Taliglucerase alfa: safety and efficacy across 6 clinical studies in adults and children with Gaucher disease

Ari Zimran,Gregory M Pastores,Michael Wajnrajch,Betina Hernandez

doi:10.1186/s13023-018-0776-8

Abstract

Taliglucerase alfa is an enzyme replacement therapy (ERT) approved for treatment of adult and paediatric patients with Type 1 Gaucher disease (GD) in several countries and the first plant cell–expressed recombinant therapeutic protein approved by the US Food and Drug Administration for humans. Here, we review the findings across six key taliglucerase alfa clinical studies. A total of 33 treatment-naïve adult patients were randomized to taliglucerase alfa 30 U/kg or 60 U/kg in a 9-month, multicentre, randomized, double-blind, parallel-group, dose-comparison pivotal study, after which eligible patients continued into two consecutive extension studies; 17 treatment-naïve adult patients completed 5 total years of treatment with taliglucerase alfa. In the only ERT study focused on exclusively paediatric patients with GD, 11 treatment-naïve children were randomized to taliglucerase alfa 30 U/kg or 60 U/kg in a 12-month, multicentre, double-blind study; nine completed 3 total years of treatment in a dedicated paediatric extension study. The effect of switching patients from imiglucerase to taliglucerase alfa was also investigated in a separate 9-month study that included 26 adults and five children; 10 adults completed a total of 3 years and two children completed a total of 2.75 years of taliglucerase alfa treatment in the extension studies. All studies evaluated safety and spleen volume, liver volume, platelet count, haemoglobin concentration, and biomarkers as measures of efficacy. Detailed results from baseline through the end of these studies are presented. Taliglucerase alfa was well tolerated, and adverse events were generally mild/moderate in severity and transient. Treatment with taliglucerase alfa resulted in improvements (treatment-naïve patients) or stability (patients switched from imiglucerase) in visceral, haematologic, and biomarker parameters. Together, this comprehensive data set supports the treatment of adult and paediatric patients with GD who are naïve to ERT or who have previously been treated with imiglucerase.

Highlights

Gaucher disease (GD) is a rare lysosomal storage disorder caused by autosomal recessive mutations in the gene encoding β-glucocerebrosidase, a lysosomal enzyme required for the degradation of the glycolipid, glucocerebroside [1]
The purpose of this review is to provide an overview of the results from the phase 3 clinical studies of taliglucerase alfa in adults and children with GD
Growth inhibition and pubertal delay have been observed in children with GD [23–28], and exploratory analyses of growth and development in paediatric patients in the phase 3 taliglucerase alfa studies trended toward improvement in height and weight, progression of pubertal status, and absence of bone crises [20]

Summary

Introduction

Gaucher disease (GD) is a rare lysosomal storage disorder caused by autosomal recessive mutations in the gene encoding β-glucocerebrosidase, a lysosomal enzyme required for the degradation of the glycolipid, glucocerebroside [1]. In the United States and many countries in the European Union, three ERTs have been approved for the Zimran et al Orphanet Journal of Rare Diseases (2018) 13:36 treatment of Type 1 GD: taliglucerase alfa, velaglucerase alfa, and imiglucerase. All three ERTs are recombinant active forms of β-glucocerebrosidase and are administered by intravenous infusion [5–8]. Both velaglucerase alfa and imiglucerase are produced in mammalian cellbased expression systems that require glycosylation modifications during production to expose the appropriate mannose residues needed for efficient cellular uptake of the recombinant enzymes, adding cost and additional steps to the production processes [4, 6, 7, 9–11]. Mammalian cell-based expression systems have been vulnerable to the risk of supply shortage, such as the viral contamination of a bioreactor that prompted the temporary suspension of imiglucerase manufacturing [12]

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