Replies to post #74807 on Biotech Values

[ghmm]

INFORM:

I believe the synergistic effect is mainly attributed to ITMN-191 since a synergistic effect was also observed when ITMN-191 was combined with IFN+Rib (looks more like additive effect for pharmaset' drug in triple combo based on the graph you have provided). Given that the triple combo of ITMN-191 at 100q8h and 200q8h did not show a huge difference, I speculate that the ITMN-191 200q8h/R7128 500 BID conhort will likely not exceed -4.5log.

Interesting speculation and you could very well end up being right on the log reduction. I think there are a few things to consider though:
1) The triple combo study had viral load reductions in the mid 5's at 100mg q8 so it wasn't like the 200mg q8 could go up a couple more logs.
2) The triple combo used IFN and Riba and I am not sure we can say a combo with a polymerase will behave in a like fashion.
3) The abstract described the combination as additive to synergistic. Going by the monotherapy results (below) additive alone would be an additional 2.1 logs.
2 (naïve) 100 mg q8h 8 -1.7
4 (naïve) 200 mg q8h 8 -3.8
4) Not sure if you were pointing out the 500mg R7128 case to make a point but they will also test 200mg q8 191 with 1000mg R7128. There should be some additive (if not synergistic) benefit from the higher dose of R7128 as well.

I don't think the efficacy is plateauing at these low doses, although if that turns out to be the case I would think (longer down the road) room for adding a third or fourth antiviral is possible with these compounds. I would bet INFORM-2 or perhaps INFORM-3 at least tries adding Ribavirin to the mix and I think we could soon see an exploration of how prior non-responders (to interferon) do.

Based on this abstract (assuming no safety issues come up) I think if the highest cohort (200 q8 191 and 1000 BID 7128) doesn't get mean reductions in the mid 5's++ I would be disappointed.

I am surprised there hasn't been more discussion on the EASL abstracts (in general).