Vertex/Boceprevir -- Rumor Mill

[jmjm530]

"...Shares of Vertex Pharmaceuticals Inc. rose Monday as a Cowen and Co. analyst said upcoming data on Schering-Plough Corp.'s boceprevir oral Hepatitis C drug isn't likely to show a cleaner profile than Vertex's telapravir, nor better sustained viral response..."

http://tinyurl.com/create.php

[copyman]

I know what you mean about waiting, it is the worse! What kind of liver damage you have? Why not re-treat but add alinia to SOC. If I was a stage 2 or more i would not wait and would treat again with alinia added. If your doctor will not let you tx again then find an aggressive doc that will. Best of luck

[geterdone]

Lol, not that good at understanding but just enough to make a quilt to cover thy butt if the unthinkable should happen down the road. Bummer on two fronts, Snow and taxes, I’ll take the snow if I had my druthers, lol.

jasper

[Proactive]

glad the link was of help to you, you're a better man than I if you can understand it!! (lol)...and what the heck, I'll put my neck on the chopping block...........IMO, these shorter trail arms may be a result of the PI drugs effectiveness plateauing rather quickly (there are a few charts out there that show this plateau/rebound after a few weeks)...just my opinion-fire away(g)..Spring is still a few months away here, in fact another 8" of snow is possible for Friday. Off to see my tax guy this morning....bummer!..;^)

[geterdone]

Thanks for the link, it has information I was looking for pertaining to Telaprevir and its 8 week dosing strategy in the up coming phase 3 study.

Hey! Spring is just around the cornerand no more shoveling or spreading salt.Wooo Hooo!

jasper

[Proactive]

Just so everyone is on the same page, this was HR's opinion (speaking of which, I think we are very fortunate that he shares his opinions with us, he's an out of the box thinker, placing himself out on the limb,IMO in that territory one should expect 2 steps back, and hopefully a major step forward)

"To: George
If you are looking carefully at the Alinia presentation by Dr. Korba at the hepdart conference that proactive has provided somewhere below, you will see the important factoid, that testing the in vitro efficacy of NTZ against geno 1a and 1b showed a high inhibitory efficacy, thus we have now direct data to support at least reasonable expectations for similar efficiencies against genotype 1a and b in vivo. With all the usual reservations, this seems to be a bit of real good news.

Overall one must not expect wonders from NTZ, but a robust helper role. If someone was a nonresponder with SOC, then the addition of NTZ in a new attempt is rather unlikely to push the deeply rooted inability of SOC to reduce the virus enough towards elimination to achieve SVR. It is important to have realistic expectations. *******Similarly, IMO, in such a particular case, the addition of the currently tested Polymerase inhibitorsAlpha-glucosidase inhibitors to SOC are not too promising to tilt the scale towards SVR."
.................................................................
Not to put words in his mouth (hopefully we can get hime to comment further when he returns), but I'm guessing his opinion is somewhat based on PI monotherapy trials and hcv resistant variants to the PI's (hence that added SOC drugs)....If you want to boggle your mind here is a link that goes heavy into these resistant variants, comparing various PI's effects on those variants
http://www.jbc.org/cgi/content/full/282/31/22619

[scratchinghead]

This thread was harder to read than my medical bills.

[willows]

now, if you can get my lettuce to sprout and the FDA to approve telaprevir, my life would be good good good!  

It's very hard to wait, but when I think really hard about it...waiting is wayy easier than it will be to take up the bottle and syringe again, choking down the riba.....wowsers, way easier.  All things in time, right?

You are always a voice for the right facts and  good information, do we tell you thanks enough?  Me, I'm too cranky to be much good at posting.  I keep hoping the alleviation of crankiness by at least 2 log will come to me with SVR.....someday..........as noble as any hope, I think!  Take care of yourself.

[jmjm530]

In short,, it seems to me at least, that adding a PI to Peg and Riba would be your best next step.

