Jennifer Ibrahim, Head of North America, Rare Disease Medical Affairs at Sanofi, discusses the Breakthrough Therapy designation of venglustat for the treatment of neurological manifestations in Gaucher disease type 3 (GD3).
Gaucher disease refers to a group of inherited metabolic diseases in which harmful amounts of lipids accumulate in the body. It is caused by genetic changes in the GBA gene that lead to reduced levels of glucocerebrosidase. Signs and symptoms vary widely among affected individuals and may include skeletal disorders, hepatosplenomegaly, liver malfunction, anemia, low platelet counts, bone problems, and neurological problems. There are three main forms of the disease: GD1, characterized by lack of central nervous system involvement; GD2, marked by rapid neurological decline and severe neurocognitive symptoms; and GD3, marked by slower and more variable progression and symptom severity.
Venglustat is a novel, investigational oral glucosylceramide synthase inhibitor (GCSi) that reduces abnormal accumulation of glycosphingolipids. It is designed to cross the blood-brain barrier to target the underlying pathology causing the neurological effects of GD3.
The Breakthrough designation is based on data from the LEAP2MONO phase 3 double-blind, double-dummy, active-comparator, two-arm study (NCT05222906). Patients receiving venglustat demonstrated statistically significant improvements in neurological symptoms measured by a global test score that included assessments for ataxia (mSARA) and cognition (RBANS) compared with patients receiving the enzyme replacement therapy (ERT), imiglucerase. In the study, venglustat was well tolerated overall with no new safety signals compared with previous studies. The most commonly reported adverse events were headache, nausea, spleen enlargement, and diarrhea.
FDA Breakthrough Therapy designation is designed to expedite the development and review of medicines in the US that target serious or life-threatening conditions. Medicines qualifying for this designation must show preliminary clinical evidence that the drug may demonstrate substantial improvement on clinically significant endpoints over available medicines.
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To learn more about GD3 and other rare lysosomal storage disorders, visit https://checkrare.com/diseases/lysosomal-storage-disorders/
