Vertex down 15%

Oh my

Just noticed that Vertex stock is down over 5 bucks a share. Over 15%.  I wonder who knows what. I don't own the stock but I hope its not a bad omen for the meeting.

                                                                                                                                        Ron

[mremeet]

Yep, it's slippin' hard. I think the recent good news about SCH503034 is driving it down this time. Could be major competition for VX950, especially if SCH503034 doesn't have the rash problem that Telaprevir does. Plus, SCH503034 is at the same level of development as telaprevir is (phase IIb), so it could be FDA approved no later than Telaprevir...maybe even sooner. And this doesn;t even factor in Alinia and what it might bring to the table. Could be pretty dicey for VRTX stock for some time I think.

[Willy50]

As I type this Vertex was down about 20% to about $29.  It seems to be in the wake of positive data on boceprevir, the New compound being developed by Sherring Plough.  It looks as if the SGP compound will be comparable, but they only released a little data.  

IF boceprevir had better response rates then Vertex might not be the "lead" compound.  That means many investors could jump ship.

Per one of our posters here that was on the trial they reported that the SGP trials allowed "rescue drugs" whereas the Vertex trial did not.  This could be a situation where apples are being compared to oranges since the 2 trials are not set up the same.

Either way...... if you are a Vertex investor you might be crying.  If you are only an HCV infected person you might see this as having 2 potentially successful componds in development; a win-win.

When I first saw the stock drop like that I naturally assumed that it meant there was something amiss about Telaprevir.  I'm not so sure about that now; I think it's just the stock market going nuts over early news.  

Willy

[mremeet]

"Per one of our posters here that was on the trial they reported that the SGP trials allowed "rescue drugs" whereas the Vertex trial did not."

Not exactly. In the Vertex Prove 1 and 2 trials rescue drugs were prohibited only during the first 12 weeks when the research drug was in play. After that rescue drugs were permitted. In prove 3 Teleprevir dosage exceeded 12 weeks in some arms, so I'm not sure if rescue drugs were still prohibited after that time...but I think they still were (someone correct me if I'm wrong). There were also at least some cirrhotics in prove 3, not sure if any cirrhotitcs were allowed into the SCH503034 trial. Inclusion of cirrhotics will probably lower the overall SVR rate somewhat, so that might be another apples to oranges comparison. Either way, for the patient this is win win. For the investor, it's going to be rough going trying ot predict ahead of time who's gonna come out on top.

[Proactive]

"A total of 595 patients have been treated in the HCV SPRINT-1 study at sites across the United States, Canada and Europe, including 491 patients treated with boceprevir. Overall, 77 percent of patients in the study were enrolled in the United States. African-Americans represent 16 percent of the patients enrolled in the study and 7 percent of patients in the study are cirrhotic"

[jmjm530]

Pro: African-Americans represent 16 percent of the patients enrolled in the study and 7 percent of patients in the study are cirrhotic"
-----------------------
That could def account for the low SVR rates in the SOC group. It also makes the Boceprevir numbers look even better.

I agree, this is a win-win for us -- as to the investors, biotechs have always been chancy.

-- Jim

[Willy50]

here's a link to that thread;
http://www.medhelp.org/posts/show/324456

Mre, thanks.  I went back to this thread and saw it was a larger study and that appeared to have good..... in in some regards perhaps better results although really we've not seen much real data.

I think the point I was trying to make was that on the Vertex trials certain rescue drugs were prohibited during the VX treatment phase, not during the entire trial.  I got the impression that the Sherring trial allowed them during the trial compound treatment but it wasn't totally clear from the posts.  

IF the Sherring compound has comparable efficacy and fewer sides it could provide some real competition for Vertex.  About 2 weeks to go to AASLD.

here's a hot off the presses article by Adam Feuerstein on the subject;

http://www.thestreet.com/_yahoo/newsanalysis/biotech/10385195.html?
cm_ven=YAHOO&cm_cat=FREE&cm_ite=NA

Willy

[mremeet]

Yeah, not sure what's up with the procrit/anemia thing with the Boceprevir. According to a recent "quote of a quote" from Ironduke "I'm in the Scherring-Plough trial.  They weren't going to allow rescue drugs but so many people headed toward anemia that they changed the protocol and they sprung for Procrit." Not sure if this means anemia is a bigger problem with Boceprevir than it is with Telaprevir (which to my knowledge and experience is pretty minimal).

Also, isn't it odd that such a large cohort of over 800 Boceprevir test subjects are out there somewhere, and yet the only two I've seen since I've been on this forum (for over a year now) are "Ironduke" and "JOHNWS"? And those two just magically popped in here simultaneously just yesterday right on the eve of this test result press announcement? I dunno, I guess I'm getting paranoid in my old age, but what's that all about?? ;-)

[glucklich]

In this study of well-documented null nonresponders, some patients achieved a sustained virologic response (SVR). Overall, 7-14 percent of patients in the boceprevir crossover arms achieved SVR compared to 2 percent in the control arm.

Intersting

[Willy50]

working backwards;

Glucklich; "This study was complex, involving seven different treatment arms. Patients were initially randomized to low doses of boceprevir (100, 200, 400 mg TID) before initiating an 800 mg TID boceprevir arm."

