The US Food and Drug Administration (FDA) has granted priority review to Sanofi’s New Drug Application (NDA) for venglustat, an investigational oral Glucosylceramide Synthase Inhibitor (GCSi) being developed for the treatment of type 3 Gaucher Disease (GD3), a rare lysosomal storage disorder with severe neurological complications.

If approved, venglustat would become the first therapy available in the United States specifically designed to address the progressive neurological manifestations associated with GD3. The therapy would also expand Sanofi’s growing portfolio of treatments for lysosomal storage disorders. The FDA has set a target action date of November 25, 2026, for its regulatory decision.

Gaucher disease is caused by the abnormal accumulation of glycosphingolipids in organs such as the spleen, liver, lungs and bone marrow. In patients with GD3, these substances also accumulate in the central nervous system, leading to neuroinflammation and neurological complications including cognitive impairment, coordination difficulties and ataxia. Existing therapies primarily address the systemic symptoms of the disease and do not specifically target neurological manifestations.

Venglustat is designed to cross the blood-brain barrier, allowing it to potentially reduce the abnormal accumulation of glycosphingolipids within the central nervous system and slow disease progression.

The NDA submission is supported by positive results from the LEAP2MONO phase 3 clinical study, which evaluated the efficacy and safety of venglustat in adults and paediatric patients aged 12 years and older with neurological manifestations of GD3. Participants in the study had previously achieved stabilisation of systemic disease symptoms through Enzyme Replacement Therapy (ERT).

Results presented earlier this year at the WORLDSymposium showed that venglustat met both primary endpoints and three out of four key secondary endpoints in the trial. The study assessed neurological improvements using the Scale for Assessment and Rating of Ataxia (SARA) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

The therapy demonstrated an acceptable safety and tolerability profile consistent with previous studies. The most commonly reported adverse events included headache, nausea, diarrhoea and spleen enlargement.

The LEAP2MONO study is a global double-blind, double-dummy, active-comparator trial involving 43 patients randomised to receive either once-daily oral venglustat with placebo infusion or intravenous ERT with placebo tablets. Patients enrolled in the study had been receiving ERT for at least three years prior to participation.

In addition to neurological outcomes, the study also evaluated systemic disease markers including spleen and liver volume, platelet counts, haemoglobin levels and biomarker changes in cerebrospinal fluid and plasma.

Venglustat has previously received breakthrough therapy designation, fast-track designation and orphan drug designation from the FDA for GD3. The therapy has also been granted orphan designation in the European Union and Japan and is currently under regulatory review in Europe. Sanofi plans to pursue additional global regulatory submissions for GD3 during 2026.

Beyond Gaucher disease, venglustat is also being investigated for other rare disorders linked to glycosphingolipid accumulation, including Fabry disease. The therapy is part of Sanofi’s broader strategy to expand its pipeline of treatments for rare and debilitating diseases using advanced research and development capabilities.

Sanofi stated that the company continues to focus on developing innovative therapies powered by its expertise in immunology, rare diseases and precision medicine to address significant unmet medical needs globally.