Telaprevir Launch Could Be Delayed to 2012

This sucks!

http://money.cnn.com/news/newsfeeds/articles/apwire/da3e9a9e4c40232cc4c40734b0762a6c.htm

[charm27]

Thats certainly does. I guess my hepatologist was right and I QUESTIONED HIM. He said he earliest would be 2013.

Sucks!
Charm27

[gauf]

My Hepotologist was right too!

[mremeet]

I wouldn't put too much "stock" into what George Farmer the "Wachovia analyst" says. Half the time these analysts don't know their a$$ from a hole in the ground, and the other half of the time they're trying to pump or dump a stock price for their own benefit (or more precisely for the benefit of their clients). No one really knows how long it will take for Telaprevir to come to market. Technically it's a true statement to say it could take until 2012, and technically it's true to say it may never come to market. But it's also true that it could be approved within 2-3 years. I haven't heard anything new from Vertex or the FDA recently to lead me to believe all of sudden the phase 2 data is "bad" and now it all has to be "redone." Here's some facts from a guy who's taken Telaprevir: it greatly assists in CURING people with HCV - it WORKS, side effects can be bad but the vast majority tolerate it well, Telaprevir is currently entering the final phase of testing prior to FDA approval (phase 3), no long term negative side effects or toxicities have been reported by Vertex, the FDA, nor experienced by anyone on this forum (and there's quite a few of us here now). And all this is coming from someone who got the worst side effects imaginable from Telaprevir. I've got no dog in this hunt (unlike George Farmer), other than wanting more people to be able to access this drug ASAP so they can be cured of this terrible disease. And charm if your doctor says that he knows for a fact that it'll be at least 5 more years minimum before FDA approval??? That's absurd, he can't know that, and unless he's sitting on "secret info" that justifies that claim, he's in all likelihood dead wrong.

[charm27]

I know exactly where your coming from and what your saying. I really do. I was going to postpone tx and wait. I had asked him  He's Dr. Schiff's partner at U of M> All he said was at least 2013 until it all gets FDA approved give or take a year. So I decided to treat.
He explained if I treat now I would be interferon resistant and could not use the new drugs coming up inthe next few years. So.....I decided to strike while the iron is hot and let the chips fall where they may after hearing that.
Im treating now.
Its just a big question mark in my mind and an annoying one. We shall see.
Charm27- I just pray its sooner than later like everyone else here.

[Bill1028]

I would like to know why he thinks boceprevir will be approved sooner.

[nygirl7]

This is exactly why most of us do treat right away - I mean granted it would be nice to have an 'easier', 'shorter' course of treatment but waiting for something that might not come to be is dangerous dangerous business.  

I wonder if something else will come out better than boceprevir or tele in the meantime?

[nygirl7]

"We believe the PROVE trial dropout rates support further Phase II dose exploration before justifying Phase III advancement," Farmer said.

---

Is this because of the rash are they saying?  

[3txsofar]

Wachovia, which Farmer works for, is  a 'market maker' in Vertex stock.  Thus, the more Vertex shares trade, the more money Wachovia, which is hurting badly due to morgage losses, will make.  

Given that there is no new news, is it possible that Farmer is creating some business for Wachovia?

I stick to my prediction - Telaprevir approved by end of 2009.

[can-do-man]

Happy New year all !!!!!!!!!!!

Little confused here, which BTW doesn't take much.

charm27         He's Dr. Schiff's partner at U of M> All he said was at least 2013 until it all gets FDA approved give or take a year. So I decided to treat.
He explained if I treat now I would be interferon resistant and could not use the new drugs coming up inthe next few years

So is it Dr. Schiff's staffs belief that once you tx. and you relapse you won't ever be able to tx again?

Cando can't think clearly anymore

[charm27]

I can re-treat with SOC BUT he claims not with the new drugs. I dont understand it-I dont claim to understand it and it got me down for quite sometime- We discussed this four times and thats what he advised me.
I cant think clearly on that subject either- I had to put it out of my mind or go nuts.
If I relapse early in tx I can wait and treat with new drugs. But NOT if I relapse 3-6 mos after tx.

I still hope and think something will give its has too. Look how many people that have relapsed and are waiting for new drugs. Like I said me & the doc discussed this four separate times and that was he advised me. Interferon resistant issues.

