Positive results from the phase 3 LEAP2MONO study show that pharma powerhouse Sanofi’s investigational drug venglustat have demonstrated breakthrough results in adults and pediatric patients with neurological manifestations of type 3 Gaucher disease (GD3), a rare lysosomal storage disorder.
Venglustat, a glucosylceramide synthase inhibitor (GCSi), works by reducing the abnormal buildup of sugar-and-fat molecules in cells and organs. Unlike other therapies, it crosses the blood-brain barrier to target neurological aspects of GD3—an area with no currently approved treatments.
"These findings underscore Sanofi's commitment to rare disease research and the promise we aim to deliver for people living with these conditions," said Houman Ashrafian, Executive Vice President and Head of Research and Development at Sanofi.
"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. Most importantly, none of this would be possible without the courage of the patients and families who participate in our studies, and for that we owe them a debt of gratitude.”
In LEAP2MONO, patients receiving venglustat showed statistically significant improvements in neurological symptoms, measured by the Scale for Assessment and Rating of Ataxia (SARA) modified total score and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at week 52, compared with enzyme replacement therapy (ERT). Venglustat performed comparably to ERT on non-neurological outcomes, including spleen and liver volume changes and hemoglobin levels.
Venglustat is also under investigation for Fabry disease. Phase 3 PERIDOT study data showed reductions in neuropathic and abdominal pain in both study arms, though the primary endpoint was not met. Additional analyses are ongoing, and results will be shared at a future medical meeting. Another phase 3 study, CARAT (NCT05280548), is evaluating venglustat’s impact on left cardiac ventricular mass index in Fabry disease patients.
The drug was generally well tolerated, with no new safety signals. In LEAP2MONO, the most common adverse events among the 21 patients receiving venglustat were headache (14.3%), nausea (14.3%), spleen enlargement (14.3%), and diarrhea (14.3%), compared with 22 patients on ERT (headache 18.2%, nausea 4.5%, spleen enlargement 0%, diarrhea 0%).
Sanofi plans global regulatory filings for venglustat in GD3. The drug remains investigational and has not yet been evaluated by any regulatory authority.