I guess that this was their way of working into the drug but it may not provide the strongest antiiral response.  The jury isout on this one but they may be able to up the SVR rate.  When I saw that I assumed that the Vertex rate could be comparable.  I'm hoping for far more robust response rates in the Vertex trial.  This data scared me a little if you could extrapolate it into likely Vertex Prove 3 results.

MREmeet; Did you see the discontinuation results in this trial?
"Treatment discontinuations due to adverse events were 12, 9, and 8 percent for patients in the boceprevir regimens, respectively, compared to 5 percent for the control arm."

This treatment still may correspond roughly with the Vertex discontinuation results.  Frankly some of the information out there doesn't quite line up.  We have to actually wait till the data is out there and try to make actual comparisons.  Due to the trial designs I'm really not sure that we can accurately.

We may also be faced with a situation where ....lets say for argument if Vertex were more potent but had worse sides..... which way would people go?  We seem to be getting hype that the SGP drug has no sides and yet the discointinuations seem comparable to Vertex and yet some or even many of the folks were on rescue drugs.  

Willy

[JOHNWS]

I think they allowed rescue drugs. I beleive it was a trial coordinator decision. However with me they reduced the riba dose to control the anemia, the hep doc was not a big believer in procrit. I have been reading post lately, I jumped in recently because I received my last batch of drugs. I will continue to post and give updates for my post treatment blood results

[willows]

I second your paranoia and raise you a question...where have these folks been?

Willow

[Proactive]

seems you only show up when vrtx stock is discussed so I'll ask you..In light of todays stock price drop, which obviously is their currency, how much more profit/rights to sales of vx950 do you expect them to have to give away before marketability of the drug? When reviewing their cash burn rate, cash on hand & equivlents it certainly looks like the will have to dip into the well again to go the distance...What do you expect to be leftover for current shareholders?
Let's remeber what they already have given away..
"Under the agreement, Janssen will have exclusive rights in Europe, South America, the Middle East, Africa and Australia, and Vertex will retain exclusive commercial rights to VX-950 in North America."

[Proactive]

PS: I'll appologize now (for everyone) for posting my above question, because I do know we are on the wrong board!
....;^)

[jmjm530]

Mike may disagree with me, but I think you're on the right board. At least previous VX stock talk has been here.

The reason I think it's the right side is because any discussion of Telaprevir's price invariably turns into a discussion of Telaprevir, which belongs on this side. Anyway, as you know, there is a fuzzy line between the two sides and there can be honest disagreement over what goes where. Thanks for the update, it made for an interesting discussion and probably introduced Boceprevir to a lot of folks.

-- Jim

[glucklich]

Frankly I never get the stock enthusiasm. Given that the duration of treatment is so long and the demographics of the HCV population world wide is not conducive to a treatment with severe side effects, I think the market potential is tagged a bit high.

[willows]

Well, as a non responder, stage 3, waiting for telaprevir, yes, I guess the only time I get vocal is when Vertex stock is talked about.  Beats whining about how bad I feel, so many people here working hard on making it thru tx, my story does not add much.  

As for giving away rights...I think the people in charge of Vertex will give away whatever it takes to bring telaprevir to market.  They receive milestone payments from J&J for goals met on the trials, but I haven't seen one of those mentioned for a while.   With the CDC figuring there are about 4 million folks infected with HCV in the US right now and another 1 million in Canada, I believe Vertex will do just fine.  

I have the greatest doctor from the University of Washington hospital, he is so very enthusiastic about telaprevir....I just gotta believe him and hang until it is my turn.   As for the stock in Vertex, my gosh, talk about a wing and a prayer.  The whole market is in a very turbulent time, and biotech has always been so risky...ask any investor in Idenix.  So all I can do is walk the line and keep up with the latest news, because it means so very much to me personally.

[Proactive]

fair enough willows, and of course wish you the very best as a non responder..
"With the CDC figuring there are about 4 million folks infected with HCV in the US right now and another 1 million in Canada" Do you have any idea how many people are currently treating with SOC? At one time I found a number (I'll look again), but that number was tiny....are you expecting a flood of new treaters as a result of new PI's?

[Proactive]

Jim since we are straying a bit, I recall you mentioning you have been prescribed various ribas. Did you feel any difference with the various pills? I just started in with capsules, after 2 different tablets and thought maybe I felt a bit different, but figured it was just in my head because I did my morning shot today....Pro

[willows]

Well, conventional wisdom says that many younger folks are avoiding tx right now because of the horrific stories they have heard about IFN and riba.  If the odds are upped to 80% and tx time shortened to 24 weeks, seems to me that many more folks will do treatment.  I know I will try it again, in a heartbeat.  Has to be a piece of cake compared to 30 weeks of SOC, only to have viral breathru and have to quit.  In retrospect, that 30 weeks may have been a worse experience than I realized, my doc is concerned for any non-responder like me with viral breakthru, my virus mutated against IFN and does that mean that I will have a harder time than a naive patient?  Probably, but I think non-responders like me will become very much more rare in time, with the addition of PI's to tx.

