Biotech Values

[iwfal]

ribavirin does show good synergy in the replicon with interferon, so it would be nice to show similar synergy with the DAA(s) in question before moving to combo without interferon in the clinic

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First, you are right that I was unclear - my intent in saying the preclinical models were poor for immune mediated responses was talking about long term systemic effect. I had totally forgotten about the fact that ifn does have direct cell mediated effects and ribavirin does have some direct anti-viral effect, both of which can be modeled in a replicon system.

Thus the replicon model does show some of the efficacy of ifn and rib - but I contend it doesn't really show the long term synergy where on a log scale addition of rib to ifn knocks viral count down another log or two (I don't remember the numbers offhand) after months on treatment. But in the replicon model (see below cite) it only adds a miniscule addition to ifn (on a log scale).

http://jcm.asm.org/cgi/content/abstract/43/11/5679

PS Note that I am a little weak on the theory and capabilities of a replicon model - so it is possible that I was looking in the wrong models, ... . But my impression in a long ago review looking for this synergy in a replicon model was that it was not captured in the model.