Everything you wanted to know about BMS-790052 resistance and pharmacokinetics, but were afraid to ask.

The ubiquitous Jules Levin posts slides giving a resistance overview of the highly touted BMS-790052 compound presented at the recent HCV Drug Resistance New Compounds Workshop in Boston, MA. See it all here: http://www.natap.org/2010/HCVresist/HCVresist_07.htm

So far, this is what we know:

* Once-daily NS5A Inhibitor
* Used in combo with P/R, there is an additive effect. Looks to be a good candidate for combination therapy as well - when used in combo with BMS NS5B inhibitor, BMS NS3 inhibitor and an unnamed nuc, there are both additive and synergistic effects.
* Blocks multiple stages of viral replication - inactivation of NS5A appears to take out a whole communication network between NS5A's, as they communicate with each other in a replication network.
* Nice correlation between in vitro and in vivo resistance. No surprises.
* Is there pre-existing resistance? Yep. Like the linear NS3 PIs, it appears that G1a virus are inherently more resistant to BMS-790052 than G1b. BMS suggests that "NS5A baseline sequences may provide useful information for predicting resistance emergence".
* Another big question for BMS-790052, as is for the other drugs in development, is drug interactions. As we've seen in HIV antiretroviral therapy, drug interactions are extremely important to know to prevent adverse events and fluctuations in pharmacokinetics that may compromise efficacy and lead to emergence of resistant virus.