[jmjm530]

The stock has been dropping for over a week now which makes me think that the Wachovia analyst has leaked the report in advance for whatever reason. Hopefully, he's wrong, because we could use somethig better than SOC  alot sooner than 2013. I've heard '09 and '10 from some major trial doctors, and now repofrts from Schiff of 13. Sounds like a lot of guessing right now. Fact is that they got 60% SVR in only 24 weeks without helper drugs. Let's hope that sinks in and the FDA gives a quick thumbs up.

-- Jim

[3txsofar]

It's not technicall leaking.  You send it to your own clients and then later release to the press.  

Another factor to consider is that since Wachovia is a market maker they can do 'naked shorting'.  Which means the following scenario is entirely possible: a, sell a lot of shares you don't own; b, release new rating to clients and then press; c, watch VRTX fall, and d, buy back shares for a tidy profit.

[Andiamo1]

I treated 7 times with various flavors of Interferon and Riba. Now I am in the 48 week arm of Prove 3.  I became undetectable in two weeks, so previous treatment with SOC definitely does NOT make you resistant to Telaprevir.

All the publishes statistics on Telaprevir that I have read show dropout rates similar to Boceprevir.  I think this analyst is full of it and he does not back up any of his statements with facts or studies.

How can you say a study is flawed and not say why?  why has the FDA remained silent on this.  

I know for a fact that Vertex is now recruiting medical centers to participate in the phase 3 trial to start early this year.

Eric

[nygirl7]

**** I just wrote all whole GO ANDIAMO GO post and when I went to hit send I saw you posted over me LOL.  Now I lost my whole post (but am glad to because you're still doing GREAT!)

I guess their thinking maybe is that there is a great chance of the virus mutating and it might not work. Who knows. What will be will be and all we can do is wait and see.

[willows]

Mr. Farmer has a stake in both the long and short of Vertex, so if he can't make his money now because Vertex stock won't go up, then he uses his "analyst" clout to make the stock price drop just a tiny bit and THEN he makes his money.  

None of the fundamentals of telaprevir have changed, the pharma of it is still looking so good, as good as SOC in half the time.  No analyst can spin those numbers any other way.  The news kind of knotted my bonnet this morning so I did a little research and found......absolutely nothing had changed.  Except Mr. Farmer's opinion.  Wachovia and Mr. Farmer were HOT for Vertex about 10 months ago, at a price almost twice it is now.   My liver and I hate "fabricated" news like this article, but it goes away quick.  I just find my happy place and recalibrate my perspective of fools and foolish market news like this.

[Aquila]

My theory FWIW is that the Tibotec phase 2 trials in Europe of Telaprevir  ...  

http://www.clinicaltrials.gov/ct2/show/NCT00528528?term=telaprevir+tibotec&rank=1 ...

that are only just starting to recruit and are even expanding study locations could be the expansion of phase 2 studies that the market suggests is necessary.

"We believe the PROVE trial dropout rates support further Phase II dose exploration before justifying Phase III advancement," Farmer said.

The dosing protocol for the new studies are:

"There will be 4 treatment groups: 12 weeks of telaprevir 750 mg every 8 hours + 24 weeks of Pegylated interferon alfa 2a + ribavirin; 12 weeks of telaprevir 750 mg every 8 hours + 24 weeks of Pegylated interferon alfa 2b + ribavirin; 12 weeks of telaprevir 1125 mg every 12 hours + 24 weeks of Pegylated interferon alfa 2a + ribavirin; 12 weeks of telaprevir 1125 mg every 12 hours + 24 weeks Pegylated interferon alfa 2b + ribavirin."

I'm interpreting that to mean they are all 12+12 week treatments with just different dosing regimes of Telaprevir.  These are all followed by 24 weeks post-tx monitoring for SVR.

Perhaps they are hoping the different dosing strategy will assist with the rash and drop-out rate although one would think that a higher dose twice a day would do the opposite.  It could make the rash worse but make treatment a little "easier" if the TVR could be taken with the RBV.

All speculation until Vertex tells us something.  

"If there is no announcement from Vertex before New Year's, investors should look next to the closely watched and well-attended JPMorgan health care conference in San Francisco, which kicks off Jan. 7.

