Velaglucerase alfa, a human recombinant glucocerebrosidase enzyme replacement therapy for type 1 Gaucher disease.

Gaucher disease (GD) is caused by a deficiency of the lysosomal enzyme glucocerebrosidase, which results in the accumulation of its substrate, glucocerebroside, in macrophages. This excess in lipid storage within macrophages (subsequently recognized as Gaucher cells) leads to the development of disease, which presents clinical features including anemia, thrombocytopenia and hepatosplenomegaly, and can also lead to the development of neurological problems or bone disease. Velaglucerase alfa is a gene-activated human recombinant glucocerebrosidase being developed by Shire Human Genetic Therapies Inc as an enzyme replacement therapy for type 1 GD. In vitro, velaglucerase alfa was internalized by human macrophages more rapidly than imiglucerase, which has been the sole standard of care for GD for over 15 years. Clinical trials in patients with GD demonstrated that the safety and efficacy of velaglucerase alfa appeared to be comparable with historical imiglucerase data, although head-to-head data were unavailable. Recent problems with the production of imiglucerase led to the unanticipated introduction of velaglucerase alfa to patients with GD through a pre-approval expanded access protocol. Whether this will prove beneficial, in terms of uptake and prescribing of the enzyme, remains to be seen in a market dominated by imiglucerase.