FDA grants priority review to treatment aimed at type 3 Gaucher
Sanofi’s venglustat could be first U.S. treatment for neurological symptoms
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The U.S. Food and Drug Administration (FDA) has granted priority review to an application for venglustat, an experimental substrate reduction therapy (SRT) that Sanofi is developing for Gaucher disease type 3. The FDA grants priority review to applications for therapies that may offer significant improvements for serious conditions. The status shortens the FDA’s target review timeline to about six months from the standard 10 months. Sanofi expects a decision by Nov. 25, according to a company press release.
Venglustat is under review in the European Union for the same indication, and Sanofi said it plans to pursue additional global filings this year.
Gaucher disease is caused by mutations that interfere with the body’s ability to produce glucocerebrosidase (GCase), an enzyme responsible for breaking down certain fatty substances. Without enough working GCase, these fatty molecules accumulate to harmful levels in cells, leading to Gaucher symptoms that may include blood abnormalities, enlarged organs, and bone disease.
Gaucher type 3 is a relatively rare form of the disease marked by neurological symptoms that typically manifest in late childhood or adulthood and progress slowly. This contrasts with the more common Gaucher disease type 1, which does not cause neurological symptoms, and Gaucher disease type 2, a severe form of the disease marked by rapidly progressive neurological symptoms that usually lead to death in early childhood. Venglustat would be the first treatment to address both neurological and non-neurological symptoms in people with Gaucher disease type 3.
Brain-reaching potential
Sanofi’s Cerezyme (imiglucerase) is the only approved therapy for Gaucher disease type 3 in the U.S. Given through intravenous (into-the-vein) infusions, Cerezyme is an enzyme replacement therapy (ERT) designed to provide the body with a functional version of GCase, helping cells clear the harmful fatty buildup that drive disease symptoms.
However, ERTs have a limited ability to reach the brain and cannot help clear the fatty buildup that drives the neurological symptoms of Gaucher. For this reason, Cerezyme is specifically approved to help manage the disease’s non-neurological complications.
Venglustat is an oral SRT that blocks the activity of glucosylceramide synthase, a protein that helps produce the fatty molecules that accumulate in Gaucher. By shutting down their production, venglustat aims to limit the toxic buildup of these fatty molecules.
Because venglustat can reach the brain, it has the potential to address both neurological and non-neurological manifestations of the disease.
Venglustat’s application was supported by data from the Phase 3 clinical trial LEAP2MONO (NCT05222906), which enrolled 43 children and adults with Gaucher type 3 who were clinically stable on long-term ERT before enrollment. Participants were randomly assigned to receive Cerezyme or a daily venglustat tablet for one year.
LEAP2MONO met its main goal, with venglustat significantly outperforming Cerezyme at improving two measures of neurological function: an assessment of cognition and a measure of ataxia, a motor coordination problem.
Venglustat was also as effective as Cerezyme at controlling key non-neurological Gaucher symptoms, leading to reductions in spleen and liver size and increases in levels of hemoglobin, the protein that helps red blood cells carry oxygen.
The therapy was well tolerated, with no new safety signals. Common side effects reported more often with venglustat than Cerezyme included nausea, diarrhea, and spleen enlargement.
The FDA previously granted the treatment breakthrough therapy and fast track designations for type 3 Gaucher. These statuses are intended to speed the development and review of therapies for serious conditions. The therapy also holds orphan drug designation — a status intended to encourage the development of treatments for rare diseases through regulatory and financial incentives — for Gaucher type 3 in the U.S., European Union, and Japan,
