Its the end of the week already, where does the time go? On the blog today is a small rewind of this weeks news, research and updates. Click here to view previous or future"HCV Weekly Rewind" articles.
This week coverage on the EASL continues at HIV and Hepatitis C, NATAP, Medscape and this blog with interim results on new and experimental hepatitis C drugs.
An interesting development which has been slowly emerging is the possible new standard for reporting SVR results on new HCV drug regimens in clinical trials.
SVR12 by researchers is now being compared to SVR24. As it stands SVR- (sustained viral response or cure) is determined by an undetectable viral load-(level of virus) 6 months after therapy is completed. Offered in this post today are two excerpts and an article discussing SVR4 and SVR12 from the clinical data presented at the EASL, followed up by links to full results.
We begin with a few drug regimens in development presented at the meeting last month, for instance-Abbotts ABT-450/r and ABT-072.
Excerpt- SVR12 end point seen in the small pilot study.
In a pilot study of 11 treatment-naive noncirrhotic patients, 91% achieved a sustained virologic response at 12 weeks after the end of treatment (SVR12), and 82% had a sustained virologic response at 36 weeks (SVR36).
"If these very late relapsers are just 1% or 2%, then it will be of no clinical relevance.... If it's really 1 of 11 (so close to 10%), these late relapsers will be very important," he said. "Because these are new regimens, we don't know how the responders will behave in the long term, so I think the SVR12 should be the gold standard for reporting the results of the trials. [In addition], all trials should still have at least 1 HCV RNA follow-up...1 year after these SVR12 determinations."
View complete article @ Medscape-Two Oral Drugs Clear HCV Without Interferon- by Daniel M. Keller, PhD.
Next up is GS-7977 from Gilead Sciences and the ATOMIC and PROTON trials-view full data @ Medscape.
Excerpt; Mark Thursz, MBBS, MD comments in the article on SVR4 data and the FDA's interest in SVR12 as an end point........
Session moderator Mark Thursz, MBBS, MD, professor of hepatology in the Department of Medicine at Imperial College, London, United Kingdom, and secretary general of the European Association for the Study of the Liver, who was not involved in the ATOMIC trial, said during a news conference that SVR24, an absence of viremia for 6 months after the end of treatment, has been the standard definition of cure until recently. Now, "we've started to become used to SVR12 as an end point. I understand that the FDA [US Food and Drug Administration] is now interested in SVR12 if it can be subsequently established as meaning a cure," he said.
"Now the companies are coming to us with SVR4 data.... SVR4 certainly predicts the final outcome. It may not be quite the same as the cure rate, the SVR24 rate, but it's pretty close and gives us a very good indication," Dr. Thursz explained. The implication is that when abstracts are submitted to meetings, "SVR4 is something that we have to take seriously...whereas previously we would regard [the results] as merely interim data," he said.
In the below article we have yet another reason to take SVR4 durability seriously, according to three GS-7977 clinical trials; PROTON, ATOMIC, and ELECTRON- "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."
More Ways to Treat HCV Infection and Measure Response
April 23, 2012
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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.
Now For A Few Articles Of Interest This Week
More on HIV and Poverty in the U.S.
By Jessica Wapner
Posted: May 4, 2012
Many years ago, some friends of mine in Israel dug a hole. I don’t remember now what they were searching for, but they thought there was something a ways down, so they dug. It took a while, and in the…
FDA Must be Proactive About Postapproval Drug Safety: IOM
04 May 2012
Obese people who consume increased amounts of fructose, a type of sugar that is found in particular in soft drinks and fruit juices, are at risk for nonalcoholic fatty liver disease (NFALD) andmore its more severe forms...
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For Your Reading Pleasure
May Begins With Hepatitis C Disease Management, Drugs and Research
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Off Topic
Watch the NEJM Documentary, Getting Better
This 45-minute documentary explores three remarkable stories of medical progress that have taken place over the course of the long history of NEJM. In 1812, we had no understanding of infectious disease, surgery was unsanitary and performed without anesthesia, and cancer was unrecognized. Two centuries later, this film tells the story of research, clinical practice, and patient care, and of how we have continued to get better over the last 200 years.
Enjoy your weekend !
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