From Briefing.com In Play:
07:24 VRTX Vertex Pharm: Believe that this new trial design is superior - Piper Jaffray (39.17 )
Piper Jaffray has recently learned new details that differ from their previous understanding of the upcoming Phase 2 trial for VX-950, Vertex's HCV protease inhibitor. Several sources have indicated to them that this 6-month dosing arm would include VX-950/PEG/RBV for 3 months, followed by PEG/RBV alone for an additional 3 months. Firm thinks this design alleviates the intensive focus investors have had on the timing of the completion of 6-month animal toxicity studies. Despite the change from their prior understanding, they believe that this new trial design is superior to the prior design because they believe the key to achieving superior sustained virologic response rates is predicated on the duration of PEG/RBV dosing. In particular, they believe there is compelling evidence to suggest VX-950 dosed for 3 months should induce undetectable HCV levels in a very high proportion of patients, and 3 months of additional PEG/RBV dosing would be used as "consolidation therapy" to generate very compelling S.V.R. rates.
Pharmacokinetic Boosting of VX-950, an Inhibitor of HCV Protease, By Co-Dosing With Ritonavir:
Background HCV protease inhibitors (PIs) are a promising new class of small-molecule, peptidomimetric HCV antivirals. In initial clinical studies, antiviral activity has been associated with HCV PI plasma trough concentrations. However, modest pharmocokinetics and the need for frequent dosing may limit their efficacy. (emphasis being added) CO-DOSING WITH RITONAIVIR (RTV), A POTENT INHIBITOR OF CYP3A, HAS PROVEN USEFUL FOR PHARMACOKINETIC ENHANCEMENT OF PETIDOMIMETRIC HIV PIs, WHICH ARE METABOLIZED BY THIS ENZYME. We investigated the in vitro and in vivo interaction of the HCV PI VX-950 with RTV.
Methods: Metabolism rates (disappearance of parent compound) were measured in pooled human (HLM) and rat (RLM) liver microsomes at an initial concentration of 1.0 uM PI and 0.5 mg/ml microsomes. Inhibition by 0.4 and 4 uM RTV was assessed. Sprague-Dawley rates were dosed with VX-950 at 5 mg/kg orally by gavage, alone or with 5 mg/kg of RTV.
Results: In HLM and RLM, 70% and 75% of VX-950 was consumed within 30 minutes (estimated in vitro t1/2 17 and 16 min, respectively). In the presence of 4 uM RTV, metabolism of VX-950 in both HLM and RLM was >98% inhibited. At 0.4 uM RTV, >70% inhibition was observed. In rats, PLASMA EXPOSURE OF VX-950 INCREASED BY >8-FOLD WITH RTV CO-DOSING. PLASMA LEVELS 8 HOURS AFTER DOSING INCREASED BY >50-FOLD.
Conclusions: The metabolism of VX-950 is strongly inhibited by concentrations of RTV achieved with boosting doses. CO-DOSING OF VX-950 WITH RTV IN HUMANS IS EXPECTED TO SUBSTANTIALLY INCREASE VX-950 PLASMA EXPOSURE AND TROUGH LEVELS, AND SHOULD BE STUDIED.
Bad news huh?
You have no credibility, you use what little knowledge you have to decieve. How pathetic.
Hard to believe that hasn't even tried a meaningful bounce yet. The it eventually will, but I think this speaks to how important that last neg. piece of news was.
Oh, on the cc, they mentioned that early tests they have conducted show that low dose ritonavir (sp?) has been shown to increase the concentrations of 950, and will be explored later, but will not alter the trial timeline. I had read an abstract on that some time ago.
stymie, I don't know if you heard the call, but they did talk about amount of drug available, and what their capacity will be by the end of the year, etc. I don't remember the numbers, I had other things going on.
hmm.....didn't you say they couldn't dose past 14 days because of rapid viral resistance? Then, didn't you say they couldn't go past 28 days? Didn't you also say they would never get to phase 2? (you didn't count the first one, it wasn't as big as IDIX's).
Moving those goal posts.....
You are like the law firm of Dewey, Cheatam, and Howe.
If you can win by aruging the facts, you argue the facts (not your strength)
If you canwin by arguing the procedure, you argue the procedure.
If you can't win, YOU JUST ARGUE! LOL
You must get paid very well to spout meaningless nonsense every morning in an effort to flame and distort. How's that 800 mg arm of 283? How's the stock?
I didn't get to hear much, but it seems (don't know if it was mentioned) instead of doing 3 smaller trials, they are doing 1 bigger one instead, which probably makes sense. They are evaluating the full range in this one, instead of in different ones, but we already knew many of the arms. We knew they would test a mono arm this year, we knew about the different lengths of arms since last week, and also the non-responders. I said a while back that this trial was getting started a little later than previously thought, so our expectations for beginning p3 were based on that. They had said 2007, so now they narrowed it down, and are still on track for 2008 NDA.
The 2 new things off hand that stuck out as being "new" news was the size of the trial being much larger, and they spelled out how much drug they had and the manufacturing of it.