"Vertex has used the bright spotlight of the JPMorgan conference to highlight telaprevir in the past. You can bet the company will be inundated with anxious investor questions in January if there's no update on the telaprevir phase III study before then. "

From TheStreet.com   11/7/2007   http://tinyurl.com/2kx9zc

[GoofyDad]

Let's talk more about this idea of not being able to treat with PI's after an SOC relapse. Whassup with 'dat my peeps?

It sounds like the fear-factor here is the theory that the post-relapse viral populations would be rich in quasispecies that are stealthed against the Interferon-amplified innate immune response. My understanding is that these bugs would be less fit for replication than wild-type, and the viral/quasispecies load would soon return to a pre-tx blend after serum viral load reentered detectible ranges. But the virus would remember how to quickly stealth again when attacked again in the future.

Sounds right so far?

So if all this is true - why do SOC retreatments work? I would think they would be less potent against the re-emerged and educated virus than would be a PI enhanced shock-and-awe attack. So there's the bit I don't understand - how does SOC retreament stand an acceptable chance, but not a PI-combo?  Anyone have any insights on this. I'm sure there are plenty of relapsers interested.  

[willows]

From what I can remember, there was a post here a while back, from someone who had attended AALSD.  This person, I cannot remember who, told about a group of doctors, separate from the main convention, who were meeting "down the street" and telling folks that relapsers and vl breakthru folks like myself, anyone in fact who had been profiled as "interferon resistant" would not benefit from telaprevir and SOC.  Now, in my mind, this was a pretty sweeping statement to be making and if I remember correctly, there was NO substantiating facts from those same docs as to why us "interferon resistant" folks would not benefit.

Could be that telaprevir needs the inf to whack the virus after telaprevir has kicked butt early, EVR and for a SVR, the long term IFN effects are needed.  But my doc at the time had NO info about this meeting of "concerned" docs and their "generous" sharing with investors, journalists, etc., and he still believes it will be 2009 and that I will be as good a candidate as any other SOC drop out/kicked off/viral breakthru/non-responder.  

Seems like there was a bit of a buzz here for a while about the news out of the conference and like you said, some very interested relapsers posting, but I have never found any corresponding data anywhere else.  So I hold my breath until January 7th, may be some news coming from Vertex out of the JPMorgan healthcare conference.   Andiamo says he's seen evidence of phase III starting, I believe him and my hope is always springing eternal around here.   Just takes a quick gut check and I remember my CONVICTION that telaprevir works at least as well as SOC and in half the time.  Just wish the whole darn thing would hurry up........

[Forseegood]

excellent posts. Your reasoning sounds reasonable to me.

[willing]

makes no sense to me. As best I know vx's mechanism of action is way simple: bind to a specific pocket of the virus's NS3 serine protease and thereby stop it from doing its job. The effect is to  more or less immediately block replication of all virus except those which had the foresight to evolve an NS3 variant to which vx can't bind. A handful of such mutations have been identified and it seems one or two amino acid substitutions are sufficient,  an easy trick for HCV to pull off. IFN on the other hand whips up all kinds of  complex Rube-Goldberg-like machinery capable of eliminating a much wider range of virus.

Quite possibly I'm just misinformed but I can't see any reason to keep relapsers away from combo tx. On the other hand I can see why Vertex may not be interested : something has to kill off the easily selected vx survivors. If ifn failed for you the first time it may also fail to eliminate this smaller population: lower SVR , bad for the stock price.

charm: I respectfully submit you should go talk to another Dr. Any physician that can't explain the difference between what he knows with some certainty versus what he is speculating about is wasting your time.

[Andiamo1]

If you break the treatment failures into relapsers and non-responders, I think the relapsers are doing very well in the prove 3 trials.  All the people in Prove 3 that I am aware of and ended up on triple therapy have responded very quickly as I did.

Those in the 24 week arm that reported here said they were still undetectable at 4 weeks post treatment.  I am seeing one of the top hepatologists in the world and he believes that relapsers have a very high probability of SVR with Telaprevir.  Perhaps they will have to treat for 48 weeks; that is what the Prove 3 trial is attempting to determine.

