April 23, 2012
Download PDF
Press Highlights Section Editor:
Grace L. Su, MD, University of Michigan Medical School
Story By:Kristine Novak, PhD, Science Editor, AGA Journals
New approaches to treating patients with hepatitis C virus (HCV) infection, and predicting how they will respond to therapy, were presented at the International Liver Congress (ICL) in Barcelona Spain last week.
The standard approach to assessing the efficacy of therapies for HCV infection involves determining if patients have a sustained viral response (SVR; an undetectable level of virus)at 24 weeks after therapy. It therefore takes about 6 months after therapy is completed to determine if a potential drug works.
Eric Lawitz et al. reported last Thursday that we might not need to wait that long. In studies of the antiviral agent GS-7977 (previously known as PSI-7977), all patients who had an SVR at 4 weeks after therapy ended maintained the response 24 weeks after therapy. This means that
clinicians might be able to tell within a month after completion of therapy whether it was successful.
Lawitz et al. analyzed data from 3 large clinical trials (the PROTON, ATOMIC, and ELECTRON trials) of the uridine nucleotide analog GS-7977. The drug was being tested in interferon-containing and in interferon-free regimens for treatment-naïve patients with HCV genotype 1, 2, or 3 infections. They found that 100% of the patients with a SVR at week 4 maintained the SVR at week 24, and that none of these patients has had a relapse of the infection.
Lawitz et al. conclude that the absence of on-treatment viral breakthrough and lack of relapse among patients that have an SVR by week 4 indicate that GS-7977 suppresses HCV to a level that is beyond the range of current assays, and confirms that the virus is will not easily acquire mutations that make it resistant to the drug.
“We have to be careful in translating concordance versus cure” warned Lawitz after his presentation, but he proposes that SVR4 is a good biomarker of efficacy for these types of reagents.
Audience members pointed out that all the studies were performed in patients with low stages of fibrosis, and Lawitz agreed that further studies are needed to determine whether these findings will hold for patients with more advanced-stage hepatitis.
Mark Thursz, Secretary General of the European Association for the Study of the Liver (EASL),which sponsored the ICL, asked “Is SVR4 the new SVR24?” He says that it is something we have to take seriously.
In a separate talk, Stefan Zeuzem reported that interferon-λ is just as effective and producesfewer side effects than interferon-α in non-cirrhotic patients infected with HCV genotypes 2 or 3. Most patients with chronic HCV infection receive interferon-α therapy, which frequently produces significant adverse events.
In the first results reported from the EMERGE Phase 2b trial, Zeuzem showed that interferon-λ led to a more rapid decay of HCV RNA in 526 treatment-naïve patients. Of patients that received weekly doses of 180 μg of interferon-λ, 80% had an SVR at week 24, compared with 53% that received the same dose of interferon-α. Genotypes of IL-28B did not appear to affect the response to interferon-λ.
Furthermore, significantly fewer patients given interferon-λ experienced the flu-like symptoms,fatigue, myalgia, athraligia, and musculoskeletal symptoms that developed in the patients given interferon-α. Fewer also discontinued therapy or had to reduce their dose, and adverse events
were rare.
Interferon-λ is a type III interferon that is active against all genotypes of HCV—particularly against genotype 3, which is hard to eradicate. The limited tissue distribution of its receptor might account for the fewer side effects it produces, compared with interferon-α.
Abstracts:
E Lawtiz et al. Abstract 7, EASL International Liver Congress 2012
S Zeuzem et al. Abstract 10, EASL International Liver Congress 2012
RETURN TO GASTROENTEROLOGY
were rare.
Interferon-λ is a type III interferon that is active against all genotypes of HCV—particularly against genotype 3, which is hard to eradicate. The limited tissue distribution of its receptor might account for the fewer side effects it produces, compared with interferon-α.
Abstracts:
E Lawtiz et al. Abstract 7, EASL International Liver Congress 2012
S Zeuzem et al. Abstract 10, EASL International Liver Congress 2012
RETURN TO GASTROENTEROLOGY
No comments:
Post a Comment