Sanofi's venglustat fails another trial, ending pursuit of kidney disease

Sanofi has stopped a pivotal clinical trial of venglustat in autosomal dominant polycystic kidney disease (ADPKD) for futility. The setback comes months after venglustat failed a phase 2 Parkinson’s disease trial but still leaves Sanofi with shots on goal.

Analysis of interim data from the phase 2/3 study found venglustat didn’t meaningfully reduce the total kidney volume growth rate in ADPKD patients over placebo. The lack of impact on the primary endpoint happened despite biomarker data linking venglustat to reductions in the lipid GL-1. Sanofi sees the data as evidence that the glycosphingolipid (GSL) inhibitor works as intended but is unable to cut kidney volume growth because other pathways are involved in the progression of ADPKD.

“This outcome is not what we hoped for, especially for these patients. However, our research has furthered the scientific understanding of ADPKD by demonstrating that modulating the GSL pathway is insufficient to restore kidney function in adults affected by this disease,” John Reed, M.D., Ph.D., global head of research and development at Sanofi, said in a statement.

Sanofi responded to the failure by halting its ADPKD clinical program. The setback means Sanofi has lost two big opportunities for venglustat, a drug it has called a “pipeline in a pill,” in quick succession.

The role of GSLs is established in lysosomal storage diseases, leading Sanofi to develop venglustat for use in Gaucher disease type 3, Fabry disease and GM2 gangliosidosis. At the same time, Sanofi saw opportunities to use venglustat in the treatment of far more common diseases as it acts early in the signaling cascade. 

Animal model data and other evidence persuaded Sanofi venglustat could work in ADPKD, a disease that affects around 140,000 patients in the U.S. Sanofi also targeted a 78,000-patient subpopulation of Parkinson’s patients. The failure of venglustat in those populations leaves Sanofi to pursue the use of the drug in orphan lysosomal storage diseases that affect far fewer people.