After the $6.00 drop this morning, I have done some research on Scherings SCH503430.  It is worth the time to drop the name in google and go back to 2005 and read comparisions to Schering and telaprevir.  Telaprevir has been performing better for two years now, even with the re working of Scherings trials.  As I said before, space/time flows the same for any company and Vertex is so far ahead of Schering...I'm thinking it will be the first PI for about two years and then we will be flooded with so many new drugs.  All this is comparable to the history and evolution of the HIV/Aids arc.  Those sufferers now have 200 drugs to choose from...less of them are dying than from Hep C.  So I think there's room for telaprevir and Schering.  And I hope a lot more.

[Proactive]

I do agree. The price alone makes treatment of any type extremely exclusive.

[mremeet]

Forgive me for being a bit suspicious, but I'm just curious why you guys have come out of the woodwork only now? The very day of the first real news release, and both of you making your appearance more or less simultaneously (although ironduke made a post about a month ago). Do you guys know each other? Just seems a bit odd that we haven't seen any boceprevir subjects here, at least I haven't. Not a one in over a year of hanging here, and then you two guys come along exactly at the same time and on the exact date of the first real press release concerning the first test results. Plus both of you have happy stories concerning your viral performance in conjunction with minimal sides. If I were the suspicious and paranoid sort, I might think you guys are here to "manage" the interpretation of this newly released information. Please, tell me I'm a complete paranoid and allay concerns that you two might not what you appear to be. ;-)

[Proactive]

"Well, conventional wisdom says that many younger folks are avoiding tx right now because of the horrific stories they have heard about IFN and riba"..I think that is stretching it a bit. The sandman is knocking at my door and the evening fog is rolling in...'nite Pro

[Cheesegrater]

I took a look at the text at
http://www.natap.org/2006/EASL/EASL_15.htm

I'll cut and paste here...

Sequence Analysis of HCV Protease
-- 18/19 patients had no detectable variants
-- patient #105: a single mutation at position T54 was identified during SCH 503034 mono- and combination tx
-- Variant became non-detectable after washout period
-- Quasi-species analysis are under way
NOTE from Jules Levin: at the meeting after Zeuzem gave his talk I asked him from the microphone why they had so little resistance, 1 mutation in 1 patient, compared to VX-950, for which Vertex presented much resistance data, the response Zeuzem said was-the resistance test used in this study was not as sensitive and SCH503034 was not potent enough to cause resistance.

I guess we might hear more about mutations and resistance as the trial continues, or when all the data is in.
The current schering data is from an ongoing trial, is it not?

Cheese

[merryBe]

can't find trial 3 anywhere, and now this....from my days trading stock I'd say those in the know have already blown town. That and how is the competion doing, market wise?

[JOHNWS]

I am not on here as some type of plant. I was told not to post, which I have not been doing. I was just happen with my results so far and thought it would be nice to share with the community here. The reason I just posted was I received my last 4 week supply. The road has been tough, constant anemia and on and off GI issues, no rescue drugs for me. I do not know which trial is better, I believe based on everything I hear no difference between the two drugs except more rash with Vertex and more anemia with SCH. I do know that SCH increased the dosing of its drug to 800 mg 3 times a day, that is higher than previous trials. I believe that is why Vertex may have done better in the past. In addition Vertex started with treatment naive whereas SCH started with non responders. We are all in this together. Just trying to share information as much as possible. Maybe I would have responded without the SCH drug I do not know as I was treatment naive.

[jmjm530]

I think I share the sentiments of most here that your posts are not only welcome, but very important to share with our community. Please do not let the suspicions of one member get in the way of that. This place is pretty much unmoderated and sometimes can get a bit like the old West. That said, lots of good infomation here and hopefully you can become a part of that information stream, just like the Vertex posters (like MreMeet) have been a part of that stream with the Vertex trials.

All the best with your treatment,

-- Jim

[jmjm530]

Just want to add that hopefully this does not come off as a criticism of "MreMeet" who is a valued member here and has helped enormously dispensing Telaprevir trail data.He is entitled to his opinions/suspicions, but personally I think he sometimes sees things where they aren't, and this has happened in the past with one of the Vertex posters. Well, that's my opinion.

[JOHNWS]

additionally, I pray that the two have the same results. As I am in the 28 week arm, I worry that it may not be long enough. I have been undetectable the whole way on this compound. I do not want to post after stopping treatment that I have relapsed. Going through this once is enough. I take my hat off to all of those out there that have had multiple treatments, you guys are stronger than me. I have wanted to quit many times however I try to take it one day at a time.

[jmjm530]

Is it possible to share more about your stats and the trial. Such as your genotype, stage, age, race, pre-treatment viral load, specifics of the dosing, and any viral load test results and dates, etc. Your trial is new to a lot of us here. Thanks.

-- Jim

[JOHNWS]

Genotype 1a, starting viral load 6 million, stage FO with moderate inflamation (inflammation), age is 43, white male. The dosing is 4 200mg SCH503034 three times a day. I started this the same time with the Peg intron and Ribavirin. The Ribavirin dose was 1200mg, it has been reduced to 600 mg. The first dose redution was around week 4-5 the second dose reduction was around week 12, then the third was around week 20. Hemo levels have been in the 9's throughout thearpy.

