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.
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