Eliglustat maintains long-term clinical stability in patients with Gaucher disease type 1 stabilized on enzyme therapy

Blood. 2017 Apr 27;129(17):2375-2383. doi: 10.1182/blood-2016-12-758409. Epub 2017 Feb 6.

Abstract

In the phase 3 Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease Who Have Reached Therapeutic Goals With Enzyme Replacement Therapy (ENCORE), at 1 year, eliglustat was noninferior to imiglucerase enzyme therapy in maintaining stable platelet counts, hemoglobin concentrations, and spleen and liver volumes. After this primary analysis period, patients entered a long-term extension phase in which all received eliglustat. Duration on eliglustat ranged from 2 to 5 years, depending on timing of enrollment (which spanned 2 years), treatment group to which patients were randomized, and whether they lived in the United States when commercial eliglustat became available. Here we report long-term safety and efficacy of eliglustat for 157 patients who received eliglustat in the ENCORE trial; data are available for 46 patients who received eliglustat for 4 years. Mean hemoglobin concentration, platelet count, and spleen and liver volumes remained stable for up to 4 years. Year to year, all 4 measures remained collectively stable (composite end point relative to baseline values) in ≥85% of patients as well as individually in ≥92%. Mean bone mineral density z scores (lumbar spine and femur) remained stable and were maintained in the healthy reference range throughout. Eliglustat was well tolerated over 4 years; 4 (2.5%) patients withdrew because of adverse events that were considered related to the study drug. No new or long-term safety concerns were identified. Clinical stability assessed by composite and individual measures was maintained in adults with Gaucher disease type 1 treated with eliglustat who remained in the ENCORE trial for up to 4 years. This trial was registered at www.clinicaltrials.gov as #NCT00943111.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Bone Density / drug effects
  • Enzyme Inhibitors / therapeutic use*
  • Enzyme Replacement Therapy*
  • Female
  • Femur / drug effects
  • Femur / enzymology
  • Gaucher Disease / drug therapy*
  • Gaucher Disease / enzymology
  • Gaucher Disease / physiopathology
  • Glucosylceramidase / therapeutic use*
  • Humans
  • Liver / drug effects
  • Liver / enzymology
  • Lumbar Vertebrae / drug effects
  • Lumbar Vertebrae / enzymology
  • Male
  • Middle Aged
  • Platelet Count
  • Pyrrolidines / therapeutic use*
  • Recombinant Proteins / therapeutic use*
  • Spleen / drug effects
  • Spleen / enzymology

Substances

  • Enzyme Inhibitors
  • Pyrrolidines
  • Recombinant Proteins
  • eliglustat
  • Glucosylceramidase
  • imiglucerase

Associated data

  • ClinicalTrials.gov/NCT00943111