Safety and efficacy of velaglucerase alfa replacement therapy for patients with type 1 Gaucher disease

Abstract

Gaucher disease is a multisystem disorder caused by deficiency of β-glucocerebrosidase. Exogenously delivered enzyme replacement therapy (ERT) is currently standard of care. Since 1994, intravenously delivered recombinant ERT with imiglucerase (Cerezyme; Genzyme Corporation, Cambridge, MA, USA) improves hematological, visceral and skeletal features of Gaucher disease at dosages of 15–60 units/kg bodyweight/infusion, administered every other week (EOW). Velaglucerase alfa (VPRIV^®; Shire HGT, MA, USA) is a human wild-type-sequenced ERT produced in human cell lines using proprietary Gene-Activation^® technology (Shire HGT). This article describes the results of a Phase I/II seminal trial in treatment-naive non-neuronopathic patients (including stepwise dose reduction to 30 units/kg/EOW) and three Phase III trials (two doses: 45 or 60 units/kg/EOW; switch-over from imiglucerase at identical dose; head-to-head with imiglucerase, 60 units/kg/EOW) and Phase III extension trial. Velaglucerase alfa was approved in 2010 in many countries; based on clinical trial experience, it is safe and effective in treatment-naive and switch-over patients, children and adults, splenectomized patients and those with an intact spleen.

Keywords::

• enzyme replacement therapy
• Gaucher disease
• glucocerebrosidase
• imiglucerase
• orphan drugs
• taliglucerase alfa
• velaglucerase alfa

Financial & competing interests disclosure

Shire HGT was given the opportunity to review the manuscript for scientific accuracy, but the conclusions and opinions expressed remain those of the authors. D Elstein has received consultancy fees from Shire Human Genetic Therapies during these clinical trials and currently receives honoraria and travel stipends to present trial results at professional meetings. A Zimran has received consulting fees from Shire Human Genetic Therapies during these clinical trials and currently receives honoraria and travel stipends; receives consulting fees and has options in Protalix Therapeutics and is a member of its Scientific Advisory Board and receives support from Genzyme Corporation for participation in the ICGG registry. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.