Subramanian G Mani, Fiscella Michele, Lamousé-Smith Araba, Zeuzem Stefan, McHutchison John G
Human Genome Sciences, Inc., 14200 Shady Grove Road, Rockville, Maryland 21042, USA.
Nat Biotechnol. 2007 Dec;25(12):1411-9. doi: 10.1038/nbt1364.
Treatment regimens based on the use of interferon-alpha (IFN-alpha) remain the cornerstone of therapy for chronic hepatitis C virus infection, which affects nearly 170 million people worldwide. Treatment options include unmodified IFN-alpha given three times weekly or pegylated IFNs given once weekly. The albumin-fusion platform takes advantage of the long half-life of human albumin to provide a new treatment approach that allows the dosing frequency of IFN-alpha to be reduced in individuals with chronic hepatitis C. Albinterferon alpha-2b (alb-IFN), a recombinant polypeptide composed of IFN-alpha2b genetically fused to human albumin, has an extended half-life and early evidence indicates that it is efficacious and well tolerated. Pharmacodynamic modeling supports treatment with alb-IFN at 2- or 4-week intervals. Phase 3 registration trials are in progress. The albumin-fusion platform is currently being applied to other important bioactive peptides with short half-lives. These fusion proteins, which are at present in different phases of clinical development, might lead to improved therapies across a broad range of diseases.
基于使用α干扰素（IFN-α）的治疗方案仍然是慢性丙型肝炎病毒感染治疗的基石，全球近1.7亿人受该疾病影响。治疗选择包括每周三次给予未修饰的IFN-α或每周一次给予聚乙二醇化IFN。白蛋白融合平台利用人白蛋白的长半衰期提供了一种新的治疗方法，可降低慢性丙型肝炎患者中IFN-α的给药频率。Albinterferon alpha-2b（alb-IFN）是一种由IFN-α2b与人类白蛋白基因融合而成的重组多肽，具有延长的半衰期，早期证据表明其有效且耐受性良好。药效学模型支持每2周或4周使用alb-IFN进行治疗。3期注册试验正在进行中。白蛋白融合平台目前正在应用于其他半衰期短的重要生物活性肽。这些目前处于临床开发不同阶段的融合蛋白可能会带来针对广泛疾病的改进疗法。