[jmjm530]

Willows:
But jmjm, if your take is that telaprevir won't work on anyone who never reached UND...
------------------
NO, not my take. It was HR's take and Dr. Sh's take, as related by Susie007. Specifically they seemed to imply that prev SOC  non-resonders (less than two log drop at week 12) won't respond to triple therapy. My point was that I haven't seen anything published on this therefore I question THEIR take.. But in any event, you were a responder but had what appeared to be a viral breakthrough of sorts. So, even if their take is correct, it doesn't appear to apply to you.

-- Jim

[willows]

you both have characterized the one question I cannot seem to get an answer to....I DID have a 2 log drop at 12 weeks, from 3 million to 100,000, but at 30 weeks I spiked back to 800,000 and in 2002 (time of my tx) conventional wisdom was to stop tx.  So my doc did.  So I responded...virus went away...and then I responded again...virus came back.  So where will someone with my profile fit into the PI regime?  I believe since there has not been the extensive testing done on folks like me YET, that it will be awhile before anyone knows.  

But jmjm, if your take is that telaprevir won't work on anyone who never reached UND....well, that just puts a big knot in my bonnet.   Since protocols still allow me...if a doc would agree...to try SOC again....to me it makes as much sense to go ahead and add the PI.  I have to believe if telaprevir is approved for non-responders...however broad the definition may be...I will give it a try and not stress about creating another resistant variant, because the simple fact is..for me... at age 56, having progressed one stage in 6 years, the numbers call for trying to retreat and don't look good any other way.  I can wait until the first PI is approved, 2010 or so...but then I'm cruisin towards developing the WORST profile available...age 60, stage three non responder.   Really knots my bonnet.

Perhaps I have misunderstood the definition of non-responder....it sure would be great if someone could help us with it.  Perhaps Susan or HR can chime in.

Willows

[jmjm530]

gluk: the statement i heard was that if you had not  2 log drop in SOC, the odds were not good at all that you would clear and stay clear with VX.
--------------------------------------------------
Did you have a different source for that statement, or was it one of the two sources I mentioned -- HR  and/or Susie's characterization of Dr. Sh's take on things?  
I haven't seen anything about this in writing or heard it from anyone else and it's been awhile since the conference from when these opinions seemed to emanate.

-- Jim

[glucklich]

the statement i heard was that if you had not  2 log drop in SOC, the odds were not good at all that you would clear and stay clear with VX. That was followed by the comment  that the reason for this was not yet understood, and that perhaps removing the blocker for SOC would enable VX.

[jmjm530]

To be accurate, not sure if HR and Susie made the statement "not respond" in an absolute sense, but it seem strongly implicated at least in HR's posts as I remember them.

[jmjm530]

Willows: The docs give me 10% if I try SOC again and the current percentage is about 60% for PI's and SOC.  So if I try and fail.......a definite possibility.....and I am left with another resistant strain, am I any worse off?
------------
That was more or less my doc's take when I discussed resistant strains. He alluded to other drugs down the pike if one didn't work.

That said, I believe both HR and Susie (recollecting a conversation with Dr. Sh) suggested that if you were a non-responder with SOC, then you will not respond with a PI like Telaprevir -- not respond, not 60% chance. As far as I know, nothing has been published on this so those assertions seem dubious. In any event, I imagine the issue will be put to rest once data comes in from the treatment experienced trials. Something to keep you eye on.

-- Jim

[willows]

I guess it is all a matter of odds....right now I have no chance of clearing, as I am not tx'ing.  The docs give me 10% if I try SOC again and the current percentage is about 60% for PI's and SOC.  So if I try and fail.......a definite possibility.....and I am left with another resistant strain, am I any worse off?  If the current strain I carry is destroying my liver, will a resistant strain do it quicker?  I'm dancing around here, because I believe the true "cure" won't really come in my lifetime.  It took about 30 years to get the HIV cocktail truly down to a science, from what I can gather......

