HM10660A, a long-acting hIFN-α-2b, is a potent candidate for the treatment of hepatitis C through an enhanced biological half-life

摘要

Graphical abstract Display Omitted Abstract Interferon-α (IFN-α) has been widely used for the treatment of infections due to the hepatitis C virus (HCV). Because of the short half-life of IFN-α in serum, it must be administered three times per week. To increase the half-life of IFN-α, the immunoglobulin G4 (IgG4) Fc fragment (HMC001) was conjugated with human IFN-α-2b to develop a long-acting IFN-α-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 α-2a (PEGASYS ? ) and IFN-α-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 α-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 α-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.