- Sanofi has stopped clinical testing of a top drug prospect in a rare kidney disease after results showed treatment did not meaningfully prevent the growth of cysts, a setback for the French pharmaceutical company's development plans.
- An independent analysis found the drug, called venglustat, did not reduce the rate of growth in total kidney volume versus placebo in a Phase 2/3 study, Sanofi said in a statement Tuesday. The trial tested venglustat as a treatment for autosomal dominant polycystic kidney disease, a genetic condition that can lead to kidney failure.
- Venglustat is one of Sanofi's priority drug candidates, and the company has been developing it for several rare diseases affecting cellular metabolism, like Gaucher and Fabry. But Sanofi also sought to prove venglustat beyond these so-called lysosomal storage disorders and into more common conditions like ADPKD and Parkinson's disease. A Phase 2 study in Parkinson's was stopped in January.
Venglustat is one of half a dozen experimental drugs hand-picked by Sanofi executives as top research priorities under CEO Paul Hudson's efforts to revitalize the pharma company's pipeline.
While Sanofi continues to test venglustat in several late-stage trials for lysosomal storage disorders, Tuesday's announcement appears to close off a substantial opportunity for the drug. Gaucher Type 3, GM2 gangliosidosis and Fabry — the three lysosomal storage disorders Sanofi aims to treat with venglustat — affect between roughly 100 and 3,000 patients in the U.S.
By comparison, there are about 140,000 patients diagnosed with ADPKD, according to Sanofi.
Sanofi didn't disclose any specific results Tuesday. Biomarker data from the study confirmed treatment with venglustat reduced the targeted fat that accumulates in specific cells. But that effect didn't appear to translate into less cyst growth, which suggests elevated lipid levels may not be the primary driver of disease progression in ADPKD, Sanofi said.
"This outcome is not what we hoped for, especially for these patients," said John Reed, Sanofi's head of R&D, in a statement. "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."
Earlier this year, venglustat also missed its goal in a Phase 2 study of Parkinson's disease patients who have mutations in a gene known as GBA.
In both cases, Sanofi said the safety profile of venglustat was consistent with previous results, indicating there were no side effect concerns that would preclude further study in lysosomal storage disorders.
Success in the ADPKD trial would have allowed Sanofi to submit venglustat next year. Should current timelines for testing in Gaucher, Fabry and GM2 hold, the drugmaker doesn't anticipate submitting for approval until 2023 at the earliest.
Sanofi, through its Genzyme division, is one of the top manufacturers of treatments for lysosomal storage disorders, marketing the drugs Cerdelga, Cerezyme, Myozyme and Fabrazyme. Also in its pipeline are olipudase alfa, for acid sphingomyelinase deficiency, and avalglucosidase alfa, for Pompe. An FDA decision on the latter was recently delayed by three months, to Aug. 18.