Replies to post #74854 on Biotech Values

[tony111]

Dewo,

I don't think Ribavirin will have a synergistic effect with direct antivirals in vivo since there was another drug designed to replace Ribavirin that showed enhanced Th1 response and limited direct antiviral effect in vitro like Ribavirin, but it failed the clinical trial. As you know many patients have an elevated ISGs before interferon treatment, people have speculated that having more interferon signaling in those patients actually triggers inhibitory pathways for ISG and therefore limits the efficacy of interferon. A recent study then tested the hypothesis to see whether Ribavirin suppresses the inhibitory pathway of ISGs after high dose of interferon and the data suggest its the case.

[DewDiligence]

Re: Role of interferon in HCV combination therapy

…preclinical data show that you only need interferon to prevent resistance to protease inhibitor…

I would respectfully submit that you’re misinterpreting the body of published research.

Protease inhibitors are not unique in this regard; rather, their differences from polymerase inhibitors in antiviral efficacy and in the speed at which they generate mutant strains are a matter of degree. Moreover, these two differences are two sides of the same coin; i.e. protease inhibitors stress the HCV virus to a greater degree than polymerase inhibitors, and this is why they generate mutant strains at a faster rate and are more susceptible to viral breakthrough than polymerase inhibitors.

Ideally, a cocktail of direct antiviral agents for HCV will include one or more agents that induce high viral stress and have a low barrier to resistance *and* one or more agents that induce low viral stress and have a high barrier to resistance. This approach has worked well in HIV, and the INFORM-1 study in HCV is starting down the same path. Regards, Dew

[tony111]

Too bad inform-1 does not have a 14+14 regimen. Otherwise we could compare the data with prove-3 to speculate on the role of interferon+ribavirin.