vx-950

[da399]

i wished someone could please tell me vx-950 is ready to market. i have hep c, geno type 3, have been thru 2 treatments already. my virul levels are on the rise again, doc says it's time to go back on treatments, but they make me so sick i'm afraid i can't take care of my kids properly. i am a single parent. i have been praying for something new w/ fewer side effects.

[charm27]

From what I was told from my hepatologist it would be approximately 6-7 years. The reason being the FDA approval takes quite a bit of time.

Hoping its sooner.

[fightit]

VL's go up and down, and they are not the best indicator of when to go on treatment. Your biopsy will give you more information so you can make an informed decision. Have you had a biopsy lately, and what were the results.
Everyone is guessing about when and if vx-950 will hit the market. The truth is nobody knows. Some say if everything goes well it could be on the market by 2010. It is still in trials so if you have considerable liver damage you may want to see about getting in one. Depending on your bx results you may have time to wait.

It's hard to take care of yourself on treatment much less others. I don't know how old your children are but if they are old enough they could help out a lot around the house. Of course if you are talking about the mental stuff that goes on, it can be very hard to be a kind, loving, sweet parent, when you feel as lousy as you do on tx. Even though you can explain it to people they don't really understand what you are going through.
If I were you I would want a little more information before I went back on treatment. I wish you the best in whatever you decide.

[copyman]

a top hepatologist told me by 2011. the FDA is not appoving dugs as fast as they use to because of recent drugs that were fast tracked and had to be pulled off maket due to adverse effects. Have you considered a trial with one of the new drugs for relapsers/non responders? this is the only way you will get VX-950 or any other new drug sooner then a few more years. good luck

[3txsofar]

Since the estimates of VX-950 were quite pessimistic, I should give the optimistic time.  Assuming the Phase III starts in early 2008, it could be approved in 2009.

[Willy50]

No one truely know since the evaluation time will be based on the results.  Phase 2 is still ongoing and Phase 3 has not yet started.  IF things go well it will be less time.  If things go poorly it could take longer to evaluate the information presented.  So far, the results of Prove 2 seem to be coming in line with Prove 1 and there have not seemed to be any new concerns or differences in results.  This is good news since ambiguities may pose evaluation issues as large as negatives. (such as the rash)

It looks as if Phase 3 may not start this year; that would count for one delay.  Other possibility/likelihoods are that;

1) Phase 3 trials may be larger and therefore take more time to fill and therefore complete.

2) The Phase 3 VERTEX triple therapy trials will likely only have a duration of (12&12) 24 weeks with a 6 month wait for an "official" SVR; that's about 1 year from the time for ALL participants start and finish.  Since the trial also must include a control arm that suggests a 48 week SOC arm and the required 6 month wait EOT.  Therefore the trial end cannot come for a minimum of one and a half years after ALL participants end the trial and recieve 6 month post treatment data.  It doesn't seem out of the question to figure that the Phase 3 trial could take 1 3/4 to 2 years to complete.  Therefore Vertex may not be able to provide the FDA with the final data from the Phase 3 trial until the end of 2009 and quite possibly sometime in 2010.

No one can predict what the FDA will require or how long it will take since it hinges in part on the trial results.  Vertex won't comment on that.   Right now they are still waiting on the design and go ahead on starting the Phase 3 trials.  They can only go as fast as the FDA guidelines will allow.  The FDA has been under some recent pressure about approving drugs too fast such as Vioxx.

The bottom line is that no one really knows.  Any number will be a bit of a guess.  I think it would be impossible for it to occur in less than 2 1/2 to 3 years, though.  That kind of lines up with the 2011 prediction assuming no problems.

best,
willy

[3txsofar]

I'll stick with my 2009 forecast.

I think the results can be submitted to the FDA roughly 12 months after the last enrolee, not 18.  The reason is simple.  All patients will have finished treatment and the telaprevir arms will have their SVR data, while the control will only have EOT.  But the control will not improve as it goes to SVR it will only get worse and everyone including the FDA knows that.  On top of that , you will have complete side effect information. Of course, I am assuming that the telaprevir SVR numbers will beat the control EOT.

