Dr. Pramod Mistry provides an update of the ENGAGE trial, which evaluating Cerdelga (eliglustat) for treatment-naïve patients with type 1 Gaucher disease. Cerdelga is an oral substrate reduction therapy and is approved as a first-line treatment for adults with type 1 Gaucher disease with poor, intermediate, or extensive CYP2D6-metabolizer phenotypes. Its approval was based on the phase 3 ENGAGE trial, which was published in JAMA in 2015.

The ENGAGE trial was a double-blind, randomized, placebo-controlled trial in which 40 adult patients with type 1 Gaucher disease received either Cerdelga or placebo for 39 weeks. The primary endpoint was spleen volume and compared to placebo, treatment with Cerdelga resulted in a greater reduction in spleen volume from baseline to the end of the 39 week study. Cerdelga also showed greater improvement in liver volume, blood platelet count, and red blood cell (hemoglobin) level, compared to placebo.

Gaucher disease is an inherited condition affecting fewer than 10,000 people worldwide. People with Gaucher disease do not have enough of an enzyme, beta-glucosidase (glucocerebrosidase) that breaks down a certain type of fat molecule. As a result, lipid engorged cells (called Gaucher cells) amass in different parts of the body, primarily the spleen, liver and bone marrow. Accumulation of Gaucher cells may cause spleen and liver enlargement, anemia, excessive bleeding and bruising, bone disease and a number of other signs and symptoms. The most common form of Gaucher disease type 1, generally does not affect the brain.

Cerdelga (eliglustat), a novel glucosylceramide analog given orally, was designed to partially inhibit the enzyme glucosylceramide synthase, which results in reduced production of glucosylceramide. Glucosylceramide is the substance that builds up in the cells and tissues of people with Gaucher disease. The concept was initially developed by the late Norman Radin, PhD, from the University of Michigan. In pre-clinical studies, the molecule, developed with James A. Shayman, MD, also from the University of Michigan, showed specificity for glucosylceramide synthase.