title: Stability is maintained in adults with Gaucher disease type 1 switched from velaglucerase alfa to eliglustat or imiglucerase: A sub-analysis of the eliglustat ENCORE trial.
abstract: Gaucher disease type 1 is an autosomal recessive disorder caused by deficient activity of the lysosomal enzyme acid β-glucosidase resulting in accumulation of glucosylceramide and clinical manifestations of anemia, thrombocytopenia, hepatosplenomegaly, and skeletal disease. The historic standard of care is intravenous recombinant enzyme therapy with imiglucerase. Eliglustat, an oral substrate reduction therapy, is a first-line treatment for adults with Gaucher disease type 1 who have a compatible CYP2D6-metabolizer phenotype (≈ 95% of patients). The 12-month ENCORE trial (NCT00943111) found eliglustat non-inferior to imiglucerase in maintaining stability in adult Gaucher patients previously stabilized after ≥ 3 years of enzyme therapy (imiglucerase or velaglucerase alfa). This post-hoc analysis examined safety and efficacy in the 30 ENCORE patients who were receiving velaglucerase alfa at study entry and were randomized to eliglustat (n = 22) or imiglucerase (n = 8). Efficacy and safety in velaglucerase alfa-transitioned patients were consistent with the full ENCORE trial population; 90% of patients switched to eliglustat and 88% of patients switched to imiglucerase met the composite endpoint (stable hemoglobin concentration, platelet count, spleen volume, and liver volume). Clinical stability was maintained for 12 months in Gaucher disease type 1 patients in the ENCORE trial who switched from velaglucerase alfa to either eliglustat or imiglucerase.
authors.affiliation: Sanofi Genzyme, Cambridge, MA, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pleat
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Cox
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: T Andrew
authors.initials: TA
authors.lastname: Burrow
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), IISAragón, Zaragoza, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Giraldo
authors.affiliation: Lysosomal Disorders Research and Treatment Unit, Center for Clinical Trials, O&O Alpan, LLC, Fairfax, VA, USA.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Goker-Alpan
authors.affiliation: Cedars-Sinai/Tower Hematology Oncology, Beverly Hills, CA, USA.
authors.forename: Barry E
authors.initials: BE
authors.lastname: Rosenbloom
authors.affiliation: Sanofi Genzyme, Cambridge, MA, USA.
authors.forename: Laura R
authors.initials: LR
authors.lastname: Croal
authors.affiliation: Sanofi Genzyme, Cambridge, MA, USA.
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Underhill
authors.affiliation: Sanofi Genzyme, Cambridge, MA, USA.
authors.forename: Sebastiaan J M
authors.initials: SJ
authors.lastname: Gaemers
authors.affiliation: Sanofi Genzyme, Cambridge, MA, USA.
authors.forename: M Judith
authors.initials: MJ
authors.lastname: Peterschmitt
keywords: Composite endpoint; Eliglustat; Gaucher disease type 1; Imiglucerase; Non-inferiority trial; Velaglucerase alfa