Positive results from the phase 3 LEAP2MONO study (clinical study identifier: NCT05222906) showed that venglustat met its primary endpoint and three of four key secondary endpoints in adults and paediatric patients aged 12 years and older with neurological manifestations of type 3 Gaucher disease (GD3), a rare lysosomal storage disorder.
Notably, the findings mark an important advance in addressing neurological symptoms of GD3, an area where no approved therapies currently exist.
Venglustat Targets Unmet Neurological Needs
Venglustat is an investigational glucosylceramide synthase inhibitor (GCSi) designed to reduce the abnormal buildup of sugar-and-fat molecules in cells and organs. Importantly, the oral therapy crosses the blood–brain barrier, enabling it to target neurological manifestations of GD3.
Meanwhile, Sanofi continues its long-standing engagement with the Gaucher disease community, reinforcing more than four decades of commitment to rare disease research and care.
Findings to Be Presented at WORLDSymposium™
The study results will be presented this week as late-breaking research at the 22nd annual WORLDSymposium™, a leading global forum for lysosomal disease research.
Sanofi Highlights Commitment to Rare Disease Innovation
Commenting on the findings, Houman Ashrafian, Executive Vice President and Head of Research and Development at Sanofi, emphasised the company’s focus on addressing unmet needs in rare diseases.
“These findings underscore Sanofi’s commitment to rare disease research and the promise we aim to deliver for people living with these conditions,” he said. “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.”
Significant Neurological Improvements at 52 Weeks
In the LEAP2MONO study, patients with GD3 receiving venglustat demonstrated statistically significant improvements in neurological symptoms at week 52 compared with those receiving enzyme replacement therapy (ERT).
Specifically, researchers measured improvements using two validated assessments:
- the Scale for the Assessment and Rating of Ataxia (SARA) modified total score, and
- the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
The results reached statistical significance (p=0.007).
In addition, venglustat performed comparably to ERT on non-neurological outcomes, including spleen volume, liver volume and haemoglobin levels, which were key secondary endpoints of the study.
Ongoing Studies in Fabry Disease
Beyond GD3, researchers are also evaluating venglustat in Fabry disease, another rare lysosomal storage disorder.
Data from the phase 3 PERIDOT study (clinical study identifier: NCT05206773) showed reductions in neuropathic and abdominal pain in both treatment arms. However, the study did not meet its primary endpoint. Further analyses are ongoing, with additional findings expected at a future medical meeting.
At the same time, a second phase 3 study, CARAT (clinical study identifier: NCT05280548), continues to evaluate the effect of venglustat on left ventricular mass index in men and women with Fabry disease.
Favourable Safety Profile Observed
Overall, venglustat demonstrated a favourable safety profile, with no new safety signals compared with earlier studies.
In LEAP2MONO, the most commonly reported adverse events among patients receiving venglustat (21 individuals), compared with those receiving ERT (22 individuals), included:
- headache (14.3% vs 18.2%),
- nausea (14.3% vs 4.5%),
- spleen enlargement (14.3% vs 0), and
- diarrhoea (14.3% vs 0).
Regulatory Plans and Existing Gaucher Portfolio
As per the Sanofi Press release, based on these findings, Sanofi plans to pursue global regulatory filings for venglustat in GD3. However, venglustat remains investigational, and regulatory authorities have not yet evaluated its safety or efficacy.
Currently, Sanofi markets Fabrazyme for Fabry disease and Cerezyme and Cerdelga for Gaucher disease worldwide. In January 2026, the US approved an expanded label for Cerezyme to include non-central nervous system manifestations of GD3, building on its existing approval for GD1.
This label expansion relied exclusively on real-world evidence from the International Collaborative Gaucher Group Gaucher Registry, allowing Cerezyme to be prescribed globally for patients with either GD1 or GD3.