HM10660A, a long-acting hIFN-alpha-2b, is a potent candidate for the treatment of hepatitis C through an enhanced biological half-life
- Authors
- Bae, Sungmin; Sim, Taehoon; Lim, Chaemin; Kim, Daejin; Lee, Jongsoo; Park, Youngjin; Jung, Sungyoub; Choi, Inyoung; Kwon, Sechang; Oh, Kyung Taek
- Issue Date
- Dec-2017
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- Interferon-alpha (IFN-alpha); Hepatitis C virus (HCV); IFN-alpha-2b; Cytokine; Human IgG4; HM10660A
- Citation
- INTERNATIONAL JOURNAL OF PHARMACEUTICS, v.534, no.1-2, pp 89 - 96
- Pages
- 8
- Journal Title
- INTERNATIONAL JOURNAL OF PHARMACEUTICS
- Volume
- 534
- Number
- 1-2
- Start Page
- 89
- End Page
- 96
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/3484
- DOI
- 10.1016/j.ijpharm.2017.09.074
- ISSN
- 0378-5173
1873-3476
- Abstract
- Interferon-alpha (IFN-alpha) has been widely used for the treatment of infections due to the hepatitis C virus (HCV). Because of the short half-life of IFN-alpha in serum, it must be administered three times per week. To increase the half-life of IFN-alpha, the immunoglobulin G4 (IgG4) Fc fragment (HMC001) was conjugated with human IFN-alpha-2b to develop a long-acting IFN-alpha-2b, HM10660A. An analysis of the antiviral efficacy of HM10660A in a human hepatocyte-engrafted mouse model found that HM10660A reduced serum HCV titers more effectively than a commercially available peginterferon alpha-2a (PEGASYS (R)) and IFN-alpha-2b. Pharmacokinetic (PK) and pharmacodynamic (PD) studies of HM10660A using monkeys demonstrated that the half-life of HM10660A was approximately 2-fold longer than commercially available peginterferon alpha-2a, which is approved for a once-weekly regimen. Moreover, the IFN-mediated induction profiles of neopterin and 2', 5'-oligoadenylate synthase (OAS) in normal cynomolgus monkeys indicated that HM10660A had enhanced antiviral activity and a prolonged duration of action compared with peginterferon alpha-2a. Considering the improved PK and PD properties, HM10660A can most likely be dosed every two or four weeks, providing superior antiviral efficacy and convenience for patients with HCV.
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