Genotype-based treatment approved for type 1 Gaucher disease.

Abstract

FDA and Sanofi on August 19 announced the approval of eliglustat, or Cerdelga, for the long-term treatment of adults with type 1 Gaucher disease who have a certain drug-metabolizing-enzyme genotype. Eliglustat, a glucosylceramide analog, was designed to partially inhibit the enzyme that synthesizes glucocerebroside, the company said. Patients with Gaucher disease do not adequately catabolize glucocerebroside, which is a lipid molecule in the cell membrane of the brain, nervous tissue, and other tissues. Insufficient activity by the enzyme responsible for breaking down glucocerebroside, FDA said, causes fatty materials to accumulate in the spleen, liver, and bone marrow. Patients can have spleen and liver enlargement, anemia, low blood platelet counts, and bone problems. The labeling for eliglustat instructs clinicians to select patients with type 1 Gaucher disease for treatment with the drug on the basis of their genotype for cytochrome P-450 (CYP) isoenzyme 2D6. Eliglustat is a substrate of CYP2D6. The drug’s labeling recommends dosages for patients who are extensive, intermediate, or poor metabolizers of CYP2D6 substrates but not dosages for ultrarapid metabolizers or patients whose CYP2D6 genotype cannot be determined.