[Xenigma]

U of M docs also told me 3-4 years ago to wait for new drugs. (Schiff)
Then 1-2 years ago (Dr. OB - from U of M) said I wouldn't be able to use new drugs and
to tx now.  I asked why and no real answer was given.  (I thought this pertained to just me)

I didn't like when Sch tells me one thing and then
Dr. OB tells me another and then get's
PO'd when I start asking questions as to their diff of opinions.

When they conflict, I lose my confidence in them.

I found a doc willing to tx me, actually I found quite a few,
picked one I liked and am UND.  Even these Docs couldn't fathom why the team at U of M
came do that decision and were conflicting.

They all said that if I happen to fail tx, there is no reason not
to try again. (even when new drugs come on the market)

We all hope that new drugs are right around the corner,
but each year we hear that, and still, none are here,  so
decisions have to be made.

What we got is what we got.  Each and everyones decision to tx now or wait
depends on many factors. (And it's very personal)

I chose to tx now because:

Bx 1/1  minimal damage
Extra hepatic manifistations were getting much worse.
Post menopausal, and VL (which was always between 700k-1.2m)
shot up to around 5m now that I am post-menopausal)
I felt my body fighting harder and harder to keep
the virus at bay. Too much pain, fatigue etc...
I couldn't live like that anymore.

Many with my stats would have waited.
It's a crapshoot, and I took a chance.

enigma

[Proactive]

I'll say it again.....Keep your eye on the fda regarding amemia drugs....While not talked about here much, except in the light of their benefits...(some even continually bring the subject up in regards to vx950 trials and better numbers)..the fact is the fda is clamping down....this needs to be weighed heavily with regards towards new hepc drug approval...The argument of.....well if helper drugs had been allowed......kind goes out the window...and as I recall vx950 treatment had an increased  anemia profile...so the fda may scrutinize (?) a bit more in the approval process.
http://health.usnews.com/usnews/health/healthday/080103/fda-reports-new-risks-posed-by-anemia-drugs.htm

[willows]

Interesting article, I understand a bit better about the concern around the anemia drugs now, but have to wonder.....wouldn't the change from 48 weeks to 24 weeks help aleviate some of the problem?  Crumbs, I hope so, with so much stacked against some of us, we need all the help we can get at this time.   Maybe with a combination of tweaking doses of riba and more rest, we could get past the anemia thing, and if it is only for 24 weeks, I'd be willing to run the risk of needing a blood transfusion.  Seems like taking more care while on tx would be a good answer.

FDA will be interesting to watch and I guess if it starts to look like 2012 or beyond, I can always give SOC a try again.  Doc gave me about a 20% chance for success, but like Xenigma, I'm getting tired of being tired.  I can watch telaprevir til 2009, then make the decision.  But good info like yours always helps.

[jmjm530]

Fortunately, that is not new news, and liver specialists are still prescribing after weighing the risks and rewards. That said, while I have mentioned the helper drug thing in terms of the Telaprevir trials, I mentioned it more as icing on the cake, not as reason for FDA approval. Currently, without helper drugs, Telaprevir is showing 60 per cent SVR rates with half the treatment time of SOC (24 weeks). This alone, seems to me impressive enough for a timely FDA approval. Helper drugs can only help better the 60 per cent rate -- not to mention if they come up with a rash solution -- but again do not seem critical for FDA approval.

-- Jim

[frijole]

From Clinical Care Options -- This is a very good module on who will benefit from retreating.  If you (relapser/ nonresponder, etc) have a little time, I recommend it.  It does not deal with new drugs but is a good read and has good graphs.
frijole

http://clinicaloptions.com/Hepatitis/Treatment%20Updates/HCV%20Nonresponders/Module/Shiffman/Pages/Page%2013.aspx

