Maybe you missed my point about VRTX triple therapy with Incivek, VX-222 and Riba. My feeling is Riba in the absence of interferon won't provide a strong enough resistance profile to prevent viral breakthrough with this combo.
If there are any additive effects to including Riba to PSI-7977 they allude me. It won't boost efficacy or the resistance profile over monotherapy and it will only cause tolerability issues and will require BID dosing. My guess is VRUS wants PSI-7977 to be the backbone of all future oral therapy. PSI-7977/Riba should be the the first oral offering to reach the market maybe followed by 7977/BMS-790052, 7977/TMC-435, etc. Perhaps VRUS management feels they can create greater shareholder value working with the competition as opposed to competing on their own with monotherapy? Maybe they plan to drop the Riba if another company comes to market with a two drug oral combo which doesn't use PSI-7977 as a backbone? Maybe the FDA required Riba because old habits are hard to break? In the last C.C. VRUS management made a case to analysts for including Riba in the late stage studies but I personally don't see a need for such a weak, redundant drug with PSI-7977.
Vnfin, please explain why you think Pharmasset is including ribavirin in all their upcoming all-oral trials directed against genotypes 1,2 and 3. Why not just go with monotherapy using PSI-7977 if it is potent enough to do the job against all three genotypes? That would certainly be more impressive. Why does it "appease the FDA", as you put it, to include ribavirin in their trials? Apparently, what you are saying is that Vertex needs ribavirin to improve their chance of success in all-oral hep C regimens but Pharmasset needs ribavirin to appease the FDA.
"No matter how much you inhibit viral replication, proper treatment for HCV will likely always include something that boosts the immune system."
Your argument here is supportive of interferon based therapy which is being phased out. The marriage of Peg/Riba worked because the weak nucleoside (Riba) needed an immune system booster (interferon) to optimize its efficacy. Riba provided limited anti-viral properties and a strong resistance profile.
Those days are over. It is essential for an anti-viral to knock the virus down quickly which PSI-7977 does. Within two weeks viral loads are below the LOD in over 90% of patients and the body's immune system cleans up without interferon boosting.
HCV nucleoside analogs are targeted RNA chain-terminators which halt replication. You seem to have transposed the abilities of interferon and ribavirin in your post.
Keep repeating it, but that you call everyone "oudated" because you already know the results of a future trial as already (in your mind) succesful against gt1 is a mantra, but it is not reality. So keep your OM, but you do not have any hard data. If they published it tonight or tomorrow, congratulations.
Ribavirin is a nucleoside analogue. It stimulates the T cells in the body to fight the virus.
Interferon attacks the virus by interfering with its ability to copy itself and spread throughout the body. Interferons are proteins produced by the cells of the immune system that prevent viral replication.
So the MO for the HCV SOC is, in layman's terms, stimulate the immune system to fight the virus and inhibit the virus's ability to replicate itself. Kill what is there and keep it from growing.
And the last I checked, PSI-7997 was a nucleotide polymerase inhibitor, and PSI-938 is a nucleotide analog polymerase inhibitor... again the idea is to prevent viral replication.
HCV is hard to treat because it mutates. To prevent mutation, you have to kill the virus quickly. No matter how much you inhibit viral replication, proper treatment for HCV will likely always include something that boosts the immune system.
Therefore, I am open to correction here... but that said, I don't see Ribavirin going away in the near future.
Important to read how they sell the trials. You can get a real sense of the excitement, however-hyped. Terrific job of stressing the first all-oral phase3 instead of the throw in gen 2,3 for the first 2 trials and a few gen 1 for the final depending on phase2 results.
This is why VRUS is $70 and VRTX is $36. If this management team were running Vertex it would be $100/share.
There's many reasons to believe arm E+F will be susceptible to viral breakthrough. Ribavirin is a weak 30 year old nucleoside and I question its usefulness even in combination with PSI-7977. If Riba was the answer don't you think JNJ would be testing their late stage protease with it? Or BMY with their NS5A?
I agree we should let the future data decide who is right on this issue. The phase 2 GT1 oral studies being run by VRUS are being matched by VRTX with their ongoing phase 2 oral studies in arms e and f of the Zenith study. Results of arms e and f of the Zenith study (all oral 400 mg VX-222/Incivek/ribavirin) study will be available in early 2012.