But, I'll stick with my forecast of 2009 based on Phase III.

Happy Holidays to all.

[Willy50]

Hey, I like the sound of your prediction much better.  : )

Vertex won't go out on a limb and predict what the FDA will do.  To some extent we are still only about 5/8's thru the ball game (the trial).  Still a lot can happen.

A large unknown is how much time the FDA will take to evaluate the drug following the trials end.  They've come under fire for approving unsafe drugs before.  There is no question that if they can get it approved sooner that many lives will be saved.  That could also weigh in on their decision.

best,
Willy

[Proactive]

I actually thought your timeline was well thought out, and pretty darn realistic..I'd say early 2011 best case..Hope all is well...Hey, today is the first day of my last 12 weeks of 72 weeks of tx...^)

[CJ807]

Is this just wishful thinking now?  On the market in 09...come on you 09'ners


"The initiation of Phase 3 clinical development with telaprevir is our
primary objective for 2007. We anticipate that information derived from the
PROVE program and other studies will support the design and initiation of a
Phase 3 program," continued Dr. Boger. "More broadly, we are building our
capabilities and adding expertise in key areas--clinical development,
regulatory affairs, quality control, supply chain management, and
commercial development--designed to support an NDA filing in 2008."

Everything looks on track, does it not?

[mremeet]

Yes it does look on track. I think it could fairly easily come to market within 2 years, not 3 or 4 years. But yes, anything's possible. Yes the FDA is gun shy now (and hence sluggish), and no there are no guarantees. But hundreds and hundreds of people have taken VX950 at this point (including myself), and it works. Sure it has side effects, I got the worst of them (the dreaded uber rash), but it's a workable drug and it WORKS at kicking viral a$$. With any luck, hope, and sense on the FDA's behalf, telaprevir will be available for sale/use by late 2009 early 2010. Could I be wrong? Sure, but remember late 2009 is two years from now. A lot can happen within that timeframe, and telaprevir is going into its final phase of trials now, and enrollment will be moving right along very soon (if it hasn't already). Considering that the likely average timeframe for tx (for phase 3) will probably be 24-48 weeks, add into that another 24 weeks for SVR data to come in and where does that put things? Remember that telaprevir *is* fast tracked, and that every single phase 3 SVR datum point need not be in prior to FDA approval. Bottom line is that there are no guarantees, but telaprevir could very well be available prior to 2011 or 2012. Plus, geez, just the sound of "2011" or "2012" makes me feel old. ;-)

[Willy50]

".Hey, today is the first day of my last 12 weeks of 72 weeks of tx...^) "

Congrats and I hope that the last 12 weeks are uneventful and smooth for you.  Man, you are a marathoner.  Best wishes for you in the upcoming year.


The last few things that I've heard regarding the quote used above from Josh Boger have changed mildly.  There was the supposition that the Phase 3 trials would start in late 2007 (which they have not yet at the time of this writing).  T

They also hoped (hoped, but not predicted) that the trial data could be used when the VX arms ended; not when the control arms ended with the 6 month PCR's.  I must admit, I don't fully comprehend the purpose of delaying a trial or a NDA filing over the results of an SOC control arm.  There is a 6 month difference between the VX triple therapy arm and the SOC arm (presumably; we don't know the shape and appearence of the trials yet).  How many people will die from HCV and liver failure in 6 months?  Do they really need to have the SOC (control arm) results?  One would suppose that at this time the stats for SOC should already be well known.  It does make for a proper trial and crisp clear stats but they need to consider that many peoples lives hang in the balance.

There is yet a third possibilty and that is that the FDA could impose a longer triple therapy arm to see if more people could clear.  Even if this were the case is seems unlikely that it could be any longer than the SOC arm.  However, IF they were allowed to file an NDA before the results of the SOC control arm were finished THEN a longer VX trial arm could conceivably slow the trial a bit.  

