December 28, 2010

Pegylated Interferon-Lambda for Chronic Hepatitis C Virus Infection

Summary and Comment

In a phase Ib study, PEG-IFN-Lambda showed promise in both treatment-naive and relapsing patients.

The cornerstone for treating patients with hepatitis C virus (HCV) infection is pegylated interferon alfa (PEG-IFN-alpha ) plus ribavirin. However, adverse effects can reduce quality of life, lead to dose reductions, and even prompt discontinuation of therapy, with potential consequences for efficacy. Interferon-Lambda1, also known as interleukin-29, has shown in vitro antiviral activity similar to that of PEG-IFN-apha Unlike the widely distributed IFN-alpha  receptors, expression of the IFN-Lambda1 receptor is more restricted, suggesting that a treatment that targets IFN-Lambda1 might be less prone to cause adverse effects.

In an industry-funded, open-label phase-Ib study, investigators tested the efficacy of PEG-IFN-Lambda in HCV genotype 1–infected patients. Twenty-four patients who had relapsed on PEG-IFN-alpha therapy received PEG-IFN-Lambda monotherapy (1.5 µg/kg or 3.0 µg/kg, either weekly or twice weekly), 25 patients who had relapsed on IFN-alpha therapy received PEG-IFN-Lambda (0.50–2.25 µg/kg weekly) plus ribavirin, and 7 treatment-naive patients received PEG-IFN-Lambda (1.5 µg/kg weekly) plus ribavirin. All treatments lasted 4 weeks; antiviral and safety assessments were made for at least another 4 weeks.

In two of the seven treatment-naive patients, HCV became undetectable by week 4. All PEG-IFN-Lambda doses induced virologic response, in a roughly dose-related pattern. Flu-like symptoms were uncommon; hematologic abnormalities were observed only in relation to use of ribavirin. The most commonly reported adverse symptoms were fatigue (29%), nausea (12%), and myalgias (11%). The incidence of adverse events was not dose related.

Comment: Current and future HCV therapies are likely to use interferon as the backbone. In this study, PEG-IFN-Lambda had strong antiviral activity with minimal adverse effects. If later-phase trials confirm the virologic response and low incidence of adverse effects, PEG-IFN-Lambda could become the foundation of future treatment regimens. Both treatment-naive and relapsing patients might then have treatment options that are more effective, better tolerated, and less likely to be discontinued than currently available therapies.

David A. Johnson, MD

Published in Journal Watch Gastroenterology December 22, 2010

Muir AJ et al. Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection. Hepatology 2010 Sep; 52:822.

Medline abstract (Free)

No comments:

Post a Comment