Biotech Values

[nivasvs]

IDIX-It’s only in-vitro data, but it could nevertheless give an early read as to whether a cocktail of drugs from the three main classes will provide additive or even synergistic activity

You got what you've wished for. The results indicated either very good additive effect or synergistic effect, whichever way you want to call it.

From abstract submitted to EASL:

http://www.kenes.com/easl2010/Posters/Abstract657.htm

Results: In standard assays in the genotype 1b HCV replicon system, the EC50 values of the single agents were 106 nM (IDX184), 2.3 nM (IDX375) and 0.5 nM (IDX320). Double combinations of IDX184 with IDX375 or IDX320 showed additive antiviral activity in vitro compared to treatment with single agents. In 14-day treatments of replicon cells, the single agents at concentrations of 450 nM (IDX184), 15 nM (IDX375) and 1 nM (IDX320) generated reductions in HCV replicon RNA between 0.7 and 1.6 log10. All double combinations resulted in replicon RNA reductions of 2.0 to 2.6 log10, consistent with an additive antiviral effect. However, 14-day treatments with triple DAA combinations (IDX184, IDX375 and IDX320) resulted in RNA reductions of almost 4 log10, substantially higher than the expected additive effect. Outgrowth of these treated cells in the presence of G418 resulted in an average of < 5 replicon-bearing colonies remaining (frequency, < 0.01%), indicating that most of the replicons had been cleared by triple DAA combination treatment.

Conclusion: These studies suggest that a triple combination of IDX184 with direct-acting antivirals from different classes, such as IDX375 (NNI) and IDX320 (PI), can lead to significantly enhanced suppression of HCV in vitro compared to single agents or double combinations. This effect, coupled with the different resistance profiles of the three agents, suggests the potential value of triple combination regimens in future HCV clinical studies.