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Vertex Pharmaceuticals Incorporated Message Board

  • johnf50@rocketmail.com johnf50 Jul 31, 2012 9:29 AM Flag

    ALS-2200 (Vertex) Comparison to GS-7997 (Gilead)

    Taken from Thirdmeinvestor's posting - I felt it warranted it's own thread:

    I happen to have an old set of data presented by Pharmasset in a 2010 meeting.

    3-day 400mg-a-day PSI-7977 monotherapy lowers viral load by 1.95 log IU/ml,

    while

    3-day 100mg-a-day ALS-2200 monotherapy lowers viral load by 2.60 log IU/ml

    3-day 200mg-a-day ALS-2200 monotherapy lowers viral load by 3.85 log IU/ml.

    So, ALS-2200 is more powerful than 7977.

    7-day 200mg-a-day ALS-2200 monotherapy lowers viral load by 4.54 log IU/ml. This is comparable to the power of 7-day monotherapy of PSI-938, which was found to be toxic to the liver.

    If ALS-2158 is as powerful as 2200 AND well tolerated for 31 days of its safety study, this duo has the potential to rule the Hep C universe for a long time.

    Both Incivek and VX-222 lower the viral load by 3.7 log following a 3-day dosing (individually).

    ~ Thanks Third.

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    • A slide in trial results reported by Pharmasset last year gives a quite different number for the viral load reduction after 3 days of 7977 dosing. This is what I found;

      At the end of 3 days of dosing 400mg QD the viral RNA was reduced by about 3.7 log when read off from a zigzaging graph line. This is quite different from 1.95 log reduction reported in 2010. This is a 1.8 log difference. This discrepancy can be explained by the large variation in drug response from one individual to another. For Alios 2200 when dosed 100mg QD for 3 days, the viral reduction minimum was 1.81 log, the maximum was 3.78 log, and the median was 2.6 log. The difference btw the min. and max. was almost 2 log. Likewise, for the 200mg dosing, the difference btw the min and max was 1.3 log.

      Considering the role played by individual immunity against the virus and probably large variation in individuals' immunity, one can understand the above difference in drug response.

      The median viral reduction after the 7-day dosing turned out to be almost equal for 7977 and ALS-2200.

      What will differentiate the two drugs are obviously safety and tolerability.

      • 1 Reply to thirdmeinvestor
      • what will also distinguish the two is compatability using each agent incombination with other drugs for the shortest effective course resulting in sustainable SVR. Given that different 'hard to treat subpopulations of hep C will likely need a drug coctail of 3 or more oral agents for optimal results the compatabillity of agents will be important as well as each drug's safety profile used alone. (e.g. Boceprevir inhibits the efficacy of HIV meds in the co-infected patients).

    • John, hope you are doing OK withstanding the market volatility.

      As you know, just as important as the efficacy is the tolerability and resistance barrier.

      In the Q&A session of the earnings conf. call, CSO stated the following: “from a preclinical point of view, [ALS-2200 is] one of the safest, if not the safest, nukes that we have sort of seen in the landscape out there ..." They are confident about the safety of treating human for 12 weeks.

      There is a reason for the safety. Alios nucs are prodrugs which are not toxic as given in the intact form, but they are activated first in the liver where HCV is confined and killed by the activated drugs.

      The barrier to viral resistance is also very high. Alios could not find any mutated protein of NS5B polymerase after treating them with the nucs for 6 months in vitro.

      ALS-2200 is an exciting compound.

      • 1 Reply to thirdmeinvestor
      • johnf50@rocketmail.com johnf50 Aug 2, 2012 9:02 AM Flag

        Doing very well, thank you third. And thank you for the info.

        My recent absence on the boards should not indicate a lack of belief in the value of VRTX. I continue to maintain a significant holding in VRTX - but I have been far less active on the message boards and investing in financial instruments as I have about 25 mil under construction now - which translates into roughly 80 + hours a week and I am still always behind.

        As far as market volatility - I am a graham dodd student and rolled a good chunk of my money into inflation protected bonds - The rest of my equities were highly valued so I began to sell calls. The only position I have had called was GE, - but I made roughly 15% by both appreciation and lowering my cost basis with the derivatives. With the recent boom on VRTX and the call positions I had - I am still over 300% for the year.

        I was 500% but made a highly wagered 'bet' that the alios nuc data would have come out in 2Q:12 as indicated in the prior conference call - those options expired worthless a couple of weeks ago.

        My next wager on VRTX would be that as forecasted - the 31 day Alios data will be out in October - and AASLD is in November... still deciding how much to put on that horse - but will probably initiate marginally risky call position in the next week or so and see what happens.

    • What Vertex needs to do now is to figure out the right clinical trials and execute ASAP. Vertex has been slow in clinical development in the past, and now can not afford to be slow on this again.

      • 1 Reply to applejungle
      • Yes, I agree, Vertex has the tendency to design very complex or conservative trials so they cover the basis to minimize the risk of capital loss or to cover more ground so the data guides better trials in the future.

        The benefit of designing conservative trials is that the path for approval is more secure and/or risks less capital. Complex trials are slow but cover many bases and guides future clinical design for better chances of approval. At the same time small trials are slow (e.g. splitting phase II in Phase IIa and phase IIb) but they risk less capital if the trial fails.

        On the contrary, a more aggressive trial with fewer arms has the benefit to accelerate approval if the data is positive, but if it is not it may lose the chance to be informative, so that there is a larger risk of failing and having to re-do the trials ... very expensive and at the end may be slower.

        The question is to make the right choices for clinical design ... never easy, and even more difficult in Hep C with so many combo opportunities ...

 
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