A multicenter, double-blind, randomized safety and efficacy study of two dose levels of taliglucerase alfa in pediatric patients with Gaucher disease

Abstract

In the treatment of Gaucher disease (GD), early intervention with enzyme replacement therapy (ERT) is crucial in prevention of irreversible pathology. Taliglucerase alfa is a plant cell–expressed beta-glucocerebrosidase ERT that is approved in the USA, Israel, and Uruguay for treatment of GD in adults. The aim of this multicenter, double-blind, dose-ranging (30 and 60 U/kg), 12-month study was to investigate the safety and efficacy of taliglucerase alfa in pediatric GD patients aged 2 to <18 years. Primary efficacy variable: median percent change in hemoglobin concentration from baseline. Secondary variables: percent changes in spleen/liver volumes, platelet counts, and chitotriosidase activity. After completion of the 12-month study, patients were eligible to enter a 2-year extension. Eleven patients (nine, type 1; two, type 3) were randomized to taliglucerase alfa 30 or 60 U/kg. Progressive improvement was demonstrated in hemoglobin, spleen volume, liver volume, platelet count, and chitotriosidase activity. At 12 months, composite analysis of both dose groups revealed that mean hemoglobin and platelets were increased by 14.7% and 50.3%, respectively, from baseline, and absolute spleen and liver volumes were reduced 34.2% and 9.8%, respectively, from baseline. The majority (96.2%) of adverse events (AEs) were mild or moderate, 15.1% were reported as treatment related, and one related serious AE was reported (patient continues on treatment). There were no unexpected AEs and all treatment-related AEs were transient in nature. Taken together, as previously seen for adult patients with GD, data suggest that taliglucerase alfa has the potential to provide an alternative therapy in pediatric patients.