[jmjm530]

Thanks for the info. Was the riba reduction per protocol or because of anemia and/or side effects? What is the policy with helper drugs such as Procrit (epo) and Neupogen?
Around what did you weigh when you started treating? I assume this is the first time you treated? Forgive any redundant questions you may have answered before.

-- Jim

[jmjm530]

Forget to ask when did they test for viral load, and what were your results.

[mikesimon]

The market is down across the board today. Mike

[mremeet]

Johnws thanks for the comments. I have no way of knowing if you're a "plant" or anything like that, that's why I just thought I'd pose the question in a direct manner to you both and see what you had to say. Both you and ironduke seem like nice people and if you really are in the trial, obviously we would like to hear from you. The only reason I asked for clarification is because of the odd timing of both of you showing up simultaneously and on the *exact* day of the press release. And not one out of over 800 boceprevir trial participants have ever stopped by here yet or have become regular members (not that I'm aware of anyway). A trial cohort that large is even larger than the number of Vertex Prove 1/2/3 trial participants, and yet we've had a lot of Telaprevir participants here for over a year now (including myself). So I just thought it was strange that's all. Of course this is the internet and you never know who you're talking to on an anonymous board like this. Plus day traders (and full fledged stock brokers) read this forum in order to get the latest info on how the trials are going from actual participants so they can garner some insight on where volatile pharm stocks are headed. Some of them have thousands or even millions of $$$ on the line. And yes, there's also the possibility one (or more) of those traders may register on this forum and pose as a trial participant - in an attempt to either make the stock go up or down, depending on how they're positioned. Lastly, in the case of the Telaprevir trials, Vertex became aware of our discussions concerning our trial experiences. They were very unhappy about it and communicated their displeasure through our doctors. Some participants were even indirectly threatened with discontinuance if they did not "cease and desist" posting their experiences on forums like this (mainly this one). This internet drug trial participant info sharing phenom is a pretty new thing, and it's been widely discussed at liver forums amongst trial doctors and Vertex reps alike. So I'm more than certain that Schering Plough knows all about internet discussion groups and would not like any discussion of test results coming from any trial participants (as reflected by your statement "I was told not to post"). The possibility that someone from SP might come onto this board posing as a trial participant (or two) in an attempt to control or otherwise manipulate the interpretation of the trial results is just that...a possibility. (albeit probably unlikely considering the questionable ethics and legalities of such an action)

But either way, you deserve the benefit of the doubt. Even if you were a fake, the truth will out itself one way or another, sooner or later. So thanks for joining us, it's great to FINALLY hear directly from boceprevir trial participants about their experiences. Best of luck on your remaining treatment.

[jmjm530]

Yikes. Days like this I'm glad on sitting on the sidelines.

[mremeet]

Jim, you really don't need to chase me around this forum constantly following up my posts with "corrective" remarks or "dilutive" remarks or by re-characterizing what I said or meant so that it can become clearer to the person I was addressing. That's not your job. And being the self appointed policeman around here is also not your job. And being the self appointed MEDHELP HEPATITIS SPOKESMAN WHO SPEAKS FOR ALL MEMBERS! is also not your job.

And as far as paranoia and seeing "things where they aren't" - how do you know who is who around here jim? Have you personally met and spoken to everyone on this forum? Can you really tell one way or the other conclusively that everyone here is who they say they are?? Jim, how can you know that with such utter certainty?? Please explain in only the way that you can jim, because I'd really like to know that. ;-)

[JOHNWS]

The riba reductions were because of the anemia, my hep doc does not believe in rescue drugs. My weight was 193, down to 184 now. Yes, I am treatment naive. There are GI issues that when they flare up drive you crazy for a day or two. I was thinking of stopping the riba the last couple of weeks, as I wonder if there is additionally benefit in continuing the riba at this stage, just sick of having low hemo levels. They tested for viral loads the day of the first shot. 6 million was intial load, they then tested at two weeks undetectable <30 was the result.

[mremeet]

"I was thinking of stopping the riba the last couple of weeks, as I wonder if there is additionally benefit in continuing the riba at this stage"

If I were you I wouldn't stop the riba. At this point in your treatment the riba is probably providing more value to you than the protease inhibitor. In the telaprevir trials those who were only dosed with IFN+telaprevir eventually experienced viral rebounds during treatment or relapses after stopping (in *every* case reported here). These PI's NEED to be dosed with interferon AND riba in order to work. If the anemia has got you down that bad, go see a hematologist (or another experienced hepatologist) and get some procrit if your anemia is that bad. Also maybe consider the possibility of halting the boceprevir, considering it's probably a significant contributor to the anemia (in addition to the riba) and in all likelihood has long since finished the "heavy lifting." Good luck.

[JOHNWS]

I found an interesting article not sure if it has been posted here yet
here it is
http://natap.org/2007/DDW/DDW_36.htm

If this is true then 28 weeks should be plenty

[Willy50]

John, I'm happy to see you here and posting.

If we people WANT folks from the Boceprevir trials posting we can try to make them feel more welcome.  Vertex has had large Phase 2 trials on for one and a half years; over 1000 have treated  (how many of them have we met here?).  Boceprevir is behind in the trials and only has had this large trials recently.  It seems logical to assume that we would meet fewer here.  Furthermore, since most trial participants are told to keep mum about many aspects of the trial it's also likely that many will do just that.  These folks who have only recently posted are perhaps only now getting information on their results.

