"Opko Health's bevasiranib, a naked siRNA targeting vascular endothelial growth factor for age-related macular degeneration (AMD), was on track to become the first FDA-approved siRNA therapeutic.
The drug had ridden into Phase 3 trials on the basis of animal data indicating it could block the subretinal vascularization that causes blindness in AMD. But those studies used a transfection reagent not used in the human trials. Ambati's results suggested the drug's efficacy had nothing to do with RNAi, but rather with an innate immune reaction to double-stranded RNAs mediated by the Toll-like receptor-3 (TLR3).
Ambati says the findings are not terribly surprising; researchers knew that in general, cells don't take up naked siRNA. "It seems to me that there was an irrational exuberance about the technology, and to be frank, the science behind these [original bevasiranib animal studies] is not sound and contradicts very good science showing that double-stranded siRNAs don't get into cells."
That perception seemed vindicated March 6 when Opko Health, citing the recommendation of its Independent Data Monitoring Committee, announced it was terminating its Phase 3 trial of bevasiranib because "the trial, as structured, was unlikely to meet its primary end point."
October 2009 -- Science Magazine
Sentiment: Strong Sell