None of this rocks my world.  We've all spoke at length about the personal nature of the choice to retreat or not and I'm just publically talking to myself about my own decision.  Who knows?   Take care

Willows

[Proactive]

I tend to agree with Jim's interpretation of McGinn's statement of "cleaner profile", but honestly don't know what that staement is based on, and won't bother to guess..I'll also going to avoid any comparisons due to a lack of no new info, at least that I have access to.
I will make a general comment about all these PI drugs, I do believe the side effect profile (to include wild type/mutated strains of HCV as a result of treatment with the new PI's) will be one of the biggest hurdles to overcome for the FDA in the end game approval process..
(this is touched on just a bit in the Alinia slide set(7th slide) I posted earlier by a thrid party--not that I'm smart enough to understand it (G))
http://www.informedhorizons.com/hepdart2007/pdf/hepdart07_presentations/Tues_04_Korba.pdf

willows, IMO, if you can wait until at least the new round of ph2 trial data comes out, this may be a smart approach, better yet, wait for the first round of ph3 data...my biggest reserve on all these new drugs is, what if you don't clear(sorry,a reality)--has a new resistant strain been created as a result of using the PI's?

well.. off to shoveling, got another foot of snow here last night, can barely see out my windows anymore (g)

[willows]

Well, the only reason I'm not in a trial is that they wouldn't take me.  My doc and I tried, but here in the Pacific Northwest, Vertex was taking only 2 non-responders and my viral breakthru made me the most unattractive choice of all.  So I keep trying.

Time line wise, there is not way Telaprevir can NOT be first..even with the uneven decision making coming out of the FDA these days.  Vertex may only have an 18 month head start on the rest of the pack, but numbers is numbers, Vertex is waay ahead in the required trials.  

From the last conference call I understand Vertex might ask for a portion of phase iii to be accepted as the registration trial for telaprevir for non-responders?   We fit the bill, a bad disease..and no other tx out there that works.  Maybe we will get lucky by about 2010.  I keep hoping.  

I am always surprised by folks here who talk about retreating soon after rebound, etc.,,,,I cannot find a doctor that will give me any better odds than about 10% and the only way I'm going to get SOC again is to "get medieval" on someone.  I CAN do that, but am listening to my docs advice for now.  It's just the 2010 seems so far away.  

The stock price?  It's gonna go up and down and up and down.  Biotech is all about the FDA approval, from what I read...so it's a wide open game for about two more years.  Rough game for a girl.

Willows

[willows]

Well, the only reason I'm not in a trial is that they wouldn't take me.  My doc and I tried, but here in the Pacific Northwest, Vertex was taking only 2 non-responders and my viral breakthru made me the most unattractive choice of all.  So I keep trying.

Time line wise, there is not way Telaprevir can NOT be first..even with the uneven decision making coming out of the FDA these days.  Vertex may only have an 18 month head start on the rest of the pack, but numbers is numbers, Vertex is waay ahead in the required trials.  

From the last conference call I understand Vertex might ask for a portion of phase iii to be accepted as the registration trial for telaprevir for non-responders?   We fit the bill, a bad disease..and no other tx out there that works.  Maybe we will get lucky by about 2010.  I keep hoping.  

I am always surprised by folks here who talk about retreating soon after rebound, etc.,,,,I cannot find a doctor that will give me any better odds than about 10% and the only way I'm going to get SOC again is to "get medieval" on someone.  I CAN do that, but am listening to my docs advice for now.  It's just the 2010 seems so far away.  

The stock price?  It's gonna go up and down and up and down.  Biotech is all about the FDA approval, from what I read...so it's a wide open game for about two more years.  Rough game for a girl.

Willows

[willows]

Well, the only reason I'm not in a trial is that they wouldn't take me.  My doc and I tried, but here in the Pacific Northwest, Vertex was taking only 2 non-responders and my viral breakthru made me the most unattractive choice of all.  So I keep trying.

Time line wise, there is not way Telaprevir can NOT be first..even with the uneven decision making coming out of the FDA these days.  Vertex may only have an 18 month head start on the rest of the pack, but numbers is numbers, Vertex is waay ahead in the required trials.  

From the last conference call I understand Vertex might ask for a portion of phase iii to be accepted as the registration trial for telaprevir for non-responders?   We fit the bill, a bad disease..and no other tx out there that works.  Maybe we will get lucky by about 2010.  I keep hoping.  