If we want to welcome people....if we want to get some information on the trials (SGP hasn't been "schering" much until very recently  : )), I'd drop the skepticism and just replace it with a polite welcome.  

I'm glad you're here John (and any other Boceprevir trial participants).

best,
Willy  

[JOHNWS]

Thank you

[mremeet]

Yep, considering your fabulous early viral clearance, based on what we now know about telaprevir's ability to deliver SVR's with as little as 4 weeks of treatment, I'd guess it's more than likely you've been SVR for months now.

[jmjm530]

Mre: And as far as paranoia and seeing "things where they aren't"
------------------
Yes, indeed, I could have worded that a lot better, and have often wished for an "edit" function here. I do apologize because it came out wrong. Just trying to make John more comfortable, not you uncomfortable and your points about not knowing who people are here are well taken.

And as far as "following someone around"  or characterizing what people say -- frankly, I took offense when you did just that the other day when you said to me

"...Not trying to put you in the hot seat, but frankly I do think you sometimes intimate an overly blase "ohh it's not so serious" vibe when discussing a possible plan of action when it comes to people with advanced fibrosis (i.e F3)..."

That doesn't mean it's right for me to do the same or similar. In the future I will try and stick to tropics at hand, and not the person behind the topic, and I truly hope you do the same.


-- Jim

[mikesimon]

Jim meant that - in the future I will try and stick to "topics"  at hand and not "tropics" at hand. I personally would prefer the tropics but that's just me. Mike

[Willy50]

By the way......the data we have on Telaprevir suggests that what MREmeet is saying has some basis.  I'd say it's right on except that it hasn't been officially validated as of yet but that it may be reinforced further at the AASLD.  We are probably more likely to shoot from the hip about our takes on these things.  Scientists may not officially confirm such things for years.  I still feel that it's sound advice or a reasonable "take" on your status given the amount of information floating around

My assumption is that we may see a relationship between the current lead PI's (Telaprevir and Boceprevir) that may mimic the relationship between Peg-Intron and Pegasys; not identical but very similar.  Extending that relationship further we may even see them design trials so that the results are not easily compared.  If the differences are obvious that might be one thing but if they are closely similar in performance neither one may wish to be decisively proven to be inferior to the other.  Both know that there's plenty of business out there for them without having proof that they are #1 or #2.  For this reason we may actually not see clear comparisons.  (Has anyone wondered what the outcomes would have been in the Boceprevir trial with Pegasys?-that trial may be a ways off. : ))

If the two compounds are similar and you can compare the results of the Prove trials to the Boceprevir trials you may indeed be "out of the woods".  

On the other hand.....the early trials of Boceprevir showed less viral efficacy than Vertex's compound.  IF it were so..... you may need a longer triple therapy treat time or followup with SOC to better assure oneself of an SVR.  The data to support a conclusion really is barely out there yet for Vertex.  I'd be even more cautious about reaching one about Boceprevir treatments.  It might be better to be safe (in overtreating a little) than sorry.

best,
Willy

[Proactive]

How on earth can anyone make a comparison between Telaprevir and Boceprevir? One simply doesn't have the data, seems like a waste of time to even attempt it.

[susan400]

It doesn't really matter to me at all what happens with the stock with either one of these drugs, as I'm not invested in either of them.  What does matter to me is that there are new drugs being developed that may be a potential treatment for me down the road, that may actually work and that may actually not give me the huge rash that the VX did and that also (as a bonus), may allow rescue drugs.  I don't even care if they pay for the rescue drugs-as long as they will allow me to take them if I need them.   Susan

[nygirl7]

Amen sister a voice of reason!  As long as they are investigating other drugs in addition to Vx which just might not pan out - things are good.  It is NOT a one size fits all world - unfortunately there might be several options required for different folks.

[Willy50]

They are both  protease-inhibitors, they work on the same concept.
They are both in Phase 2 trials
The response rate is not only similar, but identical ( 79% RVR'ed in both trials; I'm using Prove 2)
We have members from both trials, I think comparison is natural.
John had a theoretical treatment question and MREmeet tried to respond while couching it in that it was  from general data.  By the time there is "fact" Johns treatment will have long ended.

I just tried to buffer the information.  We don't really know.  I agree that it's too soon to draw conclusions but perhaps not to make comparisons.  I pointed out yesterday in several posts that the trials were different and so we couldn't/shouldn't really compare them and I also did so somewhat in my last post.

best,
Willy

[nygirl7]

The more trials the merrier is my opinion.  Welcome to John and his new information right?  It's all neither here nor there as long as they are working on finding cures for heppers. The rest, all moot and FUN to discuss and compare!

[JOHNWS]

Great information and thanks to everyone that inputed. I agree with Susan who cares about stock price as long as these compounds work and cures all of us of this evil disease. I know it is hard to compare the two, the reason I was asking was obviously Vertex has released alot more information than SCH has. Does anyone know the difference between a serine protease inhibitor which is the SCH drug and the Vertex drug which is a different protease inhibitor. I asked the research nurse why peg intron and not pegasys she said SCH does not allow pegasys in its trial because it is made by a rival company.

