Eliglustat

Sanofi (Euronext: SAN; Nasdaq: SNY) has received priority review from the US FDA for a new drug application (NDA) for venglustat, an investigational oral glucosylceramide synthase inhibitor (GCSi), seeking approval in patients with type 3 Gaucher disease (GD3) — a rare lysosomal storage disorder with progressive neurological involvement for which no targeted pharmacological treatment currently exists in the US. The NDA seeks approval of venglustat specifically to address the neurological manifestations of GD3, including cerebellar ataxia and cognitive deficits, in adult and pediatric patients who have previously achieved stabilization of systemic disease manifestations with enzyme replacement therapy (ERT). The US FDA has assigned a target action date of November 25, 2026. Venglustat previously received breakthrough therapy designation, fast-track designation, and orphan designation in the US for GD3. A parallel regulatory review is also underway in the EU, and Sanofi said it plans to pursue additional global filings for the indication in 2026. The NDA is supported by data from the LEAP2MONO Phase III study (NCT05222906), a randomized, double-blind, double-dummy, active-comparator trial evaluating venglustat against intravenous ERT in patients aged 12 and older with GD3. Forty-three patients were randomized 1:1 to receive once-daily oral venglustat plus placebo infusion, or ERT every two weeks plus placebo tablet. Eligible patients were required to have received ERT for at least three years and to have met therapeutic goals for systemic disease control prior to enrollment. The trial’s co-primary endpoints were change from baseline to week 52 in the Scale for Assessment and Rating of Ataxia (SARA) modified total score and change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score. Venglustat met both primary endpoints, with a reported p-value of 0.007. The drug also met three of four key secondary endpoints. Systemic secondary endpoints included percent change in spleen volume, liver volume, platelet count, and hemoglobin levels. Biomarker endpoints assessed percent change in cerebrospinal fluid and plasma glucosylceramide (GL-1) and lyso-GL-1. Venglustat was described as generally well tolerated in the trial, with no new safety signals identified relative to earlier studies. The most commonly reported adverse events included headache (14.3% in the venglustat arm versus 18.2% in the ERT arm), nausea (14.3% versus 4.5%), spleen enlargement (14.3% versus 0), and diarrhea (14.3% versus 0). The open-label phase of LEAP2MONO is ongoing, and Sanofi said results will be presented when available. Venglustat is a brain-penetrant, oral small-molecule inhibitor of glucosylceramide synthase, the enzyme responsible for the committed step in glycosphingolipid biosynthesis. By reducing upstream substrate production, it functions as a substrate reduction therapy (SRT), a mechanistic class that also includes the approved agents eliglustat (Cerdelga) and miglustat (Zavesca). Neither of those agents, however, was developed or approved for GD3, and neither demonstrates meaningful CNS penetration — a critical limitation given that the neurological manifestations of GD3 are driven by glycosphingolipid accumulation in the central nervous system. ERT, the current clinical standard for GD3, addresses systemic features such as organomegaly, cytopenias, and bone disease, but does not cross the blood-brain barrier and has no demonstrated effect on neurological progression. In January 2026, the US FDA expanded the label for imiglucerase (Cerezyme), also a Sanofi product, to include a GD3 indication — but that approval was based on systemic outcomes data from an observational registry and does not address the neurological dimension of the disease. If approved, venglustat would represent the first US-authorized therapy specifically indicated for the neurological manifestations of GD3, filling a gap that has persisted throughout the decades-long history of Gaucher disease treatment. The filing adds to a competitive landscape in which no other late-stage CNS-directed agent for GD3 is currently identified in the public domain, positioning venglustat as a potential first-mover in a narrow but clinically distinct patient population. This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/ Your email address will not be published. Required fields are marked * Comment * Name * Email * Website Privacy Terms About Us Copyright © 2026. AllSci Corp. All rights reserved.