Sanofi’s Venglustat Demonstrates Superiority Over ERT in Phase 3 Type 3 Gaucher Disease Trial

Sanofi reports a major victory for its rare disease pipeline today. Venglustat met all primary endpoints in the LEAP2MONO Phase 3 study (NCT05222906). The drug showed clinically meaningful efficacy for type 3 Gaucher disease (GD3). This rare lysosomal storage disorder currently lacks treatments for its neurological symptoms. Sanofi now plans to pursue global regulatory submissions for GD3.

Investigational Oral GCSi: Mechanism and Study Design

Venglustat is an investigational oral therapy dosed once daily. It functions as a glucosylceramide synthase inhibitor (GCSi). The drug crosses the blood-brain barrier effectively. It reduces the abnormal buildup of sugar-and-fat molecules in cells. This mechanism targets neurological aspects of GD3 specifically.

The LEAP2MONO study compared venglustat directly against enzyme replacement therapy (ERT). Researchers enrolled adults and pediatric patients aged 12 and older. Participants showed significant improvements in neurological symptoms at week 52. Doctors measured this using the Scale for Assessment and Rating of Ataxia (SARA). They also used the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

Clinical Efficacy: Statistical Superiority Over Standard Care

The study confirmed venglustat’s superiority over ERT for brain-related symptoms (p=0.007). Standard ERT does not address these neurological challenges. Venglustat also performed as well as ERT on non-neurological outcomes. It successfully controlled spleen volume and liver volume. Hemoglobin levels remained stable during the treatment. The trial met the primary endpoint and three key secondary endpoints.

Detailed results will appear this week at the 22nd annual WORLDSymposium™. Sanofi presents this as late-breaking research.

Sanofi’s Commitment to Rare Diseases

Houman Ashrafian, Sanofi’s Head of R&D, highlighted the drug’s potential. He noted that a daily pill could transform patient lives. The company aims to address critical unmet medical needs. Ashrafian thanked the patients and families involved in the studies. Sanofi has supported the Gaucher community for over 40 years.

Venglustat appeared well tolerated in the LEAP2MONO trial. Safety data showed no new signals compared to previous studies. Researchers monitored 21 patients on venglustat and 22 on ERT. Headache occurred in 14.3% of the venglustat group. Nausea affected 14.3% of these patients as well. Spleen enlargement and diarrhea were also reported at 14.3%. The ERT group reported headaches at 18.2% and nausea at 4.5%.

Updates on Fabry Disease Clinical Trials

Sanofi also provided data on venglustat for Fabry disease. The PERIDOT Phase 3 study (NCT05206773) evaluated the drug’s effect on pain. It focused on patient-reported neuropathic and abdominal pain. Reductions in pain occurred in both study arms. However, venglustat did not show statistical superiority. The primary endpoint for PERIDOT was not met.

Further analysis of the PERIDOT data is currently ongoing. Sanofi will share more information at a future medical meeting. The company continues to evaluate the drug in another trial. The Phase 3 CARAT study (NCT05280548) remains active. This study assesses the left cardiac ventricular mass index. It enrolls both men and women with Fabry disease.

Global Regulatory Strategy and Market Landscape

Sanofi prepares for global regulatory filings for venglustat in GD3. The drug remains investigational at this stage. No regulatory authority has yet evaluated its safety or efficacy.

Sanofi currently markets several therapies in this space. These include Fabrazyme for Fabry disease and Cerezyme for Gaucher disease. The US recently expanded the label for Cerezyme in January 2026. It now includes non-central nervous system manifestations of GD3. This approval leveraged real-world evidence from the International Collaborative Gaucher Group Registry. Clinicians can now prescribe Cerezyme globally for both GD1 and GD3.

What Is Gaucher Disease Type 3? Systemic and Neurological Features

Gaucher disease (GD) is a rare inherited lysosomal storage disorder. It results from deficiency of the enzyme glucocerebrosidase. This deficiency causes glycosphingolipid accumulation in macrophages. Affected tissues include the spleen, liver, bone marrow, and lungs. Clinicians classify Gaucher disease into three major clinical types.

GD1 shows little or no central nervous system involvement. GD2 is the acute neuronopathic form with rapid neurological progression. GD3 is the chronic neuronopathic form with ongoing neurological involvement.

In GD3, glycosphingolipids accumulate within the central nervous system. This accumulation leads to ataxia, eye movement disorders, and cognitive impairment. Patients also experience systemic manifestations seen in GD1. These include hepatosplenomegaly, anemia, thrombocytopenia, and bone disease. Enzyme replacement therapy treats systemic symptoms in GD3. However, no approved therapies currently address neurological manifestations

Author

Steven Chung

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