If anyone has a little time,

Summary of Clinical Implications
A patient must respond virologically and achieve undetectable HCV RNA (< 50 IU/mL) to achieve an SVR.
Patients who do not respond virologically cannot achieve an SVR by continuing the same treatment for a longer period of time.
Patterns of virologic response and nonresponse be recognized by assessing HCV RNA at monthly intervals until the HCV RNA has become undetectable or a nonresponse pattern has been defined (Week 24).
Up to 90% of patients with RVR achieve SVR if they remain on treatment for 48 weeks for HCV genotype 1 infections and 24 weeks for HCV genotype 2 and 3 infections.
Rates of SVR in patients with genotype 1 infection who achieve an RVR do not appear to be affected by reduction of ribavirin dose.
The initial management strategy for patients with RVR who develop adverse events should be to consider reduction of the doses of ribavirin and/or peginterferon alfa so that these patients can hopefully complete the recommended duration of therapy.
It is important to continue to monitor HCV RNA through Week 24 even if the patient does not achieve undetectable HCV RNA during that time to allow for identification of partial virologic response.  
It has been hypothesized that some patients with a partial treatment response may achieve undetectable HCV RNA if switched to or retreated with a more intensive peginterferon alfa regimen.
Patients who do not achieve an EVR will not achieve undetectable HCV RNA with continued treatment and are defined as having a null response. This is an indication for stopping treatment.
An important reason for viral breakthrough may be missing doses of peginterferon alfa and/or ribavirin.
Patients fail to achieve SVR for several different reasons. All but one of these factors, null response, can potentially be overcome during retreatment.
Only those patients who have a known and correctable reason for their previous treatment failure should be considered for retreatment.
The outcomes of retreatment may be maximized by improving education and awareness about adverse effects of peginterferon alfa and ribavirin, having a stronger commitment to therapy, or seeking care from a more experienced and/or attentive treatment provider

[jmjm530]

Thanks for posting.

Fri: All but one of these factors, null response, can potentially be overcome during retreatment.
-----------------------

Not sure if this contradicts anything, cause don't have all of it in front of me, but
another module at Clinical Care Options suggests that double-dosing might be a re-treatment strategy for null responders. I believe it's "Doc Eye for the Hep Guy". And then there may be other interventions such as higher-dose ribavirin or some of the newer PIs in trial.

Fri: Patients who do not achieve an EVR will not achieve undetectable HCV RNA with continued treatment and are defined as having a null response
-------------

Fom memory, because I did read this recently,- I believe that the definition of "null response" in addition to the above, has the assumption that full meds were adhered to. In other words, one could not achieve an EVR but still not be catergorized as a "null responder" for retreatment purposes -- that is if full doses were not adhered to, since the question would remain would they have responded on full-dose meds. In that case, the re-treatment strategy would be to try and address why full doses weren't adhered to, such as treating anemia with Procrit (epo).

If I haven't already, let me wish you a happy and healthy New Years!

-- Jim

[FlGuy]

There are a lot of differing opinions out there, even within the same practice.  As a relapser, I went to one of the other UM docs who came up with a protol (variation of doses and duration using Riba and Ifn) that got me through to a happy ending.  I also inquired about new drugs, specifically VX, and was told to get on the TX bus immediatiely (early cirrhosis) since inclusion in VX trials for G3 relapsers was pretty far down the road.  As patients, sometimes the best that we can do in the face of conflict is to learns as much as we can and make the best informed decisons we can.  Someone once remarked on this Forum that treating HCV, with all it's variations and premutaions is sometimes as much art as it is science.

[Xenigma]

As patients, sometimes the best that we can do in the face of conflict is to learns as much as we can and make the best informed decisons we can
-----------------------------------------------------------------------------------------
Yes, I totally agree.
I just didn't like that within the same practice, a difference of opinions.
(Which wasn't explained as to why)  I need to have open
communication with my docs.

I must say though, if anyone ever needs to get a 1st, 2nd, or 3rd opinion,
I still highly recommend U of M.  My years going there were not wasted,
but in the end, I decided to treat and not wait.

[Andiamo1]

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Thursday January 3, 9:15 am ET

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[mremeet]

I took telaprevir for about 7 weeks along with IFN and riba. Then stopped the telaprevir and continued on with SOC for another 34 weeks. My riba dosage was significantly and persistently curtailed and even interrupted for a while during that timeframe (due to skin issues). I only took a single shot of procrit, so it really played no role in my treatment. I went on to SVR just fine with suboptimal riba dosage during an abbreviated tx duration (7 weeks shy of 48 weeks). I also took gobs of immunosuppressants like prednisone and solumedrol (things that could make you fail treatment). And again, I SVR-ed fine with the help of VX950. Pam (PLN) is another VX950 trial participant. She had her riba cut in half early in her treatment (by week 2 or 3) and she remained on half riba dose throughout the remainder of her 24 weeks of treatment. She went UND by day four and went on to SVR just fine as well (and remember that's with only 24 weeks total treatment). There are many others with similar treatment histories.