I am always surprised by folks here who talk about retreating soon after rebound, etc.,,,,I cannot find a doctor that will give me any better odds than about 10% and the only way I'm going to get SOC again is to "get medieval" on someone.  I CAN do that, but am listening to my docs advice for now.  It's just the 2010 seems so far away.  

The stock price?  It's gonna go up and down and up and down.  Biotech is all about the FDA approval, from what I read...so it's a wide open game for about two more years.  Rough game for a girl.

Willows

[jmjm530]

I think what they mean by "cleaner profile" is side effects, i.e. the analyst doesn't expect Bocelivir to have a better side effect profile than Telaprevir.

I assume you have good reasons for not doing one of the Telaprevir trials, but I guess the silver lining for waiting is that more information will be available by 2010, and perhaps even better drugs. BTW very recently my doc said some good things about Telaprevir and seemed more bullish on it than let's say a year ago. Basically he said the results were good and coming from him -- and I believing he's also trialing competing drugs -- that's a very good endorsement.

As to viral resistance issues for prior non-responders, hopefully these  questions should be answered with the ongoing trials.

As to the stock, I suppose the main thing driving the price now is not whether Telaprevir is a good drug, but whether it will emerge as a lead dog drug from the current crop. That's why bad news for Bocelivir is good news for Vertex investors.

-- Jim

[jmjm530]

I think what they mean by "cleaner profile" is side effects, i.e. the analyst doesn't expect Bocelivir to have a better side effect profile than Telaprevir.

I assume you have good reasons for not doing one of the Telaprevir trials, but I guess the silver lining for waiting is that more information will be available by 2010, and perhaps even better drugs. BTW very recently my doc said some good things about Telaprevir and seemed more bullish on it than let's say a year ago. Basically he said the results were good and coming from him -- and I believing he's also trialing competing drugs -- that's a very good endorsement.

As to viral resistance issues for prior non-responders, hopefully these  questions should be answered with the ongoing trials.

As to the stock, I suppose the main thing driving the price now is not whether Telaprevir is a good drug, but whether it will emerge as a lead dog drug from the current crop. That's why bad news for Bocelivir is good news for Vertex investors.

-- Jim

[willows]

I read this article this a.m. and the part of it that keeps rolling around in my head is..."cleaner profile"....what does anyone suppose that means?  And why don't these people speak English?  

Perhaps they speak so convoluted as to make it more difficult to call them on a mistake...or they do NOT actually want to be understood.   Vertex stock has always been bounced around by every whim and bit of analyst pondering....my impatience must be showing.   2010 is such a long time to wait for telaprevir, but that is what my doc wants me to do.  I have this very smart gut and it tells me that telaprevir WILL be approved, it's just so hard waiting.  My liver doesn't like it much either.

Do I need to be on the lookout for the escaped varient?  I'm pretty good with a broom when it comes to shoosing away the possum in the cat food, bet I could get after that varient.  I'll let you know.

Willow

[Bill1954]

Thanks Jim- I'll slide my Geritol down the bar to you after I take a swig myself :o).

Pro- thanks also. I really haven't been following much outside of SOC for a number of reasons. I don't participate in market investment, so that influences my interest level as well.

I do know a fellow with our local support group that was involved with the early Boceprevir trials (SCH 50304?). This was about two years ago, I have no idea which arm he was in; but his viral response was all over the map- i.e. 100k, 19k, 1.5 m, 240k, etc. The particular arm he was participating in was apparently shut down by the FDA due to some kind of escape varient issues? I don't have any firm info, I can find out in two weeks if anyone is interested.

Thanks again--

Bill

[Proactive]

I probably shouldn't have posted the ap release....but, you can't get blood from a stone-and who would want my blood anyways (VBG)
Looks like this McGinn likes to make assumptions...although I might agree Schering will do a late minute abstract release...they know how to play the game correctly..something about keeping powder dry....;^) Pro
(just my opinion-no links)