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Vertex Pharmaceuticals Incorporated Message Board

  • thirdmeinvestor thirdmeinvestor Dec 27, 2007 5:52 PM Flag

    Thought-provoking articles in Nature Btk

    If you click the link below, you should find an article which discusses Telaprevir. It is written for non-specialists by a journalist ... some ideas are not precise and contain misleading statements. Ex.: John Alam was quoted a couple of places, but it sounds like as if he does not understand the molecular mechanism underlying how protease inhibitors destroy HCV. It is more likely that because the writer took his remark out of the context

    Here are the first two paragraphs of the article.

    2007 was a good year for hepatitis C?for the virus, that is. Companies, including seven biotechs, abandoned or suspended at least eight antiviral drugs in clinical development over the course of the year. "There have been quite a few compounds that have bitten the dust lately," notes virologist Charles Rice of Rockefeller University in New York. The disappointments are nothing new: drugs specifically targeting the hepatitis C virus (HCV) have been in the works since the early 1990s, but no such compound has yet advanced to phase 3 trials.

    But 2008 and beyond promise better. A compound from Cambridge, Massachusetts?based Vertex Pharmaceuticals should begin phase 3 trials by early in the year, and both biotech and pharma continue to pour resources into new therapies (Table 1). "People have been saying for the last 15 years that there's a new specific antiviral therapy that'll be approved in 5 years," says Rice. "That's turned out to be not very realistic. But I think we're finally in a place where that's likely to happen."

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    • Here's a link to the full text of the article for anyone who prefers not to download & open a .pdf file:

      Ann D.

    • The article contains the following statements. They are not accurate.

      " ... Those implications involve how the virus is destroyed. A seemingly bedrock truth about HCV is that it's not enough to stop RNA replication (the goal of targeted therapies like telaprevir); one must also eradicate the virus from the body by harnessing the immune system to clear infected cells. (Unlike with HIV, merely suppressing HCV viral load has not been shown to improve clinical outcomes.) >>No one knows why roughly half of patients don't respond to interferon and ribavirin<<, but it's assumed they have intrinsic immune system defects that prevent them from clearing infected cells. Such defects, by definition, can't be overcome using targeted antivirals like telaprevir because >>>all they do is stop RNA replication, and thus the virus remains, ready to rebound<<< ...".

      >> <<: The reason more than half of patients cannot be cured by SOC alone is because HCV use their protease to sabotage host immune response against them. This has been shown many times by lab experiments. The reason SOC works for some patients is that some HCV does not have a perfect protease to 'plot' uncanny sabotage.

      >>> <<<: Telaprevir does more than stopping HCV protein processing. It can block the sabotage mentioned above by disabling HCV protease.

      " ... The 24-week telaprevir treatment is controversial -and potentially paradigm shifting - because it challenges conventional wisdom, which holds that the adaptive immune system needs the full year to clear infected hepatocytes. Telaprevir's superior SVR rates in phase 2 compared with interferon and ribavirin alone suggests that >the immune system plays a much smaller role than previously thought< and that just stopping RNA replication may be enough to cure patients.

      > <: Not true again. Immune system plays a huge role in killing HCV with the help of TVR.

      " ... Targeted therapies like telaprevir "are all about driving down viral replication and targeting the virus, but not touching the immune system," says Vertex executive VP and chief medical officer John Alam. Viral RNA, its replication halted, may simply degrade within liver cells, Alam speculates. If the patient's adaptive immune system is not dictating their ultimate response, "maybe, eventually, there is no limit to who we can actually cure" with targeted therapy, he says...."

      What John said is true in a strict sense of words, but does not emphasize the importance of what he later called "derepression" of the immune system by the protease inhibitor.

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