Telaprevir "bends the wing" of standard SOC treatment dynamics. It reduces the importance of optimal riba dose levels. If a patient becomes overly anemic or experiences gnarly skin issues (as I did), as often happens as a consequence of ribavirin, as you can see from what I've described earlier the patient can often get away with reduced/sub-optimal ribavirin dose. I suspect it's best to not reduce ribavirin dose until after UND status is achieved, but that's usually not a problem because it takes a while for the riba to sink in anyway (the vast majority go UND within 2-3 weeks when SOC and VX950 are dosed together). And as far as telaprevir actually causing anemia, as far as everything I've anecdotally learned and personally experienced, telaprevir is not a big contributor to anemia at all. Its effects in regards to anemia appear slight in everyone that I know of (including myself). I don't know of anyone who stopped telaprevir, but continued on with IFN+riba and then suddenly had a big rebound in HgB. Telaprevir's impact on anemia seems light and very manageable from everything I've seen (although yes it has been reported to have some effect on HgB levels).

Anyway, even if the availability of procrit was curtailed by the FDA for the purposes of treating anemia associated with SOC tx, if telaprevir is brought into the picture this needn't be an SVR damning event. Telaprevir can really make the difference, even in halfed tx durations and even with sub-optimal riba dosage.

[willows]

Hooha!  I love reading posts like yours, helps me "bank" more hope....carrys me thru the down days and the tired days and the sick days.  Especially when you concur with everything I have read and researched and remember from the months here while you ALL did the lab rat thing.  I could never let myself consider "SVR" until the trials for telaprevir started, now...my hope account stays fat enough to keep me going.  Thanks!

Willow

[lab-rat]

As a relapser of prove 1 (SOC) - your posts regarding the chances of relapsers re-treating w/ vx caught my eye.  I'm eligible to join the rollover trial, (and get the real thing this time) however my study Dr. did not recommend it since it's only a 24 week trial (12 wks of telaprevir w/ 24 wks inf + riba).  His opinion was that I should re-treat (SOC) for 72 weeks and was concerned about chance of mutation.  Or that I wait for a trial of longer duration.

I decided to join the rollover trial anyhow (hopefully not a big mistake) - and that doctor thought I was making the right choice.  Only time will tell..but she did say that she would do it if she were in my shoes (after I decided to join)...and also that most trials are just not available to relapsers.  The chances of getting access to a new drug is greater for someone who is treatment naive.  

[willows]

All the concern about chance of mutation is so murky to me....if I had a chance to try telaprevir for 12+12, I would go for it too.  Good luck to you.  SOC for 72 weeks is not covered by protocols anywhere...plus, so many folks have had good luck with telaprevir at just 12 weeks.  I'm not sure we will ever see dosing for telaprevir for any longer than 12 weeks anyway.  As far as extending SOC into 72 weeks beyond the 12 weeks of telaprevir...why can't a person do that now?  

Again, good luck to you...we'll be here wishing the best for you.

Willow

[scratchinghead]

thanks, for whatever reasons.

[lab-rat]

Thanks willows  I've also considered that if I really wanted to, I could drop out of the study at 24 weeks and extend SOC treatment on my own (not sure if I could get any insurance to cover that).  But I guess I'll cross that bridge when (or if) I get to it!

[FullOfHope77]

I too had a lot of issues in ARM B of the study and couldn't/didn't do the last 5 days of 24 weeks of Telaprevir just pschological I think. I had the rashes galor but after stopping and treating with creams the rashes slowly disappeared. i'm only in week 31 now and do have the 'feelings' of anemia that I haven't had before during SOC and it's requireing me to work from home due to feeling like I'm dizzy and shouldn't drive but that's a confidence thing and I have someone who can drive me when I need to go somewhere.

So, I have all the situations covered and feel that if this works like it seems it will (I was RVR at week 3) probably week 2 but after 2 full treatments I was UND; then I feel it's ready and worth making it available to the masses and feel like thousands if not millions are getting ripped off all for the wrong reasons.

