Biotech Values

[DewDiligence]

Re: Future HCV therapy

I was curious if people thought future regiments are likely to have multiple agents in the same class (e.g. 2+ polymerases, 2+ NS3/4 proteases) or is likely to turn out that a more effective regime will be several different mechanism (e.g. protease, polymerase, helicase and maybe even Ribavirin).

The various classes of HCV drugs are abstractions that ought not to be taken too literally.

For instance, there are at least two distinct binding sites on the HCV polymerase (the “thumb” and the “palm”) employed by existing drugs in the non-nuke class. It could turn out that two non-nukes are additive or even synergistic by binding to different sites.

Similarly, nukes can be either purine analogs or pyrimidine analogs. Two nukes—one from column A and one from column B—can be additive or synergistic with each other. (This was the scientific impetus for Truvada!)

Among the three commonly recognized classes—nukes, non-nukes, and protease inhibitors—PI’s probably have the least opportunity for two or more drugs from the same class to be additive or synergistic. (Notably, there are no approved HIV regimens that include multiple PI’s as therapeutic agents, although ritonavir is often used with another PI as a pharmacokinetic booster.)