[susan400]

That doesn't matter to me that they use Peg-Intron because I actually had a better response rate with  Peg-Intron than I ever did with the Pegasys-even though the sides were a little bit harder between the 2, given a choice, I'll take the rougher sides of Peg-Intron for the better response rate (in my body).  Granted, on paper and in other people's experience-the Pegasys might have more documents supporting Pegasys - I have no idea....I'm sure that there's some piece of paper somewhere saying the Pegasys works better---I haven't even bothered to look into it, I just know that in my body Peg-Intron had a better viral load response than the Pegasys.    Susan

[abby105]

there are lots of misunderstanding here. Schering didn't provide RVR data, which means patients achieved undetectable in 4 weeks and kept it till 12 weeks. That's a huge difference between EVR, which means achieved undetectable within 12 weeks. 50-60% EVR can actually achieve SVR, but 90% RVR can achieve SVR. Undetectable means <10IU/ml. Schering has more cash than Vertex, so budget shouldn't be the reason they choose looser standard. And the reason they didn't reveal RVR data must be it is really ugly.

[Proactive]

I really can't speak for others, but my opinion of statements pulled out of ones arse "And the reason they didn't reveal RVR data must be it is really ugly." they really aren't worth the paper it takes to clean up the mess....

[Willy50]

You are right and thanks.  I "misspoke".  I think the data should have all been expressed as EVR and NOT RVR.  One reason that the stock dropped was that in one Boceprevir study the 12 week results were 79% EVR.  I believe that the Prove 1's best arm result was 70% EVR and in the Prove 2 it was 79%.

In other words they seem to have comparable EVR results.  

In Prove 1 the triple therapy arm achieved a 79% RVR but by week 12 it had eroded to 70%.  I'm not sure if that would be due to breakthrus or discontinuations.  It wouldn't surprise me if the basic pattern were similar for Boceprevir but it may not be.

Thanks for the post. I was wrong using RVR where EVR should have been used.  This is one area where the two trials can be compared.  The SVR rate will be one of real tests.  The dropout rate, the side effects, and the treatable symptoms will also be factors in the marketability of both compounds.

Presumably we'll have much more data at the AASLD.

best,
Willy

[geterdone]

http://seekingalpha.com/article/50797-schering-plough-q3-2007-earnings-call-transcript

Schering-Plough  Boceprevir

Tom Koestler
Yeah, John, as far as you know, we have this naive patient trial which is ongoing. We are looking at 24, 28, and 48, weeks of dosing. So, the Phase II trial that we have reported on, reported on 12 weeks of exposure to the program. Now we have a fast track status with FDA and as you can imagine we have got everything. We do just about right with FDA in terms of plans for going forward. But right now I think it's fair to assume that we are feeling pretty confident about the design of our run-in phase, which is the utilized interferon plus [Ribavirin] for four weeks, before dosing with a protease inhibitor. There is couple of reasons for that. First reason is that it takes four weeks to get the study state with these molecules, which is important.

You had [hit] the prime immune system and we think that priming helps decrease the viral load, and that we think is important. Also based on our learnings because we would like to be able think this would result in a fewer mutations in that particular population, which is an important clinical parameter.
John Boris - Bear Stearns
When will you start Phase III, Tom?

Tom Koestler
Okay. So…
Fred Hassan
Right now, we are not going to comment on that at this point in time. As I said, we are still on Phase II and when we are prepared to initiate Phase III we will let you know. Thank you,

[mremeet]

Thanks for geterndun on posting that excellent link geterdon. That's really interesting to read about their unique dosing strategy, I was sort of wondering why they had that quasi-odd 28 week group in the mix. I can see now what they were thinking and it sounds like an excellent idea. Preload the IFN and riba without dosing the protease inhibitor for a month. This gets the patient fully juiced and equilibriated on SOC, IFN and riba are stabilized at optimum levels first. The viral load in all likelihood will decline significantly (probably a log or 2 or more), and when the PI is finally introduced 4 weeks later, it'll be a case of instant synergy between all three drugs. An antiviral shock and awe if there ever was one. And that pharmaceutical trifecta hits just when the virus needs it least. Its breeding population is strongly eroded by then (maybe being less than a 100th of the starting VL), so its much less likely to come up with PI resistant mutants and it'll have a lot less time to do so. I imagine the lights would go out for the virus very quickly at that point. It's like spraying the virus with gasoline while hitting it with a million baseball bats. Only after the spraying is finished, a match is introduced - meanwhile the baseball batting continues. I like it, I can see the wisdom here and it sounds good.

Normally when the IFN and riba and a PI are introduced the PI does most of the eradication in the first few days/weeks. Only later do the other drugs really start to build up and activate the body's referred immune responses. But that takes time, and in that time the virus is more likely to be able to come up with PI resistant mutants. This might especially be the case for people with high VL's or relatively sluggish responses to SOC drugs. But this SOC preloading strategy largely circumvents that problem. Not sure this strategy is really necessary for those with a low starting VL (as evidenced by pln going UND on VX+SOC in 4 days flat) and generally success was observed in nearly all of us with the concurrent start of SOC+VX. But still this staged/delayed introduction of the PI sounds very good. Normally we think the faster the initial viral decline the better, but this unique tack has me re-thinking that. Also, I'd imagine this strategy may end up more reliably shortening the course of treatment as well. If this strategy does work for the reasons speculated, it may truly truncate the treatment to something less than what appears to be the new emerging PI+SOC standard of 24 weeks for geno 1 (without going into individualized treatment assessments for the moment). Anyway, thanks again for the link geter, cool schtuff.

