Velaglucerase alfa: a new option for Gaucher disease treatment.

Type 1 Gaucher disease (GD) results from inherited β-glucocerebrosidase gene mutations, leading to anemia, thrombocytopenia, splenomegaly, hepatomegaly and skeletal disease. Velaglucerase alfa is a β-glucocerebrosidase produced by gene activation in a human cell line, and indicated for type 1 GD. A phase I/II clinical trial (TKT025; N = 12), its ongoing extension (TKT025EXT) and three phase III trials (total N = 82), showed that velaglucerase alfa is generally well tolerated in adult and pediatric patients. Many disease-related parameters improved significantly in two phase III trials in treatment-naïve patients, and were successfully maintained in imiglucerase-experienced patients in a phase II/III switch study. Ten adults in TKT025EXT sustained improvements through 5 years, including bone mineral density. Comparison with imiglucerase shows that velaglucerase alfa is an effective, generally well-tolerated alternative enzyme replacement therapy. In vitro data suggest velaglucerase alfa may be internalized into cells more efficiently and have a lower rate of seroconversion. However, these results do not necessarily correlate with clinical efficacy.