Sanofi's First-in-Class Candidate Venglustat Granted Clinical Trial Approval in China for Type 3 Gaucher Disease with Neurological Involvement

On October 28, the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) publicly announced that venglustat, a Class 1 new drug jointly submitted by Sanofi and its subsidiary Genzyme, has received implied approval for two clinical trials. The drug is intended for the treatment of adolescent and adult patients aged ≥12 years with Gaucher disease who are receiving imiglucerase injection therapy and exhibit neurological involvement. According to public information, venglustat has the potential to become a “first-in-class” therapy for neuropathic Type 3 Gaucher disease.

Source: CDE Official Website

Venglustat is an investigational oral therapy capable of crossing the blood-brain barrier, designed to inhibit the abnormal accumulation of glucosylceramide (GL-1), a substance involved in glycosphingolipid production. By inhibiting glucosylceramide synthase activity, venglustat can treat various rare diseases caused by genetic mutations in the glycosphingolipid metabolic pathway, including: Gaucher disease type 3, GBA-associated Parkinson’s disease, Fabry disease, and autosomal dominant polycystic kidney disease (ADPKD).

Venglustat has been approved for clinical trials in China, with the indication being Gaucher disease. This is a genetic disorder that has been included in China’s "First Batch of Rare Diseases Catalog." The accumulation of glucosylceramide in cells and organs leads to symptoms such as easy bruising and splenomegaly. Gaucher disease is caused by mutations in the GBA gene, which significantly reduce or eliminate the activity of β-glucocerebrosidase. Without sufficient levels of this enzyme, glucocerebroside and related substances can accumulate to toxic levels within cells.

According to public data, venglustat has demonstrated efficacy in Phase 2 clinical trials for the treatment of Type 3 Gaucher disease and is poised to become a “first-in-class” therapy for neuropathic Type 3 Gaucher disease. Currently, Phase 2/3 clinical trials of this product for Gaucher disease are ongoing. Sanofi expects to submit a registration application for this indication in the first half of 2023. Furthermore, clinical development of this product for autosomal dominant polycystic kidney disease (ADPKD) has advanced to Phase 3.

▲Venglustat has demonstrated efficacy in clinical studies for Type 3 Gaucher disease (Image source: Reference [2])

It is worth noting that Sanofi had previously launched imiglucerase for injection (Cerezyme) in China for the treatment of Gaucher disease. This medication is a synthetic analog of beta-glucocerebrosidase produced through recombinant DNA technology, designed to replace the deficient beta-glucocerebrosidase in patients with Gaucher disease.

In addition, the company’s first-line treatment for Gaucher disease, eliglustat, has also submitted a marketing application in China and been included in the priority review process. It is intended for the long-term treatment of adult patients with type 1 Gaucher disease. This medication is a potent and highly specific ceramide analogue inhibitor that reduces the production of glucosylceramide by targeting glucosylceramide synthase.

References:

[1] Center for Drug Evaluation (CDE), National Medical Products Administration of China. Retrieved Oct 29, 2020, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=21#

[2]R&D Investor Event. Retrieved Jun 23，2020, from https://www.sanofi.com/-/media/Project/One-Sanofi-Web/Websites/Global/Sanofi-COM/Home/common/docs/investors/20200623_RD_Day_Presentation.pdf?la=en&hash=9D46A817C3DFACF27113ED8DD23652CE

Source: Medical Horizon

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