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news.Sanofi has received a priority review from the US Food and Drug Administration (FDA) for its new drug application (NDA) for venglustat, an oral glucosylceramide synthase inhibitor (GCSi) intended for the treatment of type 3 Gaucher disease (GD3).
The LEAP2MONO Phase III trial evaluated venglustat’s efficacy and safety in adults and children aged 12 and above. Credit: Pickadook / Shutterstock.com.
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If approved, venglustat would be the first treatment in the US to address the neurological symptoms of GD3, which currently have no targeted therapies. The decision is anticipated by 25 November 2026.
GD3 is characterised by the accumulation of glycosphingolipids (GSL) in organs such as the spleen, liver, bone marrow, and lungs, as well as in the central nervous system (CNS).
This accumulation leads to neuroinflammation and neurological issues, including cognitive deficits and ataxia, along with the disease’s systemic effects. Venglustat crosses the blood-brain barrier and could treat these neurological manifestations.
The NDA submission relies on positive data from the LEAP2MONO Phase III study.
The trial evaluated venglustat’s efficacy and safety in adults and children aged 12 and above with neurological symptoms of GD3 who had already stabilised systemic symptoms with enzyme replacement therapy (ERT).
Venglustat met both primary endpoints and three out of four secondary endpoints in the study.
Sanofi reported venglustat was generally well tolerated, with headaches, nausea, spleen enlargement, and diarrhoea being the most frequently reported adverse events in the venglustat group, compared with those in the ERT group.
Venglustat has previously received breakthrough therapy, fast-track, and orphan designations from the FDA for GD3 while maintaining orphan status in the EU, Japan, and the US.
The therapy is also under regulatory review in the EU, with further global filings planned this year. The safety and efficacy of venglustat for GD3 are yet to be evaluated by any regulatory authority.
The LEAP2MONO Phase III study is a double-blind, double-dummy, active-comparator, two-arm trial with 43 patients randomised to receive either venglustat and placebo infusion or ERT and placebo tablet.
Primary endpoints included changes in the modified scale for the assessment and rating of ataxia (SARA) and the repeatable battery for the assessment of neuropsychological status (RBANS) scores.
Systemic and biomarker secondary endpoints were also studied. The trial continues in its open-label phase, with results to be released when available.
Venglustat is an investigational, oral GCSi designed to penetrate the brain and potentially address diseases caused by abnormal GSL accumulation, including GD3 and Fabry disease.
In March, Sanofi signed an exclusive global licence agreement with Kali Therapeutics for KT501, a new tri-specific antibody for B cell-mediated autoimmune diseases.
