Firstly, I want to thank TheDonald and JustLooking for encouraging me to come on over to the VRTX board. I'm looking forward to pissing on the VRTX HCV "drug" (giggle) as they have so feebnly tried to do with valopicitabine.
So let's get this party started...
You're so hot on your 14-day response? (giggle again). This look familiar:
The BILN cpd showed a 3-log drop after only TWO doses! IMPRESSIVE, huh? Setting the tox stake-in-the-heart aside for a moment, look at all the resistance mutations that popped up in that very short time. Hmmmmm? There's ALREADY evidence that the VX950 is heading down that same path. Come back when to have an SVR figure - OK, I'll settle for 12-week data (incessant giggling).
This seems to indicate that VX 950 retains its potency against mutatated virons, don't you agree? Quotation marks are mine.
In this report, they describe resistance studies, using an in vitro replicon system, conducted on VX-950 and BILN-2061, another HCV protease inhibitor, which was recently reported to be in clinical trials."
Distinct drug-resistant mutations were identified for both protease inhibitors. "Mutants that are resistant to BILN-2061 remain fully sensitive to VX-950."
>>Distinct drug-resistant mutations were identified for both protease inhibitors. "Mutants that are resistant to BILN-2061 remain fully sensitive to VX-950.<<
I did the same thing, but in reality it works vice versa. After the comma it states that IDIX's drug overcomes a VX-950 weakness.
I do have access, thanks. Good to hear that SAR is still the meat-and-potatoes of R&D, but what are they going to do with all that fancy molecular modeling stuff? Oh well - looks good for the analysts visits maybe.
>>Firstly, I want to thank TheDonald and JustLooking for encouraging me to come on over to the VRTX board. I'm looking forward to pissing on the VRTX HCV "drug" (giggle) as they have so feebnly tried to do with valopicitabine.<<
>>yeah, and here's what comes after the comma, you phoney sack of sh1t:<<
What's the matter tough guy. Got your panties in a wod? Why don't you get lost A$$hole. I made a honest mistake and you had to go and start name calling. Why didn't you finish with the rest of your link and let the truth stand? Both drugs have resistance problems.
>>VX-950 at Ala(156) remains sensitive to BILN 2061. Modeling analysis suggests that there are different mechanisms of resistance to VX-950 and BILN 2061.<<
You're a moron. Now you get lost. You take a MB so sensitively. What do you do in real life when someone cuts you off in traffic. Get heart palpatations? lol
I asked you for some data regarding HCV becoming resistant to PI's. That proved there wasn't any hard data IMO. I called you on it and you got pissed off.
Ahhhh...so that's quite a bit different that "no resistance" for VX950, isn't it? I posted the WHOLE link - you cherry-picked the half-a-sentence you liked - simple as that.
You keep your peabrain 2 cents off the IDIX board, and I'd be happy to go back peacefully. Otherwise...you're just gonna have to get used to me - I'm startin' to like it over here.
Welcome to the party! Your link does show some impressive data and I am surely no expert although I do have first-hand experience with current HCV therapy. What I don't like about the data that is presented is that it appears from the following 2 statements that this drug may be too specific at certain areas in the RNA strand that are not as broad-based as one would like:
Individuals with genotype 2A and C tended to be responders, while those with 2B were poor responders.
Similarly, individuals with 3A were poor responders while those with 3B were more likely to respond.
Currently, ALL 2's and 3's are the easiest to treat with today's treatment (INF and Ribaviron). I had 2B, did 5.5 months of treatment 3 years ago and am still negative!
This drug may encourage mutations because it inhibits a protein that has to do with the mutation process and not the basic replication process. Since you may be attacking a protein that causes mutation only, it would probably be an easy thing for HCV to mutate out of the way since the basic replication process isn't inhibited as much as one would like. But who knows, this may be a good canditate for a combo treatment!
I have not seen any genotype specific data from VX-950 except for the fact that all patients on the VX-950 testing were Genotype-1. If you have any data about possible mutations from VX-950, please post it so we all can read it.
Both the VRTX and BILN drugs target the HCV NS3 protease, presumably at or near the active site of the enzyme. This enzyme is required to process a number of the non-structural proteins required by the virus. The amino acide sequence of the NS3, especially within the active site if *fairly* constant within a given genotype, but differs more so between genotypes (see below).
This could explain the selectivity (i.e., VX might work better against some genotypes than others), although I have not yet seen any data on this. If the VX drug is that "picky," it could also explain why single amino acid changes, like the one decribed below, might be enough to cause resistance.
VRTX did some nice work in elucidating the crystal structure of the HCV NS3 protease, probably about 10 years ago, if memory serves. That led to molecular modeling, which presumably led to VX950 (about time). Anyway, the structure of the BILN drug has been published - I have not seen the structure of VX950, but I'm guessing that it's not much different.
Its pretty clear the VX inhibitor is speculative until further testing confirms efficacy. Its also pretty clear that larger scale trials are needed to assure there are no other unwanted inhibitor actions.
So place your bet.
What makes this company worthwhile is the generally healthy cash flow, based on associations with some big pharma companies, that should keep the research engines pumping while the formulations are evaluated.
I'm in long, lets see what happens. Biotech is like Vegas, only wager what you can afford to lose.... but if you don't play, you can't win.