[geterdone]

I was also re-reading the abstracts of the prove I and II of vertex and there is no mention of them pre dosing with PR before introducing the Telaprevir into the mix at week 4 but then again the whole report is not out yet. Now, if SP introduces this in there up coming Phase III trials it will be interesting to see the results but I don’t think we’ll see this until 08 or 09. Sorry for not being long in the word department to explain fully but I’m still treating, LOL!

jasper

[Willy50]

"(1)You had [hit] the prime immune system and we think that priming helps decrease the viral load, and that we think is important. Also (2) based on our learnings because we would like to be able think this would result in a fewer mutations in that particular population, which is an important clinical parameter.

It's an interesting idea.  It begs a trial both ways to see which way the virrii die off faster but it makes some sense.

If the earlier efficacy tests on Boceprevir showed that it was less effective maybe the structure of the trial provided the great results.  IF this is an effective method what will happen when Vertex does this?  Does anyone recall that Alinia also did the same thing?  I'd guess that Vertex was aware of this idea and so who is right?

Anyway..... 2 very interesting concepts.  We've discussed predosing before here with ribiviren so the idea isn't new but it's interesting to see the application with PI's.

The second part....with the mutant variants also makes some sense but we'll see how it shakes out.  If this method is a more effective means of providing efficacy or reducing the resistant varients perhaps it might also be tried in the Phase 3 Vertex trials.

Thanks for posting the link Jasper.  The link had several other references in it.  One lead me to think that they weren't going to discuss the results much at the AASLD maybe not till year end or early 2008.

Willy

[mremeet]

"It begs a trial both ways to see which way the virrii die off faster but it makes some sense."

Looks like they've already trialed both groups (i.e. 24 and 28 wk) side by side. And this guy's enthusiam and somewhat measured-coy talk suggests he already thinks this strategy has merit to it. And he already has a buttload of data in his grubby little hands right now too, so that makes his comments especially interesting. As to which way the "virii die off faster", I'm sure the initial viral decline is much faster with triple therapy administered concurrently when compared to SOC only and then the PI introduced a month later (for obvious reasons). The real questions are, how completely does this strategy expunge the remaining virus? Does it really help to prevent the rise of PI resistant variants? Will it be able to shorten treatment times beyond even what triple therapy suggests so far? Will it lower overall side effect profiles (including the relief provided by a possibly shortened treatment time) and thereby enhance adherance rates? And of course, will it improve overall net SVR rates?

"IF this is an effective method what will happen when Vertex does this?"

If it works for boceprevir, I see no reason whatsoever why it wouldn't work for telaprevir either. PI's have similar modes of efficacy and to my knowledge the general mechanism under which PI resistant mutants are evolved are the same with most or all protease inhibitors (certainly their monotherapy results share very similar rebound profiles).


"I'd guess that Vertex was aware of this idea and so who is right?"

I wouldn't be certain they were aware of it at the beginning of their phase IIb testing (although I'm sure they do now). Vertex is a little ahead of SP, and it's also probable that Schering learned of how resistant strains were being produced in some of the Vertex trial participants and therefore formulated this strategy as a possible way to nip it in the bud. Either way, it'll be damned interesting to hear more on this. This could be a simple tweak in treatment that may offer big benefits, especially for those who need those benefits most.

[willows]

I read another take on Scherings approach to dosing with boceprevir today.  Since Schering has MAJOR money tied up in Peg-Intron, if they dose up front with 12 to 24 weeks of their own SOC, they are still guaranteed the revenue stream from those meds.  My info came from an e-mail from my doc and his take was.....They may be stressing the reduction of viral mutations to PI's by pre dosing, but they are also setting up the perfect conditions for mutations against IFN.   And exposing all of us to a longer duration of SOC.  Having a few lingering issues myself from IFN that have not resolved after two years, well, I understand Doc's trepidation.  

I may be shot as the messenger bringing only the negative news, but if you read the conference call of Schering today, they were asked SPECIFICALLY twice about EVR and RVR and dodged the question both times.  This is a company that specifically avoided including African-Americans in their first trials until they got spanked.  Then they expanded and included those folks, but not until they were forced too.  I will be labeled as sooo pro Vertex that it has clouded my judgement, but I'm not really caring too much about that.  

After reading and researching for three days now, i do not believe we are getting the portions of the information we need to make a good decision about boceprevir and the patient in me wishes that our second generation PI was coming from a company with a better track record than Schering with it's Peg Intron bias.  But, like the rest of us, I will take my PI's and my tx and, with the help of the gods, my SVR from where ever I can get it.

So I'm a bit negative....I read something today I really loved...."There's a small chance I may be going to hell."  I like it, makes it easier to post and advocate information and an attitude that I know may be unpopular here.  My bias is showing, but I also hope my reading and research and due diligence is coming thru here too.  Drop SCH503034 into google and read some of the information out there.  Interesting.

