Finally. The Vertex Trial Information We've Been Waiting For.

[jmjm530]

First, I want to thank Milked for bringing these trials to our attention in his post below and apologize for the redundancy -- but because this release has so much meat to it, I thought another thread might be warranted both because of additioanl discussion and because it flags the trial aspect of the process.

I urge everyone who has something at stake to take the time and read the full release here http://www.vpharm.com/Pressreleases2006/pr052306.html

But to summarize very roughly (and hopefully someone else will do a more complete summary)

1. Vertex is starting a Prove I trial study in the United States with first dosing of patients to occur this June.

The study group will be broken down as follows.

A. 12 weeks with Vertex in combo with Peg and Riba
B. 24 weeks with Vertex  in comobo with Peg and Riba
C. 12 weeks with Vertex in combo with Peg and riba followed by 36 weeks of just Peg and riba (48 week total)
D. Control arm with Peg and Riba (no Vertex) for 48 weeks

2. In the second half of the year, Vertex plans to initiate a Phase IIb study in patients who failed prior standard of care treatment.

Again, the link for the entire release is here:
http://www.vpharm.com/Pressreleases2006/pr052306.html

[jmjm530]

We've had this discussion before and I've heard otherwise, plus  it would seem that if we relied on the naked immune system alone to hold onto SVR, than SVR would not be as durable as studies show it to be. Still, I'm taking pretty d*mn good care of myself right now just in case you're correct. LOL. Must admit I did not follow your Vertex analogy but mind is a bit foggy lately.

[GoofyDad]

Dunno whether you'll see this way down here.

To continue the PI 4-week discussion, I guess it comes back to the question of whether we rely on our naked immune system to support SVR once therapy is withdrawn. It seems more and more evidence points in that direction. If that is in fact the case, then I would propose that by acheiving RVR aided with vx-950 your immune system has made as compeling a demonstration of its ability to fight the virus as it would be acheivng RVR unassisted by vx-950.  

On the other hand, if VX-950 obliterates the virus completely, well of course that would be goodness in its purest form.

[jmjm530]

Yes, if all goes as planned they file in 2008 which I guess means going to market potentially in 2009.

However, on the webcast, one of the analyst questioners asked if the process could be speeded up, assuming the Phase II go extremely well, possibly even abbreviating the Phase III aspect.  

I got the sense that Boger (didn't realize he was talking) hedged a little before answering. Wasn't sure if that was because a speedier  filing was his hope as well,  and he was playing it close to the vest because of FDA and other concerns -- or, if that's simply not in the cards. But knowing Boger's agressive reputation, wouldn't be surprised if they make an earlier move if given the opportunity.

Still, from risk/reward analysis of those treating --  right now, 2009 sounds about right if the trials prove out. However, there should be a number of opportunites available for selected folks in the phase III trials projected to begin in mid 2007. Hopefully, they will have dropped the Vertex placebo arm by then, so presumably everyone will get Vertex for at least 12 weeks, with the difference being in how long they treat after peg and riba. In Europe, there is a planned arm without the riba.  

-- Jim

[mikesimon]

I hope that I haven't given the impression that I don't want Vertex on the market as soon as possible because I sure do. It's the most exciting prospect I've seen since I've been in this quagmire called hep c. I just haven't seen any indication that it would be available as soon as BB has postulated. I think he said 2006 or 2007 and I was worried that people might base their decision to treat or not on that time frame, which I still think is totally unrealistic. But, if it could be brought to market earlier and safely I'm all for it. But really, I think 2009 sounds about right.  Mike

[jmjm530]

From ways back, you've always impressed me as one of the big fans of Vertex's potential. I agree with your realistic assessment on dates, and of course we all hope they can do better in a safe manner.

[mikesimon]

Boger said the earliest Vertex could probably file to have VX-950 approved would be in 2008. He said the company still hopes to have the drug on the market in 2009.

Boger is Vertex CEO. Mike

[jmjm530]

RVR is the name of the game with the new protease inhibitors. And why the reason one RVR's may be debated -- clean plate, immune response, susectible sub-species, etc -- in any event it becomes a barometer of how well a particular drug is working.

But to jump to the monkey wrench side of the argument for a second -- until we have SVR data we won't know how protease Inhibitor (plus peg/riba) induced RVR correlates to peg/riba induced RVR, the latter which as been studied.

Also, and not talked about very much, is how durable traditional SVR will be using different drugs. Again, peg and riba in combination have shown that SVR (non-detect after six months post tx) is durable -- but it's possible that newer drugs added to the mix may change that equation. Still, on the whole, I'm personally very hopeful from everything I've read and heard, and should I theoretically need to treat again, I'd certainly look carefully at this newer approach. Based on the treatment I just finished, frankly I don't think I have another 54 weeks in me using current drugs. 12 weeks is SO much more doable. Remember Rifleman? 12 weeks in and out, now SVR. He's my treatment model.

-- Jim

[jmjm530]

Thanks for the nice words, well wishes and optimism.

