Sanofi’s venglustat receives breakthrough therapy designation for type 3 Gaucher disease in the U.S.

The US FDA has recently granted Breakthrough Therapy designation to venglustat, a novel, investigational oral glucosylceramide synthase inhibitor, for the treatment of neurological manifestations of type 3 Gaucher disease, which is a rare lysosomal storage disorder.

Note that this designation is based on data from the LEAP2MONO phase 3 study in which patients receiving venglustat demonstrated statistically significant improvements in neurological symptoms measured by a global test score that included assessments for ataxia and cognition compared with patients receiving the enzyme replacement therapy, imiglucerase. In the study, venglustat was well tolerated overall with no new safety signals compared with previous studies. The most commonly reported adverse events were headache, nausea, spleen enlargement, and diarrhea.

In addition, accumulation of GSLs in the CNS can result in neurological symptoms, in addition to the systemic manifestations seen in GD1, such as liver and spleen enlargement, anaemia, low platelet counts, and bone disease. Systemic manifestations of GD3 are treated with ERT but there are no approved treatments for the neurological symptoms. Venglustat works by reducing the abnormal accumulation of GSLs. It is designed to cross the blood-brain barrier to target the underlying pathology causing the neurological effects of GD3.

“This regulatory milestone recognizes the significant unmet medical need for people living with type 3 Gaucher disease, particularly those experiencing progressive neurological deterioration,” said Karin Knobe, Global Head of Clinical Development, Rare Diseases at Sanofi. “The positive LEAP2MONO findings are an encouraging step forward in the research and development process, and we will continue collaborating with the FDA to advance this potential treatment option.”

Venglustat was granted fast-track designation from the FDA for its potential use in GD3 as well as orphan designation for GD3 in the US, EU and Japan. Sanofi will pursue global regulatory filings for venglustat in GD3 during 2026.

Furthermore, the FDA Breakthrough Therapy designation is designed to expedite the development and review of medicines in the US that target serious or life-threatening conditions.

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Related Topics and Keywords

Gaucher disease, Sanofi, Sanofi’s venglustat, type 3 Gaucher disease