Monday, December 27, 2010

Duplicate Abstract: NS5A inhibitors New breakthrough

The Case Of The Duplicate Abstract
Recently published @ Journal Of Hepatology on Dec 16 was a "Re-Published" abstract Entitled:

Frequently an abstract is published a few times online at different intervals, either it was presented at a liver meeting, or excepted and published in a peer review journal and then is concurrently published across the Internet (months later). Or the abstract is simply published for the purpose of purchasing the full study. However, for myself, and possibly for the newly diagnosed it sure can be confusing. ,

We may assume these duplicate abstracts are current and bringing us updated information. If a few months have elapsed we may not remember the original abstract, however once we do a search the duplicate abstract will present itself and the case of the Re-Published abstract is solved. We again are on track and even a bit disappointed that the information is not new, but only rehashed. .

The orginal abstract and addtional data on Bristol-Myers Squibb's promising drug BMS-790052. .,.

Lets start with the abstract mentioned above which was first published online in April @ the Nature Journal Of Science, Entitled "Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect".

The data published was from a Phase I clinical trial with results showing that the drug BMS-790052 achieved a 3.3-log viral load reduction that was sustained over 120 hours in two patients.

The Abstract:

Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect
The development of direct-acting antiviral agents to treat HCV has focused predominantly on inhibitors of the viral enzymes NS3 protease and the RNA-dependent RNA polymerase NS5B. .

Here we describe the profile of BMS-790052, a small molecule inhibitor of the HCV NS5A protein that exhibits picomolar half-maximum effective concentrations (EC50) towards replicons expressing a broad range of HCV genotypes and the JFH-1 genotype 2a infectious virus in cell culture.
In a phase I clinical trial in patients chronically infected with HCV, administration of a single 100-mg dose of BMS-790052 was associated with a 3.3 log10 reduction in mean viral load measured 24 h post-dose that was sustained for an additional 120 h in two patients infected with genotype 1b virus.
Genotypic analysis of samples taken at baseline, 24 and 144 h post-dose revealed that the major HCV variants observed had substitutions at amino-acid positions identified using the in vitro replicon system.
These results provide the first clinical validation of an inhibitor of HCV NS5A, a protein with no known enzymatic function, as an approach to the suppression of virus replication that offers potential as part of a therapeutic regimen based on combinations of HCV inhibitors.

EASL April 2010

In the Phase II clinical trial presented at EASL the combination of BMS-790052 with peginterferon alpha-2a and ribavirin significantly achieved a higher antiviral response than the standard therapy alone.
The virus-encoded NS5A is a multifunctional protein essential for HCV replication. NS5A represents a relatively new target and inhibitors are expected to have a broad genotypic coverage. .

Currently, Bristol-Myers Squibb's candidate BMS-790052 is the most advanced in terms of development. Results from a placebo-controlled Phase II study assessing the safety and efficacy of three different doses of BMS-790052 (3mg, 10mg and 60mg) in combination with current standard of care were presented at a late-breaker session at the EASL meeting. .

Impressive efficacy rates were observed, with 83% of patients in the BMS-790052 10mg arm achieving an extended rapid virologic response compared to only 8% in the placebo arm. The rate of adverse events was comparable across BMS-790052 dosing arms and placebo. .

Although larger studies investigating the efficacy of BMS-790052 over a longer time frame are required to confirm these results, Datamonitor believes that, on the basis of the presented data, BMS-790052 seems a promising new agent for the treatment of chronic HCV.

Presentation Date: Apr 17, 2010


Moving forward to November:

Abstract Presented At This Years AASLD Meeting:.

BMS-790052 and BMS-650032

BARACLUDE, BMS-790052, and BMS-650032 were discovered by Bristol-Myers Squibb Research and Development. PEG-Interferon lambda was discovered by ZymoGenetics, Inc. Bristol-Myers Squibb and ZymoGenetics announced a global collaboration for PEG-Interferon lambda and its related development program in 2009. In September 2010, Bristol-Myers Squibb announced its intent to acquire ZymoGenetics..

Combination therapy with BMS-790052 and BMS-650032 alone or with pegylated interferon and ribavirin (pegIFN╬▒/RBV) results in undetectable HCV RNA through 12 weeks of therapy in HCV genotype 1 null responders. ,.

The study of the two drugs BMS-790052 (NS5A inhibitor) and BMS-650032 (protease inhibitor) were given with and without pegIFN/RBV in genotype 1 null-responders.

BMS-790052/BMS-650032 Without pegIFN/RBV

At 12 weeks the two drugs BMS-790052/BMS-650032 alone acheived an early potent antiviral activity. However, 6 out of the 11 people had a viral breakthrough. ,

BMS-790052/BMS-650032 In Combination With PegIFN/RBV

The study then combined the two drugs with pegIFN/RBV and 9 out of 10 people became undetectable by week 12.

*The combination therapy was safe and well-tolerated.
The study is being expanded to include more arms, we await for the final results which are expected in 2011. ..

The Full Data :


Clinical Trials : BMS-790052.

Not yet recruiting
Study in Genotype 2/3 Subjects With Chronic Hepatitis C
Last Updated: December 8, 2010
Condition(s): Hepatitis C Virus .

An Anti-viral Combination Study With Japanese Hepatitis C Infection (HCV) Subject
Last Updated: December 2, 2010
Condition(s): Hepatitis C Infection

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