Interferons induce pleiotropic biologic responses which include antiviral, antiproliferative, and immunomodulatory effects, regulation of cell surface major histocompatibility antigen (HLA class I and class II) expression and regulation of cytokine expression.
Interferon alfacon-1 is an inducer of the innate antiviral immune response. Interferon alfacon-1 is a recombinant hybrid protein based on the consensus amino acid sequence of naturally occurring human type-I interferon alphas. Type-I interferons are a family of small protein molecules with molecular weights of 15,000 to 21,000 daltons that are produced and secreted by cells in response to viral infections or to various synthetic and biological inducers. Interferons do not act directly on the virus but bind to the interferon cell-surface receptor leading to the production of several interferon-stimulated gene products. Interferons induce pleiotropic biologic responses which include antiviral, antiproliferative, and immunomodulatory effects, regulation of cell surface major histocompatibility antigen (HLA class I and class II) expression and regulation of cytokine expression.
Analysis of interferon alfacon-1-induced cellular products (induction of 2’5' OAS and β-2 microglobulin) after treatment in these subjects revealed a statistically significant, dose-related increase in the area under the curve (AUC) for the levels of 2’5' OAS or β-2 microglobulin induced over time. Concentrations of 2’5' OAS were maximal at 24 hours after dosing, while serum levels of β-2 microglobulin appeared to reach a maximum 24 to 36 hours after dosing. The dose-response relationships observed for 2’5' OAS and β-2 microglobulin were indicative of biological activity after subcutaneous injection administration of 1 mcg to 9 mcg interferon alfacon-1.
The antiviral activity of interferon alfacon-1, alone or in combination with ribavirin, against HCV or HCV-derived replicons in cell culture has not been determined.
HCV genotypes show wide variability in their response to interferon/ribavirin based therapies. Genetic changes associated with the variable response have not been identified. It has been reported that certain regions of the HCV genome, especially a region in the NS5B protein called IFNsensitive determining region, may play a role in determination of a patient’s response to interferon treatment.
The homology between interferon alfacon-1 and other type-I interferons, and the clinical responses for the different HCV genotypes are consistent with cross-resistance.
The pharmacokinetic properties of interferon alfacon-1 have not been evaluated in patients with chronic hepatitis C. Pharmacokinetic profiles were evaluated in normal, healthy volunteer subjects after subcutaneous injection of 1 mcg, 3 mcg, or 9 mcg interferon alfacon-1. Plasma levels of interferon alfacon-1 after subcutaneous injection administration of any dose were too low to be detected by either enzymelinked immunosorbent assay (ELISA) or by inhibition of viral cytopathic effect.
Patients with creatinine clearance <50 mL/min should not be treated with ribavirin.
In preclinical toxicology studies in golden Syrian hamsters and rhesus monkeys, administration of interferon alfacon-1 at doses of up to 100 mcg/kg/day was associated with decreased body weight, decreased food consumption, and bone marrow suppression. High-dose chronic exposure at doses of 10 mcg/kg/day to 100 mcg/kg/day (50-fold to 500-fold higher than the maximum clinical dose given daily) in rhesus monkeys was not tolerated for greater than 1 month, due to the development of vascular leak syndrome.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
