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Fw: NATAP: New Hep C Drugs Review

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  • AlleyPat
    This email contains pictures. If the pictures don t come thru on the list, go to the natap site and research the article..... Alley NATAP http://natap.org/
    Message 1 of 3 , Dec 5, 2006
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      This email contains pictures. If the pictures don't come thru on the list, go to the natap site and research the article..... Alley


      NATAP http://natap.org/
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      New Hepatitis C Drugs

      Presented by Markus Cornberg, Germany, at the 2nd European Viral Hepatitis Educational Initiative, Nov 23-24, 2006, Frankfurt, Germany.


      SMALL MOLECULES- Viral replication Cycle & Identiying Potential Targets



      TARGETS

      Virus Entry
      CD81 Receptor (no drugs available yet)


      Inhibition of Protein Synthesis (Ribozymes)


      MOST PROMISING TARGETS SO FAR NS3 PROTEASE INHIBITORS & POLYMERASE INHIBITORS


      PROTEASE INHIBITORS


      VX-950 Very Potent, 4.4 log decline in naives, 99.9% reduction in viral load after 14 days. But has to be dosed every 8 hours and resistance can develop, re-emergence of pre-existing mutations.


      WE MAY FACE CROSS-RESISTANCE ISSUES. BUT PEGINTERFERON SUPPRESSED PI RESISTANT MUTANTS



      COMBINATION OF VX-950 & PEGINTERFERON SUPPRESSED RESISTANCE MUTATION & REDUCED VIRAL LOAD BY 5.5 log after 14 days. Triple therapy: 12/12 patients undetectable (<10 IU/ml) after 28 days therapy with VX950/pegINF/RBV, â?o5/6 SVRâ?. â?oWe may achieve 80% SVR rate after 12-24 weeksâ?.



      Gilead/Achillon drug ACH-806 Interacts with NS3 Protease but in a different way, drug. Showed strong in vitro potency. Showed resistance mutations but not cross-resistant in vitro was sensitive to other protease inhibitors.


      HCV POLYMERASE INHIBITORSâ?¦many in development


      NM283 polymerase inhibitor. 1 log reduction in viral load



      ROCHE R1626 POLYMERASE INHIBITOR showed -3.7 log reduction in viral load after 14 days in naives but associated with side effects at higher dose so lower dose may be developed.


      MERCK POLYMERASE INHIBITOR SHOWED 5.7 log reduction in viral load after a few days of treatment in chimpanzees.


      CYCLOPHILIN B INHIBITION inhibits polymerase.


      In vitro active against HCV but can be immunosuppressive.


      DEBIO-25 reduced viral load by 3.6 log after 15 days therapy.


      Glucosidase inhibitors inhibit assembly of virus.


      WE MAY NOT BE ABLE TO ACHIEVE SVR WITHOUT IMMUNOMODULATION, â?oit's a â?omillion dollar questionâ?. Toll-like receptors & therapeutic vaccines may work.



      COMBINATION THERAPY: FUTIRE OF HCV THERAPY. â?oPerhaps ritonavir boosted protease inhibitors will reduce 3 times a day dosingâ?. â?oWe may be able to achieve 80-100% SVR in the futureâ?.





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    • Rep
      Hey gang, Does anyone know where to go look for clinical trials? there used to be a lot of Hep C drug trials going on. What s the deal? I can t find hardly
      Message 2 of 3 , Feb 9, 2007
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        Hey gang,
        Does anyone know where to go look for clinical trials? there used to
        be a lot of Hep C drug trials going on.
        What's the deal? I can't find hardly anything.

        Bob
      • alleypat
        clinicaltrials.gov/ is where I look Alley [Non-text portions of this message have been removed]
        Message 3 of 3 , Feb 9, 2007
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          clinicaltrials.gov/ is where I look

          Alley

          [Non-text portions of this message have been removed]
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