Based on past history, I was expecting a little anxiety as the TMA test date approached, but not sure if that fully accounts for not being "my old self" yet.

Part may be some of the physical stuff DD has mentioned, part may be the "interferon hangover" my doc talks about, and part may be just the time our bodies and mind need to heal from such an ordeal which I have often likened to post traumatic stress syndrome in sessions with my shrink.

I also feel the minority of us who had to put their entire lives on hold during tx due to sides (unable to work, stuck to the couch/bed, etc) have a uniquely difficult time post treatment -- because not only are we dealing with coming off the drugs, but as we start to feel better, we have to start dealing with the re-intergration process of getting ourselves back into a society (work, friends, activities, responsibilities) that at some points during treatment were pushed out of the way due to necessity,  and therefore became a distant memory.

Time is a great healer, and and patience is our friend. Hopefully, you, I, and everyone will keep feeling better as the time moves on. And, yes, I am expecting a little (hopefully more than a little) kick when my post-tx three month viral load test comes in negative.

All the best.

-- Jim

[dyce]

This week sometime, had the draw done last wensday. Have to do another cbc draw tomarrow to see where the hmg is. I'm really feeling the anemia it seems . Having low blood really s-cks some life outta person.  

                         I've watched the anc and it willdrop to .7 or so and it'll jump back up to 1.5 . THen the next couple weeks it creeps back down to .7 then jumps back up again. It's seems the dyce'd body is tryin to keep up with the anc's but I look for it to go down far 1 of thease times.

                         There are a lot of illness's around here, my yougest daughter has bronchites and the resort I work at have people honking all over the place.

                         Thanks for askin, it's 3.00am and the dyce is rollin back to the rack!

[Forseegood]

in my humble little opinion on this, I agree with Willing and Jim on a lot of points made, but one thing I've believed from the beginning, to me it follows it's own logic...if it can get the viral load down, that fast, that is saying a lot...in my researching of this, just listening to people on these boards and elsewhere, which in not scientific by any means but it says something to *me* at least...is that people who went RVR within 4 weeks, seemed to have a much, much better chance at ultimately clearing the virus...whatever genotype...but of course, statistically speaking (and it's debatable how well they keep stats on this) the other genos have a better shot then geno 1s...

now if you can clear it really fast and you have much more of a "clean slate" to work with in terms of virus in the body...the other treatment drugs can clean up the mutators or whatever, so called "wild virus" etc...as simplistic as it sounds, perhaps the amount of virus you have in your body and cleaning it up fast has something to do with ultimately clearing it for good...if that makes any sense to anyone but me, ha ha!

[GoofyDad]

"... I could do 12 weeks of the stuff with VX-950 standing on my head; especially if I knew that I was being cured."


You mean I wasn't suposed to do the peg/riba tx standing on my head? I guess that explains my headaches, fatigue, difficulty sleeping, and trouble moving my bowels. But really, someone here could have said *something*. Sheeeeesh you guys!

[jmjm530]

Are you starting to feel the 12-week post tx VL test anxiety yet?  LOL. Another week or so and we're both due for a blood draw. Other than that how are you doing with sides, brain fog, cbc's, etc. I feel a whole lot better on treatment but certainly not my old self yet.

-- Jim

[jmjm530]

Milked says: "... I could do 12 weeks of the stuff with VX-950 standing on my head; especially if I knew that I was being cured."
---------------
Understand exactly what you're saying. I was hit hard and early by my sides, but my major concern early-on wasn't so much being able to handle the sides, but my fear of having to stop treatment early because of deterioration over time.  For most folks, 12 weeks is a very doable number compared to the 48 or more many of us do.

-- Jim

[dyce]

Jim , I hope this is the real deal! I'm at 12 weeks and the brain fog is takin it's toll. At work I'm really having a harder time, laughin 1 minute , da-m near at tears the next. Like you and others here, I could run like a deer, now I can't hardly pull 2 flights of stairs .

   I hope svr for you  and all in here, it's day to day now with work. One bonus , the house keepers said if I go down , cpr would be administered .LOL

[can-do-man]

As for standing on your head. Since you spend so much time on the Commode. I think your fine, standing or setting should not make a difference.

[GoofyDad]

No. No anxiety yet. I do have my momments of doubt. I've been tired this week, like I'm fighting a little bug, and of course right away I leap to a conclusion on what that 'bug' might be!

Well actually, I just pulled up my calendar and I see a note for the first week of June. That *is* soon. Now the seed of anxiety has been planted. Arrrgggg.

[jezzbe]

Was told trial is blind  with a placebo so a 25% chance of not getting the vx950, also will not get blood test results in real time. Is it still worth doing,I am trying to decide ,any advice or comments appreciated.

[susan400]

I wonder when they say Peg with Riba and VX, etc., etc. if it has to be Pegasys if one could go with Peg-Intron.  I responded better myself to Peg-Intron than Pegasys.  Pegasys was a bust, a big waste of time, for me.  And in fact, my viral load went up and my LFT's went up.  Just curious on that.

