustat Tablets on Left Ventricular Mass Index in Male and Female Adult Participants With Fabry Disease (CARAT), ClinicalTrials.gov ID NCT05280548, https://clinicaltrials.gov/study/NCT05280548