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.
Shaare Zedek Medical Center, Jerusalem, Israel. azimran@gmail.com
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Zimran
D000818:Animals; D002986:Clinical Trials as Topic; D005776:Gaucher Disease / Q000188:drug therapy*; D005962:Glucosylceramidase / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans
D005962:Glucosylceramidase; C550184:Velaglucerase alfa, human