[Willy50]

several points;
1)  It's really to soon to be able to make real comparisons between the two compounds.  Schering-Plough has released very little information and based on the seeking alpha article they may continue to release very little.  
The early Phase 2 trial comparisons are different design so as to make comparisons to the two compounds difficult.
The current trial designs are also different so as to make comparisons difficult.  How did they compute the numbers offered?  Was it based on the initial first doing of SOC or the first initial dosing of Boceprevir?  One would assume that it was from the first dose of any drug.  From the design data offered it's also hard to grasp exactly how the participants tapered into treatment.  The data seems to be a teaser or even a spoiler dropped right before EASL.

Whereas the trial design make it hard to compare these drugs we almost can't escape the end point data.  As surely as there was a start date there will be an end of trial response rate and SVR12 and SVR 24  data.  I believe that some people are just ending the Boceprevir Triple dosing stage now and may continue for another 24 weeks of SOC.  If so....the SVR data is a ways off

2) In spite of the news bombshell that was dropped there is so far very little information that is offered or will be offered.  There seems to be conflicting information out there about both compounds.
Vertex is allowing that while the rash issue affected larger numbers of people who treated they seem to be downgrading the seriousness of it that leads to discontinuation.
We will see response rates, discontinuation rates and SVR rates discussed at the AASLD as well as data and theory on mutations and perhaps even discussion which may foreshadow Phase 3 trial design.  

So far as Boceprevir we are fortunate to have another lead compound advance. Like Vertex, this one may not be perfect either but the are showing comparable 12 week response rates.

They also seem to have issues with resistant varients.

They also have issues with troublesome side effects and have drop outs in the most responsive arms in the teens in spite of the fact that the participants were allowed rescue drugs.  Thankfully there does not seem to be a rash issue.

It remains to be seen which compound is better.  The trial designs may continue to stymie efforts to compare the two drugs.  

The bottom line is that suddenly and thankfully we have 2 potentially great new drugs that seem to be advancing successfully thru trials.  They may be too similar to have a synergystic effect if combined (or staggered in treatment) but there could even be that potential down the road.  At the minimum we have 2 likely contenders for FDA approval (cross your fingers).

MREmeet suggested that all companies following in the wake of these developments also benefit from the scientific advances that are made during these trials.  (It may be a reason that SGP passed on a no-ribiviren arm)  Vertex's successes will also benefit the Schering research and vica versa.  The gap is being closed every week on finding a better cure.  It's pretty exciting and encouraging news.

best,
Willy

[willing]

>They may be too similar to have a synergistic effect if combined (or staggered in treatment)

I'm curious whether you've seen anything indicating this is the case. Escape mutations for  950  seem pretty well characterized "Mutations have been identified in the NS3 protease gene at positions 36, 54, 155 and 156 conferring resistance to TVR in vitro and in vivo" from aasld'07 abs 50.  but I haven't seen anything comparable for 503034. If different  mutations at different amino acids are involved, I would think the virus would have to develop both to obtain a viable NS3 protein. Given that its search  is basically limited by the error rate of the viral polymerase and the amount of replication, I'd expect these to be additive.

(also there's some promising information on r1626 mutations in abs 1298)

[jmjm530]

This thead certainly has its share of willpower.

[Willy50]

I've seen that resistant mutations may also be a problem for Boceprevir too but that's not much of a stretch.  That Darn Virus (that sounds like it could be a fun movie title) seems to mutate around everything.  

I based my theory that they may be too similar to be synergistic based on they are both PI's and share other similarities. They may be like Peg-Intron and Pegasys; similar but not quite the same.  This is one area that I'll just say no clue.  (They both end with "previr" too.  : ))

On the other hand..... There is at least one presentation at the AASLD (but you probably already knew that) which could shed some light on the topic.  I'd guess both companies know or have theories.

On the back side of the other hand...... if Vertex knows something that could help their "comrade in arms"....SGP, I wonder if they would post a paper on it.  They may already figure they've done some heavy lifting for their competitor.  It kind of reminds me of drafting in a bike race.  If Schering watches Vertex they can save themselves some money and learn from the mistakes or discoveries illuminated by the Vertex trials.  I mean, I wonder if the Vertex no-ribiviren arm had been more successful would have SGP had a variation on the same theme?

Getting back to the crazy issue....maybe this is the wrong thread for it but what happens if the Vertex prior treatment failure trial (also known as Prove 3) comes close to the results of Prove 1 and 2?  I don't understand (yet) why the naives seemed to do so well in the Boceprevir trial and the treatment failures trial seem to have a poor response rate.  So far the Vertex Prove 3 participants seem to be attaining an RVR and maintaining that status till treatment end.  I wonder where the failures in the Boceprevir trial occur?

Oh yeah....tying that thought to the title of the thread....... what would success with Prove 3 spell for the stock price?  Likewise....do we look to the poor results of the Boceprevir harder to treat group as what we can expect of Telaprevir Prove 3 results?  (I suppose that may deserve a different thread and may soon be answered by the Prove 3 results as they roll in.  They are sure looking good so far.)

Willy