Replies to post #117698 on Biotech Values

[dewophile]

the next gen are definitely more potent, but i was referring specifically to rate of conversion of RVR to SVR, so the group who seemingly had adequate potency on RG7128
now ti could be that knocking down virus even faster than 4 weeks - say undetectable at 1-2 weeks - will equate to SVR at a higher rate than undetectable at 4 weeks so your point is well taken
certainly there will be more RVRs on the newer nukes, but lets say the conversion to SVR is similar and you get 1005 RVR with combo - so 76% of pts with RVR get to SVR so efficacy is 76%. what regimen would you go on - one that added SOC for say 24 weeks that had a 90% SVR or an all oral that had 75%? of course it's more complicated than that since VRUs is cleverly testing shortened durations of interferon so it may be 76% without soc and another 10%+ with 4-12 weeks of interferon and rib. and how does that change if the interferon is lambda which is more tolerable?
jsut random thoughts as i think this through..

[DewDiligence]

I think VRUS's first generation nuke RG7128 unlike the latest-generation HCV nukes is also not potent enough.

I doubt that any HCV nucleoside (as opposed to a monophosphate nucletide) could be potent enough to be a bona fide contributor in an all-oral cocktail. Performing the first phosphorylation step in vivo is too inefficient and too variable from patient to patient to allow the active triphosphate metabolite to reach a therapeutic concentration in all patients without causing unacceptable toxicity from the parent drug.

In other words, I don’t think RG7128 per se lacks potency, but rather that all first-generation nukes lack potency because they are nucleosides. That’s why I opined in #msg-61760351 that the first-generation HCV nukes and the second-generation HCV nukes are effectively two different classes of drugs.