"If NVS and IDIX can produce data showing that Tyzeka and Viread are additive before BMY can produce data showing that Baraclude and Viread are additive, it will be yet another differentiating factor in favor of Tyzeka in its competition with Baraclude"
BMY and IDIX/NVS are literally neck and neck in tenofovir combination studies, having begun recruitment within a couple months of one another
IDIX/NVS is ahead of BMY in combination studies of their respective agents combined with adefovir
I think it is important to distinguish between potency and resistance, although the two are not mutually exclusive. at the end of the day the ultimate goal is to achieve prolonged viral suppression (forget the SVR/cures touted by vrus for the time being)
adefovir has low potency (due to dose-limiting toxicity issues), but a high barrier to resistance, so decent sustained viral suppression can be achieved, but eventuallym, with very long exposure, high resitance rates are seen (probably related to the relatively low potency allowing virions to eventually develop resistance over time). tenofovir is basically identical to adefovir, but without the dose-limiting toxicity (renal i believe), so you can ramp up the dose and get both high potency and a high barrier to resistance. so imo tenofovir (cost issues notwithstanding) will ultimately supplant adefovir totally.
so where does this leave entecavir and telbivudine? well entecavir has high potency and high barrier to resistance, so it might be able to battle tenofovir head to head as first line. BUT, if combination therapy gains traction (and it sure looks like all 3 companies think it will based on the series of phase 3/4s out there), then it really will boil down to which nucleoside/nucleotide combo gives the best bang for the buck..and when talking combos:
1. costs will start to hold greater sway in decision-making/preferred insurance carrier coverage, because now you're suddenly talking >10-12K annually per pt in medication costs
2. the synergy of 2 agents may result in such a high viral suppression/low resistance rate that any advantage one agent has over the other as monotherapy very well may vanish, in which case the low-cost/least toxic/more convenient dosing regimen will likely prevail in the marketplace (or at that point even an even split would be a huge boon for idix/nvs)
3. we haven't heard a word about the entecavir/telbivudine head to head viral suppression study yet, but an extension study of that initial 12 week trial is ongoing. we'll soon have mroe clarity on how these agents stack up to one another as monotherapy, and I am sure there will be provisions for those patients breaking through so we may see what kind of cross-resistance is generated..here again a tie favors telbivudine, seeing as how the prevailing sentiment (despite NO head to head data to date) strongly favors entecavir
AI
