Sanofi’s investigational rare disease drug venglustat delivered a Phase 3 win in neurological Gaucher disease but failed in a separate late-stage Fabry study, underscoring a mixed path for the once high-profile therapy.
Type 3 Gaucher disease is a rare inherited lysosomal storage disorder that affects the brain. Patients develop progressive problems with motor coordination and cognition. Enzyme replacement therapies can manage systemic symptoms but cannot cross the blood–brain barrier. As a result, neurological disease remains largely untreated.
Venglustat is an oral glucosylceramide synthase inhibitor that reduces the buildup of lipid substrates linked to disease progression. Unlike enzyme replacement therapy, it reaches the central nervous system. That feature positions the drug as a potential option for neurological symptoms.
Sanofi said its Phase 3 LEAP2MONO trial met the primary endpoint after 52 weeks of treatment. The study enrolled 43 patients with type 3 Gaucher disease and compared venglustat with standard enzyme replacement therapy. Patients treated with venglustat showed improvements in neurological symptoms. Investigators measured outcomes using the Scale for the Assessment and Rating of Ataxia and the Repeatable Battery for the Assessment of Neuropsychological Status, which assess motor coordination and cognition.
Venglustat also matched enzyme replacement therapy on key secondary measures. These included spleen volume, liver volume and hemoglobin levels. Sanofi reported a generally manageable safety profile. The most common adverse events included gastrointestinal symptoms, headache and spleen enlargement. The company plans to present detailed data this week at the WORLD Symposium in San Diego and aims to advance the program toward regulatory submission.
The drug fell short in Fabry disease. Sanofi said the Phase 3 PERIDOT trial did not show a significant improvement in pain versus placebo in 122 patients. Pain scores declined in both study arms, limiting the drug’s ability to separate from placebo.
Fabry disease is another lysosomal storage disorder that primarily affects the heart, kidneys and peripheral nervous system. Sanofi will continue evaluating venglustat in Fabry through the ongoing Phase 3 CARAT trial. That study focuses on cardiac outcomes, including left ventricular mass index.
The mixed results narrow but clarify venglustat’s future. After prior failures in Parkinson’s disease and autosomal dominant polycystic kidney disease, the Gaucher win stands out. The data support a focused opportunity in a high-unmet-need neurological population and position venglustat as a potential first oral therapy for brain involvement in type 3 Gaucher disease.
