Novo Nordisk A/S, Medical and Science, Haemophilia, Søborg, Denmark.
Haemophilia. 2011 Jul;17(4):695-702. doi: 10.1111/j.1365-2516.2010.02481.x. Epub 2011 Mar 22.
Discrepancies between the one-stage clotting assay and the chromogenic method, and also among different variations of each method, have been a significant challenge for one B-domain deleted FVIII product. N8 is a B-domain truncated FVIII product developed by Novo Nordisk. The comparison of N8 and Advate(®) was performed in an international, multicentre, randomized and blinded field study of simulated postinfusion samples. Overall, Advate(®) and N8 performed similarly in the one-stage assay. In the one-stage clotting assay, the measured mean FVIII levels of Advate(®) vs. N8 were 0.046/0.047, 0.24/0.24, 0.58/0.60 and 0.82/0.83 IU mL(-1) for the target values of 0.03, 0.2, 0.6 and 0.9 IU mL(-1) , respectively. In the chromogenic assays, the concentration estimates showed a tendency towards higher N8 values as compared with Advate(®) ; the measured FVIII levels of Advate(®) vs. N8 were 0.030/0.032, 0.22/0.24, 0.65/0.74 and 0.98/1.08 IU mL(-1) for the target values of 0.03, 0.2, 0.6 and 0.9 IU mL(-1) , respectively. In the one-stage assays, the measured values were above 150% of target at the lowest concentration, decreasing to around 90% of target at the highest concentration. In contrast, the chromogenic assays were close to target at the lowest concentration and consistently above target at the three highest concentrations. Therefore, the ratio of chromogenic/one-stage potencies was concentration dependent, ranging from 0.66 to 1.30. The SSC plasma standard was similar in both. Assay variability was similar for both compounds. The results show that N8 can be reliably measured in plasma without the need for a separate N8 standard.
在一项国际、多中心、随机和盲法的模拟输注后样本现场研究中，对比了 Novo Nordisk 开发的 B 域缺失型因子 VIII 产品 N8 与 Advate(®)。在一期凝血检测中，Advate(®)与 N8 的平均 FVIII 水平测量值分别为 0.03 IU/mL、0.24 IU/mL、0.58 IU/mL 和 0.82 IU/mL，对应的目标值分别为 0.046 IU/mL、0.24 IU/mL、0.60 IU/mL 和 0.83 IU/mL。在显色法检测中，浓度估计值显示 N8 值有偏高的趋势；Advate(®)与 N8 的平均 FVIII 水平测量值分别为 0.030 IU/mL、0.22 IU/mL、0.65 IU/mL 和 0.98 IU/mL，对应的目标值分别为 0.032 IU/mL、0.24 IU/mL、0.74 IU/mL 和 1.08 IU/mL。在一期凝血检测中，在最低浓度时测量值高于目标值的 150%，在最高浓度时降至约 90%。相比之下，在显色法检测中，在最低浓度时接近目标值，在三个最高浓度时始终高于目标值。因此，显色法/一期效价比值随浓度而变化，范围为 0.66 至 1.30。两个检测方法中的 SSC 血浆标准物相似。两种化合物的检测变异性相似。结果表明，N8 可在无需单独 N8 标准品的情况下，在血浆中可靠地测量。
