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Biotech / Medical : Trimeris (TRMS) -- Ignore unavailable to you. Want to Upgrade?

To: Pluvia who wrote (85)	9/12/2000 2:36:56 PM
From: Pluvia	Read Replies (1) \| Respond to of 108

Clarification of The Anti-HIV cocktail Issue 1. Use of an anti-HIV cocktail is not new. The issue raised by the J Durant study concerns the treatment of patients who have FAILED other anti-HIV, (cocktail), drug therapies due to mutation of the patient's HIV that caused it to become drug resistant. findarticles.com 2. Durant's study showed that HIV patients who had failed previous HIV drug therapy were very successfully treated when they used a NEW cocktail of drugs selected via Genotype Testing. 3. The key was using Genotype Testing to identify the mutation in the patients HIV, so the treating physician could prescribe a new cocktail that would be more effective against the patient's specific HIV mutation/variation. 4. Prior to Durant's study, the effect of selecting new drugs for patients using Genotype Testing had NEVER been examined. What Durant discovered was patients had SIGNIFICANT HIV viral load reductions when Genotype Testing was used to identify a new cocktail of anti-HIV drugs to treat patients who had become drug resistant. 5. The problem we see with the Trimeris T-20 study is the use of two variables in their study, (T-20 and the new Genotype selected cocktail). Trimeris failed to attribute any positive effect to the Genotype selected cocktail used in their study. With two variables it is impossible to identify the role/effect of either variable, thus the T-20 study design was flawed. 6. Up to now Wall Street has attributed the anti-HIV success reported in the Phase II T-20 study to T-20. This conclusion is clearly wrong considering results of the Durant study. 7. Patients in both studies had failed previous anti-HIV treatment due to drug resistance. So both Durant and the T-20 study used the same type of patient. 8. Both Durant and the T-20 study used Genotype testing to select a NEW cocktail of anti-HIV drugs to treat their patients. This is where we see the trial design failed. 9. According to Durant's study - just using a new "Genotype Selected" cocktail of anti-HIV drugs produced EXCELLENT results. 32% of the patients in Durant's study turned HIV undetectable in 6 months. 10. The T-20 study also used a new "Genotype Selected" cocktail of anti-HIV drugs AND T-20. Thus the T-20 study introduced two variables in their study that could have been responsible for producing positive results. 11. If we compare the % of patients in the Durant study that went HIV undetectable to those in the T-20 study that went undetectable, you notice the results were almost the same - 32% in the Durant study compared to 33% in the T-20 study. trimeris.com 12. Since the Durant study demonstrated the use of a new "Genotype Selected" cocktail of anti-HIV drugs turned 32% of the patients HIV undetectable, it is only logical that the use of the same cocktail in the T-20 study produced similar effects to those patients. 13. Taking logic one step further, if we remove the effect of the "Genotype Selected" cocktail of anti-HIV drugs from the T-20 study, we might get a better understanding of T-20's role in the Phase II T-20 study. Obviously that's not possible. But if results in two similar studies are similar, with the primary difference in the studies being one used T-20, the other did not, it seems fair to say the role of T-20 must be questioned. All comments are the EXPRESS opinion of the Author(s) - All rights reserved.

To: Pluvia who wrote (85)	10/1/2000 2:26:58 PM
From: Cacaito	Read Replies (2) \| Respond to of 108

Pluvia, interesting comments, but I read the links and I do not find reference to the use of the "genotype based drug selection" as been SPECIFICALLY used during Trimeris PII study. Of course that drug changes will happen in this type of study cause it is not ethical not to do so, a larger study will be needed to account for the difference (or the lack of it)kind of the problem that Amylin went through. Please, provide if you find the specific reference of the genotyping used in Trimeris T20 pII study it will be helpful to evaluate this problem. Trimeris does used genotyping to design the T20 target, specifically some of the non-mutant areas of the viral gp41 that they aim to block. This is not the same as the Durant study. gp120 is more mutant prone than gp41, and gp41 is the one that actually binds to the cell it will attack. The cocktail drugs act via reverse transcriptase inhibition or protease inhibition, NOT at the fusion level. Even if one will select drugs by genotype it will be at different molecular level. In favor of your view is that the effect on a trial like T20 pII could be "confounded", selection will improve the patient base on the selected coktail (If it was done with that purpose, and no evidence of that I have seen in the links provided) and not due to T20. In favor of your view is that it could happen even inadvertenly just by changing the patients drugs. Trimeris pII design (and the upcoming pIII)must have this into account during analysis (actually predetermined before study start). If they did not then attributing the results to T20 is a tentative "good trend" at best, at worst just plain lack of efficacy. I have no position at the time. Price is too high even with the if one leave "confounding" issues aside.