Replies to post #132117 on Biotech Values

[genisi]

Another worry would be fibrotic patients that may lack these enzymes in their damaged livers to activate the prodrug.

[mcbio]

Pharmasset looked at the drug-drug interactions with Telaprevir in vitro and concluded that antagonistic interaction is unlikely in clinical studies given the duplicity of enzymatic pathways available for delivery of the triphosphate intracellularly.

I would tend to think VRUS has likely done DDI studies with the drugs they have signed trial collaboration agreements with (TMC435 and the BMY NS5A). Given all the value built into the VRUS nukes up to that point, you wouldn't think they would agree to do combo trials with another HCV candidate that they hadn't thoroughly vetted given the risk of potential SAEs in the combo trial. It would be difficult to determine which drug would be at fault should any SAEs arise from the clinical testing of the combo so one would think VRUS would want to have a lot of confidence in any drug they are combining with 7977. Of course, DDI studies don't always translate over to the clinic.

[jellybean]

Thanks for the reference. Actually what they said was this The in vitro antagonistic drug- drug interactions with telaprevir, an HCV protease inhibitor telaprevir currently in phase 3 studies, are unlikely in clinical studies given the duplicity of enzymatic pathways available for delivery of the triphosphate intracellularly

So there are in vitro antagonistic drug-drug interactions. Interesting. They conclude is that these interactions won't be a problem in vivo because of the duplicity of enzymatic pathways....but they did not show that.

The other thing no one mentions is that for ever molecule of 7977 metabolized a phenol is released into the cell. Not necessarily a problem, but one never knows when a drug is dosed for months at high levels.