Sanofi Halts Pivotal Phase II/III Trial of Venglustat in Autosomal Dominant Polycystic Kidney Disease Due to Futility

Compiled & Translated by | river

Sanofi announced on June 1 that it is discontinuing a pivotal Phase II/III kidney disease trial for venglustat, a novel molecule designed to slow disease progression by inhibiting the abnormal accumulation of glycosphingolipids.

Notably, as early as February, Sanofi reported another setback for venglustat in a Phase II clinical trial for Parkinson’s disease. The study, which included patients with Parkinson’s disease and GBA mutations, failed to meet its primary endpoint, limiting the company’s options for further research into neurological disease treatments.

Regarding this suspension, Sanofi stated that the Phase II/III trial of venglustat for the treatment of autosomal dominant polycystic kidney disease (ADPKD) has been discontinued because it “did not meet the futility criteria.” The determination of these criteria was based on an independent analysis of the annual rate of change in total kidney volume in patients receiving venglustat versus placebo. The independent analysis revealed a trend indicating that treatment with the molecule did not result in a clinically meaningful reduction in the rate of total kidney volume growth, which represented the primary endpoint for the first stage of the study.

The study of venglustat in patients with autosomal dominant polycystic kidney disease (ADPKD) was an attempt to explore novel biological roles of glycosphingolipids beyond their known functions in lysosomal storage diseases (LSDs). However, interim analysis indicated that the venglustat-associated reduction in glycosphingolipids may not have a significant preventive effect on renal cyst growth.

Sanofi reported that the safety profile of venglustat was consistent with findings from previous studies involving over 500 patients treated for up to four years. Additionally, biomarker data from the latest study demonstrated that this novel molecule clearly and effectively inhibited the glycosphingolipid pathway by reducing lipid GL-1.

Dr. John Reed, Global Head of Research and Development at Sanofi, stated that the venglustat development program was initiated with a commitment to a potential breakthrough therapy aimed at addressing the unmet needs of patients with lysosomal storage disorders. Researchers found that the venglustat-associated outcomes in autosomal dominant polycystic kidney disease were "not what we had hoped for," and studies conducted by the investigative team demonstrated that "modulating the glycosphingolipid pathway is insufficient to restore kidney function in adults affected by this disease."

To date, Sanofi has completed trials of venglustat for various lysosomal storage diseases (LSDs) associated with genetic abnormalities. These conditions include Fabry disease, GM2 gangliosidosis, and Gaucher disease type 3. In these cases, certain therapies aim to clear abnormally accumulated glycosphingolipids. Clinical studies have validated these therapies in Gaucher disease and Fabry disease. In this context, venglustat is specifically used as a substrate reduction therapy.

Reference: Sanofi Halts Kidney Disease Program Studying Venglustat Drug