I'm very excited about the prospects of the Phase 3 trial starting soon.  It begins to look as though January could be the month or the month that we hear about the latest plans.  If I recall correctly we may also have a batch of some Prove 3's who will have been of TX for 12 plus weeks and we may get an update on that as well during..... I think there is a medical conference in Jan or early Feb.

best,
willy

[CJ807]

How often does it have to proven that SOC SVR is 50%? Ridiculous (now I'm an expert on trial assy)! Maybe with a new interferon of course. But a fastracked protease inhibitor? Get 3000 hereos and lets move on!

Did I once hear that it may be possible to phase III w/o SOC control arm based on past results and involving rescue drugs? Might of been something else or somebodies wish.

[APKhaos]

My Prove 1 clinic is participating in the Phase 3 trial, and preparing to start in January. The trail design is in final stages of FDA approval, and they are registering subjects ready for screening as soon as the flag drops. This clinic tends to be among the very early starters for each of the Vertex trials.

[Willy50]

Your first question is rhetorical.  I don't know exactly how much the control arm actually ends up affecting the consideration and ultimate approval time.  If the data gets forwarded before the trial were to end the FDA can still be considering the VX data even while the SOC control arm is winding down.  I can't speak to the ultimate effect in the approval time.  If there IS a delay in approval time one could very well also express it hypothetically in a number of people who will not be able to treat and therefore face transplantation or death.  In a year that could be a lot of people.

I've never heard of Vertex speak of NOT having a control arm in Phase 3.  They won't comment on what may comprise a Phase 3 trials.  The only thing I've heard them confirm (by webcast) is that there WILL BE a control arm and a "12 &12".

They have spoken also that the FDA wants RESULTS in the Phase 3 trials-CURES.  This leads me to suspect that there could be rescue drugs allowed during the Phase 3 trials although no one I've heard has said so.  I'm guilty of having written wondering if it could happen.  It is certainly my wish.

This is also an area that I don't understand.  WHY has Vertex not allowed rescue drugs while the Boceprevir (Scherring-Plough compound) trial allowed them (or so I have heard).  At first I had thought that they simply were forbidden in trials.  IF it is up to the company running the trial why has Vertex decided (at least up till now) to not use them?  I don't have any answers but am very interested to see what Phase 3 will bring.  

best,
willy

[Willy50]

Thanks, our posts crossed.  That is great to hear.  I was going to call my local hospital today and see if there was a chance that an expanded trial could include them.  IF so..... I'd probably jump at the chance.  It probably won't happen though.  (I may have to move.  : ) )

Great to see that you, MREmeet, PLN and so many others were able to clear and attain the SVR.  Thanks to you all for keeping us up to date on things along the way.

best
Willy

[Bill200]

How does that work?  What is the purpose of the Prove 1 participating in Prove 3?  Is it for the prove 1 patients who didn't clear?

regards, David

[APKhaos]

Many, if not all, of the clinics that were participating in Prove 1 are also participating in Prove 3. Its the clinics, not the subjects.

In fact, the expectation is that Prove 3 will be for treatment naive subjects which would disqualify anyone who had been in a prior Vertex trial. We won't know for sure until the study design is published, but its a good bet that it will be that way.

[Susie2007]

If you had trouble with side effects of interferon and ribavirin, you will have the same problems again as VX950 will need to be used with both those drugs. Telaprevir as a monotherapy does not work.

