Preclinical and clinical development of pegylated interferon-lambda 1 in chronic hepatitis C.

Abstract

Current treatment of chronic hepatitis C consists of pegylated interferon-alpha (PEG-IFN-alpha) in combination with ribavirin. This regimen is associated with adverse effects that can limit its use. PEG-IFN-lambda 1 (pegIFNlambda) is a novel IFN that shares many of the biological effects of IFN-alpha but may have fewer side effects due to its more selective receptor distribution. Preclinical data show that pegIFNlambda has antiviral activity against hepatitis C virus (HCV) but does not inhibit myeloid colony formation. A phase 1 study in healthy volunteers demonstrated that pegIFNlambda is well tolerated. Elevated liver enzymes resulted in a dose-limiting toxicity after a single dose of 7.5 microg/kg, the highest dose tested. A phase 1b study in genotype 1 HCV patients who either relapsed after IFN-alpha therapy or naive to therapy was initiated. Interim data from the treatment relapse subset showed viral load reductions of 2.3 to 4.0 logs when pegIFNlambda was administered weekly as a single agent with or without ribavirin for up to 4 weeks. Drug-related side effects included elevation of liver enzymes. Decreases in hemoglobin were observed only in patients receiving ribavirin. Constitutional symptoms appeared lower than historical data for PEG-IFN-alpha. These results form the basis of further development of pegIFNlambda as a novel treatment for chronic hepatitis C.

• Authors: Eleanor L Ramos
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 30 Issue 8 Pg. 591-5 (Aug 2010) ISSN: 1557-7465 [Electronic] United States
• PMID: 20645873 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antiviral Agents
• IFNL1 protein, human
• Interferon alpha-2
• Interferon-alpha
• Interleukins
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• Interferons
• peginterferon alfa-2a

Topics

• Adult
• Aged
• Antiviral Agents (administration & dosage, adverse effects)
• Bone Marrow (drug effects, metabolism, pathology)
• Clinical Trials, Phase I as Topic
• Drug Evaluation, Preclinical
• Drug Therapy, Combination
• Female
• Hepacivirus (pathogenicity, physiology)
• Hepatitis C, Chronic (drug therapy, immunology)
• Humans
• Interferon alpha-2
• Interferon-alpha (administration & dosage, adverse effects)
• Interferons
• Interleukins (administration & dosage, adverse effects, chemistry)
• Male
• Middle Aged
• Polyethylene Glycols (administration & dosage, adverse effects, chemistry)
• Recombinant Proteins
• Ribavirin (administration & dosage, adverse effects)
• Viral Load (drug effects)