| アブストラクト | Eliglustat, an oral substrate reduction therapy, is a first-line treatment for adults with Gaucher disease type 1 (GD1) who are poor, intermediate, or extensive CYP2D6 metabolizers (>90% of patients). In the primary analysis of the Phase 3 ENGAGE trial (NCT00891202), eliglustat treatment for 9 months resulted in significant reductions in spleen and liver volumes and increases in hemoglobin concentration and platelet count compared with placebo. We report 18-month outcomes of patients who entered the trial extension period, in which all patients received eliglustat. Of 40 trial patients, 39 entered the extension period, and 38 completed 18 months. Absolute values and percent change over time were determined for spleen and liver volume, hemoglobin concentration, platelet count, bone mineral density, bone marrow burden, and Gaucher disease biomarkers. For patients randomized to eliglustat in the double-blind period, continuing treatment with eliglustat for 9 more months resulted in incremental improvement of all disease parameters. For patients randomized to placebo in the double-blind period, eliglustat treatment during the 9-month, open-label period resulted in significant decrease of spleen and liver volumes and significant increase of hemoglobin and platelets, with a similar rate of change to patients who had received eliglustat in the double-blind period. Eliglustat treatment was also associated with improvement in bone marrow burden score, bone mineral density, and established biomarkers of Gaucher disease, including reduction of the bioactive lipid, glucosylsphingosine. These findings underscore the efficacy of eliglustat in treatment-naive patients. Eliglustat was well-tolerated, and there were no new safety concerns with longer-term exposure. |
|---|
| 投稿者 | Mistry, Pramod K; Lukina, Elena; Ben Turkia, Hadhami; Shankar, Suma P; Baris, Hagit; Ghosn, Marwan; Mehta, Atul; Packman, Seymour; Pastores, Gregory; Petakov, Milan; Assouline, Sarit; Balwani, Manisha; Danda, Sumita; Hadjiev, Evgueniy; Ortega, Andres; Gaemers, Sebastiaan J M; Tayag, Regina; Peterschmitt, M Judith |
|---|
| 組織名 | Department of Internal Medicine and Pediatrics, Yale University School of;Medicine, New Haven, CT, USA.;Department of Orphan Diseases, National Research Center for Hematology, Moscow,;Russia.;Department of Pediatrics, Hopital La Rabta, Tunis, Tunisia.;Department of Human Genetics, Emory University School of Medicine, Atlanta, GA,;USA.;Raphael Recanati Genetic Institute, Rabin Medical Center, Petach Tikvah, Israel.;Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.;The Genetics Institute, Rambam Health Care Campus and The Ruth and Bruce;Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa,;Israel.;Department of Hematology-Oncology, Hotel-Dieu de France University Hospital,;Beirut, Lebanon.;Department of Haematology, The Royal Free Hospital, University College, London,;UK.;Department of Pediatrics, UCSF School of Medicine, San Francisco, CA, USA.;Department of Neurology and Pediatrics, New York University School of Medicine,;New York, NY, USA.;Department of Neuroendocrinology, Clinical Center of Serbia, Belgrade University;Medical School, Serbia.;Department of Medicine, Division of Hematology, Jewish General Hospital,;Montreal, Quebec, Canada.;Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mt.;Sinai Hospital, New York, NY, USA.;Department of Medical Genetics, Christian Medical College, Vellore, Tamil Nadu,;India.;Medical University - Sofia, Faculty of Medicine, Department of Internal diseases,;UMHAT "Alexandrovska"- Clinic of Hematology, Sofia, Bulgaria.;OCA Hospital, Monterrey, Mexico.;Global Pharmacovigilance, Sanofi Genzyme, Naarden, The Netherlands.;Prometrika, Cambridge, MA, USA.;Rare Diseases Clinical Development, Sanofi Genzyme, Cambridge, MA, USA. |
|---|