Susan

[Alady1620]

If you need to treat and you have this option, I think you should do it.  At least there are no placebos so you know you're going to get some kind of treatment.  This stuff is really promising.

I think they're stopping the vx950 at 12 weeks bc all it does is stop the virus from replicating.  If you clear at 12 weeks, it makes sense that you wouldn't need the PI anymore.

[jmjm530]

On line now at http://www.vpharm.com/  with some Q & A's. Wasn't looking at my clock, but took about 30 - 60 minutes to listen to. Webcast in some, but not all of the gaps.

Some random thoughts from the webcast to best of my note taking ability:

1. Phase 2 preliminary SVR data (3 months post) on 12-week arm of Prove I trial, to be available in early 2007, with 6-month post tx data (SVR) to follow 3 months after. Then a "torrent of data" (their words) will start flowing in from the rest of Prove I and Prove II all throughout 2007.

2. While they hedged in Q&A -- seemed like they're aiming for a > 75% SVR rate which (in their words) would be "transformational" therapy for genotype 1's.

3. They also hedged a bit on the differences between the American (Prove I) and European (Prove II) studies, saying it had to do somewhat with the European approach and leadership in shorter treatments, but another moderator later stated that the respective studies were designed in consultation with the different regulatory bodies. I read this to mean the American approach is more consertative due to FDA considerations.

4.  Expanded phase 3 trials are  projected to start mid 20007.

5. Depending on how stage 2 goes, they may drop the Vertex Placebo arm for phase 3. This should be good news for Jezzbe and others interested in the trial who may not want to end up in a placebo arm, should things get that far.  

6. In spite of the various treatment times, Vertex is still confident that they will end up with a 12-week therapy either in combination with peg and riba and perhaps just in combo with peg.
No mention was made at this time about Vertex only dosing.

7. I wished some of us could have asked a few questions. The ones asked for the most part were not all that interesting although the answers were somewhat enlightening to the process of how a drug gets to market by balancing both business and scientific concerns. And I guess in the real world that's how it works with all the drugs.

8. Lastly, and very important, for those new to the topic -- there has been no SVR (cure rate) data to date. While I think we all have reason to be optimisitic, so far all we know is that Vertex dramatically reduced viral load in a small group of patients in a short time. Again, preliminary SVR data will not be in until early 2007. No guarantees.

[jmjm530]

As Milked stated, all phase II trials will only use Vertex for 12 weeks with various add-ons. My initial post summary in "B" which was limited to Prove I, should therefore have read: 12 weeks with Vertex in combo with Peg and riba followed by 12 weeks of just Peg and riba (24 week total).

Here are all the different groups being tested per the press release for both Prove I and Prove II. The "A" at the end of each group is for Prove 1 which is being done in the United States. "E " is for Prove 2 which will be done in Europe

1)  12-week regimen of VX-950 in combination with peg and ribavirin (A &E)

(or)

2) 12-week regimens of VX-950 in combination with only Peg (E)

(or)

3) 12-week regimens of VX-950 in combination with peg and ribavirin, followed by 12 weeks of peg and ribavirin. (A&E)

(or)

4)12-week regimens of VX-950 in combination with peg and ribavirin followed by 36 weeks of therapy with peg and ribavirin.(A)

4)  A control arm with peg-IFN and RBV dosed for 48 weeks. (A&E)
----------

It appears that the more conservative approach (no riba in #2 and an extended course in #4) has been taken in America, and the more agressive approach in Europe. I suspect this has something to do with FDA approval.

[jmjm530]

Jezz,

As stated above, the placebo arm for Vertex may be dropped in Phase III testing projected for mid 2007, depending how phase II goes. As sometimes happens with trials, they don't give out blood results in real time, which may be the case here.

Waiting for the trial is a complicated decision because we still don't know how effective Vertex may be. Lots of considerations including your age, amount of liver damage, etc. In other words, how you perceive the risks/rewards of treating now verus waiting for a still unproven treatment. Depending on all these individual variables, options may be to (1) treat now conventionally; (2) treat now in an available trial; (3) treat mid 2007 in a projected Vertex Phase III trial; (4) Wait maybe a couple of years beyond, when Vertex hopefully will be available to everyone where you will be able to get real-time blood tests and  more individualized non-trial treatment. Of course, the big X factor is whether the drug will produce SVR's in a better a safer way than conventional treatment.  

Goof, Sorry I brought up the 12 week post tx VL test. You were so on the 4 week test, that I just figured the 12 week had to be on your mind as well. Anyway, in another few weeks it will all be academic as we both can drink (whatever) to our 3-month negatives.

-- Jim

[Forseegood]

you've got plenty of other seeds in your body besides the anxiety seeds, try focusing on those for awhile, for a change, ha ha!

[Forseegood]

that might of sounded insensitive, you know what I mean, just don't want you to worry, youre clear kid...know it in my bones...