Eliglustat

Eliglustat is a glucosylceramide synthase inhibitor used for the long-term treatment of type 1 Gaucher disease. Gaucher disease is a rare genetic disorder characterized by the deficiency of acid β-glucosidase, an enzyme that converts glucosylceramide into glucose and ceramide. In patients with Gaucher disease, the accumulation of glucosylceramide leads to the formation of Gaucher cells that infiltrate the liver, spleen, bone marrow and other organs. This leads to complications such as anemia and thrombocytopenia. By inhibiting glucosylceramide synthase, eliglustat reduces the accumulation of glucosylceramide. Eliglustat is mainly metabolized by CYP2D6. Patients selected for eliglustat treatment undergo an FDA-cleared genotyping test to establish if they are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs). The results of this test dictate eliglustat dosing recommendations for each type of patient. There are no dosing recommendations for CYP2D6 ultra-rapid or indeterminate metabolizers. Eliglustat was approved by the FDA in August 2014 as an oral substrate reduction therapy for the first-line treatment of type 1 Gaucher disease. Enzyme replacement continues to be the standard of care for the treatment of type 1 Gaucher disease (imiglucerase, velaglucerase alfa, taliglucerase alfa); however, oral substrate reduction therapies with favourable safety profiles, such as eliglustat, represent a treatment alternative.