[Bill200]

What about an estimate for previously treated (non-responder SOC)  patients?  What's your take on when vx950 trials for that situation more start?

regards, David

[geterdone]

Pharmasset looks like they have a very promising drug in the pipe line but looks like it will be some time before it hits the market.

jasper

http://www.pharmasset.com/pipeline/psi-6130.asp

R7128 is being developed by Pharmasset and Roche through our collaboration to develop nucleoside polymerase inhibitors for the treatment of chronic hepatitis C virus (HCV) infections. R7128 is a pro-drug of a molecule we discovered named PSI-6130, an oral cytidine nucleoside analog. PSI-6130 is the active component of R7128. At low concentrations, PSI-6130 was shown to be an inhibitor of HCV replication, specifically targeting the HCV RNA polymerase. In preclinical studies, no toxicity was observed in various human cells, including liver cells, bone marrow cells, and white blood cells. When compared in laboratory studies to several other compounds in development for the treatment of HCV, PSI-6130 was found to be more active at low concentrations and/or less toxic. In combination with interferon, PSI-6130 was active and additive to the activity of interferon alone in these preclinical assays.

In October 2006, Roche and we initiated oral dosing of R7128 in a Phase 1 clinical trial under an IND. This trial is a multiple center, observer-blinded, randomized and placebo controlled study designed to assess the pharmacokinetics, pharmacodynamics, safety, tolerability and food effect of R7128 in healthy volunteers and in patients chronically infected with HCV genotype 1, as well as provide antiviral potency data over 14 days in patients chronically infected with HCV genotype 1. This study will be comprised of two parts:

• Part 1 is a single ascending dose study being conducted in up to 38 healthy volunteers. The primary objective of Part 1 is to assess the safety, tolerability and pharmacokinetics of R7128 following single ascending doses under fasting conditions. The secondary objective of Part 1 is to explore the effect of food on the pharmacokinetics of R7128.

• Part 2 is a multiple ascending dose study being conducted in up to 40 patients chronically infected with HCV genotype 1. The primary objective of Part 2 is to assess the safety, tolerability and pharmacokinetics of R7128 in patients chronically infected with HCV genotype 1 after once-daily or twice-daily dosing for 14 days. The secondary objective is to assess antiviral efficacy by measuring the decrease in HCV viral load.
Roche and we recently completed dosing 38 healthy volunteers with R7128 in Part 1 of this study, which included a food effect cohort. Preliminary safety and pharmacokinetic data supported progression of R7128 to Part 2 of this study in February 2007 and also indicate:

• All doses of R7128 were generally well-tolerated in single-dose oral administration.

• No abnormalities of clinical significance were noted in studies of hematology, an indicator of bone marrow function, and chemistry parameters, an indicator of kidney and liver function.

• All subjects completed Part 1 of this study, and no subject experienced gastrointestinal adverse events or a serious adverse event during the study.
In November 2005, Roche and we conducted a single ascending-dose, randomized, blinded study of PSI-6130 outside of the United States in healthy volunteers. The study evaluated the safety, tolerability, and pharmacokinetics of sequential ascending levels of single doses of PSI-6130, as compared with placebo. A total of 24 subjects were enrolled in three sequential dose groups with eight subjects per group (six subjects assigned to PSI-6130, two subjects assigned to placebo). In this completed clinical study, single oral doses of PSI-6130 were generally well tolerated with no serious adverse events in doses up to 3,000 mg and achieved bioavailability and pharmacokinetic properties that may be associated with antiviral activity in people infected with HCV.

[FullOfHope77]

Assuming we are able to SVR I'm starting to thiink about what up and coming on 'healing' our livers as well and that means to reverse the scarring process including cirhossis that many don't believe is possible. This was passed to me today and was curious if anyone has see or heard of this or other type drugs that are 'in process' to assist in this... here's the link:
http://www.guardian.co.uk/science/2007/dec/27/medicalresearch.drugs?gusrc=rss&feed=11

Thanks,

scotty

[burned74]

here is a nice chart showing all the hep c drugs and phases of development that they are in. its updated about once a month or so

http://www.hcvadvocate.org/hepatitis/hepC/HCVDrugs.html

[Proactive]

Just saw on CNBC that Wachovia downgraded Vertex...price target $14-$17.......but more importantly, citing no fda approval for vx950 until 2012 (they were at 2010)...can't find any hardcopy of the news yet, but I'm searching....just a 7:00 AM headsup......pro