Zimran A
Shaare Zedek Medical Center, Jerusalem, Israel.
Drugs Today (Barc). 2011 Jul;47(7):515-29. doi: 10.1358/dot.2011.47.7.1608922.
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.
1型戈谢病（GD）由遗传性β-葡萄糖脑苷脂酶基因突变引起，可导致贫血、血小板减少、脾肿大、肝肿大和骨骼疾病。维拉苷酶α是一种通过人类细胞系基因激活产生的β-葡萄糖脑苷脂酶，用于治疗1型GD。一项I/II期临床试验（TKT025；N = 12）、其正在进行的扩展试验（TKT025EXT）以及三项III期试验（总计N = 82）表明，维拉苷酶α在成人和儿科患者中总体耐受性良好。在两项针对初治患者的III期试验中，许多与疾病相关的参数有显著改善，并且在一项II/III期转换研究中，在接受过伊米苷酶治疗的患者中这些改善得以成功维持。TKT025EXT中的10名成人患者在5年中持续改善，包括骨密度。与伊米苷酶相比，维拉苷酶α是一种有效的、总体耐受性良好的替代酶替代疗法。体外数据表明，维拉苷酶α可能更有效地被细胞内化，并且血清转化率较低。然而，这些结果不一定与临床疗效相关。
