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Vertex Pharmaceuticals Incorporated Message Board

  • acslonewolf acslonewolf Feb 24, 2012 12:20 PM Flag

    Does VRTX need NS5A inhibitor?

    NVS just recently collaborated with Enanta for their NS5A. GILD and BMY has one for nuke + NS5A combos, GS7977+GS5885 / INX 189 + BMS 790052. There are some talk about INCIVEK + nuke and NS5A or with just NS5A. Does VRTX have NS5A in their studies?

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    • Lots of positive signals are in the today's Vertex CITI conference webcast. Don't forget listening to it too.

      I am sure that Vertex had been testing IDX184 for combining with Incivek before they decided to license ALS-2200 and -2158. Now that the safety issue of IDX184 has been cleared, Vertex may be looking at it again as a backup to the Alios compounds. I think that even if Alios compounds will become the next gold standard of the therapy (there is a chance for that), it will be wise to partner with IDIX and ACHN to bring out, within 3 years, a safe oral drug triple which may not be efficacious as IFN-based therapy but well tolerated by patients.

    • Vertex needs to be taken out and shot to put everyone who owns it out of their misery.

    • All HCV enzymes make up the HCV RNA replication complex which is used to reproduce the RNA. Proteases, NS5A, polymerase, others are parts of the complex. Both protease and NS5A block immune response against the RNA. However, to synthesize protease or NS5A you also need polymerase in the replication complex. So, the inhibitors have the same mechanism of action. What differentiates one inhibitor from the others is its potency and its resistance profile. If a particular NS5A inhibitor has a high barrier against viral resistance, it is desirable to have it in the mix, but it is not absolutely necessary.

      • 1 Reply to thirdmeinvestor
      • There was a conceptual quantum jump in the following quote. So replace the following,

        [However, to synthesize protease or NS5A you also needs polymerase in the replication complex. So, the inhibitors have the same mechanism of action.]

        by

        { However, to synthesize protease or NS5A, Hep C virus (HCV) also needs polymerase in the replication complex. This means that by knocking out the polymerase with VX-222, for example, you can knockout HCV's proteases NS3/4A and NS5A as well. This means that the inhibitors to the above HCV enzymes have largely the same mechanism of action.}

    • From Vertex site:


      ALS-2200 and ALS-2158 are nucleotide analogues that appear to have a high barrier to drug resistance based on non-clinical and in vitro studies. Both compounds are designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. Each compound is structurally distinct (adenosine and uracil) and has its own unique mechanism of action, which supports the potential for developing these compounds together as a dual nucleotide regimen and as part of combination therapy regimens, including regimens with INCIVEK and VX-222. Data from in vitro studies showed that both ALS-2200 and ALS-2158 had a synergistic effect when combined together and with INCIVEK and VX-222. Additionally, in vitro studies of both compounds showed antiviral activity across all genotypes, or forms, of the hepatitis C virus, including genotypes more prevalent outside of the United States.

 
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