A Multicenter, Double-Blind, Randomized Safety and Efficacy Study of Two Dose Levels of Taliglucerase Alfa in Pediatric Patients with Gaucher Disease.
Authors: Zimran Ari , Gonzalez-Rodriguez Derlis Emilio , Abrahamov Aya , Elstein Deborah , Heitner Rene , Paz Alona , Brill-Almon Einat , Chertkoff Raul 
Published: October 2019

Abstract
Abstract 2140
In the treatment of Gaucher disease (GD), early intervention with enzyme replacement therapy (ERT) is crucial in the prevention of irreversible pathology in symptomatic children. Taliglucerase alfa is a plant-cell-expressed human beta-glucocerebrosidase ERT recently approved in the United States for the treatment of adult patients with GD.
The purpose of this study was to investigate the safety and efficacy of taliglucerase alfa in pediatric GD patients.
This was a multicenter, double-blind, 12-month study in patients aged 2 to <18 years randomly assigned to taliglucerase alfa 30 or 60 U/kg. The primary efficacy variable was median percent change in hemoglobin concentration from baseline. Secondary variables were the percent change in spleen and liver volumes, platelet count, and chitotriosidase or CCL18. Exploratory endpoints included change in growth and development, bone disease (assessed by dual energy X-ray absorptiometry [DEXA] and occurrence of bone crises) and change in quality of life (QoL). Safety was assessed by adverse events (AEs), clinical laboratory results, echocardiography, and anti-taliglucerase alfa antibodies. After completion of the 12-month study, patients were eligible to enter a 2-year extension.
A total of 11 patients (10 type 1 and 1 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 the percent change from baseline for hemoglobin increased by 13.8% and 15.8%, platelet count increased by 30.9% and 73.7%, liver volume was reduced by 6.3% and 14.0%, spleen volume was reduced by 28.6% and 41.1%, and chitotriosidase activity was reduced by 58% and 66% for the 30 U/kg and 60 U/kg doses, respectively. The majority of the AEs were mild or moderate, 15.1% of the AEs were reported as treatment related and 1 related serious AE was reported (gastroenteritis requiring hospitalization for rehydration; the patient continues on treatment). There were no unexpected AEs and all treatment-related AEs were transient in nature.
Taken together, these results suggest that taliglucerase alfa has the potential to provide an alternative therapy in pediatric patients with GD.

Disclosures:
Zimran: Protalix Biotherapeutics: Consultancy; Protalix Biotherapeutics: stock options, stock options Other; Protalix Biotherapeutics: Scientific Advisory Board, Scientific Advisory Board Other; Genzyme: Research Funding; Shire HGT: Honoraria; Actelion: Honoraria; Pfizer: Honoraria. Gonzalez-Rodriguez:Pfizer: Study Investigator Other. Abrahamov:Pfizer: Study Investigator Other. Elstein:Pfizer: Study Investigator Other. Heitner:Pfizer: Study Investigator Other. Paz:Protalix Biotherapeutics: Employment. Brill-Almon:Protalix Biotherapeutics, Carmiel, Israel: Employment. Chertkoff:Protalix Biotherapeutics, Carmiel, Israel: Employment.