[>there is nothing in the works as a telaprevir backup<]
This is an answer to the question Matthew asked earlier.
At the time Vertex announced the acquisition of VCH-222 in early 2009, Vertex was developing two novel HCV protease inhibitors (=PIs), VX-813 and VX-985, which were in Phase 1 and preclinical development respectively in 2009. The landscape for the drug development has since changed radically. Not only competing first generation PIs such as TMC435, BI 201335, or ACH-1625 completed or in the process of completing Ph 2 clinical trials, but also a second generation PI led by Merck’s MK-5172 is in a Ph 1 trial. The latter compound does not seem to have “cross-resistance” issues with other PIs and might be effective across multiple HCV geno-types [the following NATURE’s Supplemental article is sponsored by Gilead and Merck]:
In addition, nucleotide analog polymerase inhibitors led by PSI-7977 and NS5A inhibitors like BMS-052 showed great promise.
The above NATURE article appeared a month ago lists VX-985 as a PI being developed for Ph 1. However, it is not difficult to see that Vertex would develop VX-985 through a Ph 2 clinical trial and beyond only if it is better than Telaprevir AND MK-5172 in safety and/or efficacy because it knows how expensive to develop a PI through trials and these two PIs set up a high bar for a new PI. (If it develops polymerase inhibitors, they should be better than 7977 in safety or efficacy. I know that Vertex is working on NS5A inhibitor, but it makes little sense to announce it unless it is better than or equivalent to BMS-052.)
So, I think Vertex has had backup or novel compounds they have been testing, but it has not YET announced them for the above reasons OR the testing has not been completed. This contrasts Gilead’s approach which lists its Ph 1 compounds.
"So, I think Vertex has had backup or novel compounds they have been testing, but it has not YET announced them for the above reasons OR the testing has not been completed"
OR, these two compounds have been tested, found to be significantly lacking and while VRTX has not made it official in their annual report or a press release, they are no longer going to be developed.
Someone asked me earlier what it is that I was trying to say in my original post and I seemed to be answering my own question. Now that I think about it, that is correct. I was merely venting at the lack of productivity from VRTX research in the HCV area. Just wondered if anyone else felt the same thing. I did not realize that I was in fact answering my own question :-)
It may not be wise to mobilize human resources for developing a 2nd generation PI. Incivek can compete well against any first generation drugs such as TMC435 or ACH1625 in both safety and efficacy, and it will do well even against 2nd generation PIs for the interferon responsive AND tolerant patients such as ones with the IL28B C/C allele since the SVR rate for the latter group is 90% when treated with an Incivek based combination therapy. As you may know already, the active sites of HCV NS3/4A protease form shallow pockets and it is difficult to develop an inhibitor against them.
A far-better strategy is to combine a PI with non-nuc and/or nucleotide analog polymerase inhibitors because these inhibitors can terminate the viral synthesis very effectively. Only concern with nucleotide analogs is that they can be mutagenic.
By in-licensing ALS-2200 and ALS-2158 from Alios, Vertex must have taken the strategy that (1) develop all oral DAA combo for interferon non-responsive or intolerant patients, and (2) shorten the treatment duration to 4~8 wks for interferon-responsive groups. There are paramount reasons to shorten the treatment time and to remove Ribavirin from the mix. This cannot be done with protease inhibitors alone.