The FDA has granted priority review to Sanofi’s oral therapy venglustat for type 3 Gaucher disease, with a PDUFA date of November 25, 2026. If approved, it would be the first US treatment to target neurological manifestations of the rare lysosomal disorder.
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
The US Food and Drug Administration (FDA) has accepted Sanofi’s new drug application (NDA) for venglustat in type 3 Gaucher disease (GD3) and granted priority review, setting a Prescription Drug User Fee Act (PDUFA) target action date of November 25, 2026. If approved, venglustat would become the first US therapy to directly address the neurological manifestations of GD3, a rare lysosomal storage disorder with significant unmet need.
First CNS-Targeted Therapy in GD3
Current treatments, including enzyme replacement therapy (ERT), primarily manage systemic disease but have limited activity in the central nervous system (CNS). GD3 is characterized by glycosphingolipid accumulation in organs such as the spleen, liver, bone marrow, and lungs, as well as in the CNS, where it drives neuroinflammation and progressive neurological decline. Patients often develop cognitive impairment, ataxia, and other disabling symptoms.
Venglustat, an oral glucosylceramide synthase inhibitor (GCSi), crosses the blood–brain barrier to reduce pathogenic glycosphingolipid production. This brain-penetrant mechanism differentiates it from standard ERT and positions it as a potential disease-modifying therapy for neurological complications.
Phase 3 LEAP2MONO Trial
The NDA is supported by data from the pivotal Phase 3 LEAP2MONO trial (NCT05222906), a double-blind, double-dummy study comparing once-daily oral venglustat with intravenous ERT in 43 adolescents and adults (≥12 years) with GD3 who had achieved stable systemic control on ERT.
At Week 52, venglustat met both primary endpoints:
- Improvement in neurological function measured by the Scale for the Assessment and Rating of Ataxia (SARA) modified total score.
- Cognitive performance assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score.
The therapy also met three of four key secondary endpoints. Safety findings were consistent with prior studies, with the most common adverse events including headache, nausea, spleen enlargement, and diarrhea. No new safety signals emerged.
Regulatory Status
Venglustat has previously received FDA breakthrough therapy and fast-track designations for GD3, along with orphan drug designation in the US, EU, and Japan. Regulatory review is also underway in Europe, with additional global filings planned during 2026. The LEAP2MONO trial continues in its open-label extension phase, with long-term data expected in future updates.
Reference
About the Writer
Nikita Jha, BPharm (LinkedIn) a pharmacy graduate specializing in medical writing, with a strong ability to interpret complex medical and regulatory information and translate it into clear, accurate, and evidence-based healthcare content. Known for her attention to detail and precision, she focuses on delivering high-quality scientific communication that supports drug safety and informed decision-making.