I thought about investing in the stock while so cheap but the PR is so misleading I'm afraid it will go down and have to wait it out even longer while it finally works itself out of the anaylst hail. If I don't invest and it goes up then I will really feel stupid but most importantly this is not about the money it's about the people that can benefit sadly that seems to be forgotten during these times.

Scotty

[Bill200]

Hey guys just wondering what genotype y'all are?  I'm 1b and have failed to clear in three treatments.  So when you guys say you cleared I'm wondering about your history.  I'd like to do telaprevir but they so far won't let previous non-responders join yet.

[Susie2007]

"He explained if I treat now I would be interferon resistant and could not use the new drugs coming up inthe next few years"

I believe this is what the doctor meant. If you treat now and you do not respond, treating later with telaprevir or other PI's plus interferon, will not work for you. If you wait and use the telaprevir with your first try on interferon (treatment naive patients), the PI's may be enough to allow you to SVR. If a non-responder has complied perfectly, not had any dose reductions, and never had a 2 log drop, he is resistant to interferon and adding a PI will not work. Why it would work with a PI the first time is unclear to me. Perhaps HR would be able to explain.

[fightit]

I would like to know the answer to that also. According to some, even treating nonresponders with higher doses of interferon or ribavirin will not work.
I am very interested in the results of the telaprevir trials with nonresponders. I guess we will have to see 3 or 6 month post treatment results.

[Andiamo1]

For the umpteenth time!!! I have treated 7 times with SOC prior to entering Prove 3.  I was undetectable at week  2!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! Does that sound like I am resistant??????????????????????????????????????????????????

[dointime]

Seems like there's a lot of confusion about this.  Lab-rat is a RESPONDER.  Lab-rat did 48 weeks SOC and relapsed post tx.  Lab-rat please correct me if I am wrong.  

So interferon resistance is not the issue.  Telaprevir resistance is the issue.  
Well, that's how I read it.

dointime.

[Willy50]

I keep telling people about you, also the fact that you are 65ish and presumably have diminished immune response and yet you cleared handily and have so far stayed clear.  Indeed....that has been the pattern for about all of you RVR (triple therapy) responders in the Prove 3 trial.

Strictly speaking your results speak to the issue of interferon resistance, not resistant virii to the PI's.  The issue is that according to the studies....or what I have gleaned from peoples descriptions of them that there are "null" responders.  These are people with very poor response rates with interferon.  Technically, if you responded in the past you could still have failed TX but not fallen into that category.

One thing I see on this board is people perhaps misinterpreting the studies.  I mean, I think the issues may exist but not in all people who have failed TX.  It may also exist soon after treatment but it may become less of an issue over time.  Just as bugs didn't immediately become immune or resistant to DDT overnight the virii may not forever and irrevocably become resistant to IFN.  This does not mean however mean that the principle involved is invalid.

I think when telaprevir is added to the mix it will tend to trump any IFN resistant virii.  The issue however may remain for people who have to quit triple therapy treatment prematurely and who do not succeed may have to find stronger treatments to overcome resistant strains of HCV.  I think many of the principles involved with resistant bacteria and antibiotics will be seen in TX and HCV.

Best wishes by the way on your remaining TX and ultimate success.

Willy

[Andiamo1]

My Doc thinks that the issues with relapsers regarding SOC are not related to the virus becoming interferon resistant.  He says that interferon does not attack the virus directly, but rather indirectly through our bodies own immune system and cell defense.  The effectiveness of interferon is dependent on our bodies ability to deliver the interferon to the effected cells and the ability of our cells to use it.

PIs directly attack the virus and eliminate all but resistant virons quickly.  This does cause resistance and interferon and ribaviron are required to eliminate the resistant virons.  People with marginal ability to react to interferon do better with a PI in the mix.  People who were null responders to interferon simply can't eliminate the mutant virons.

This seems like a reasonable explanation to me as to why relapsers on triple therapy all seem to respond very well to Telepravir.

I was only trying to counter the arguments that taking SOC once will make it impossible to treat with a PI.  This is simply not correct.

[Andiamo1]

And thanks for the best wishes!

Eric

[jmjm530]

Is your doc then saying that EVRs  on SOC (two log drop by week 12 but still detectible) who relapse will potentially do well on Telaprevir triple therapy

-- but that previous null-responders (<2 log drop at week 12) will not respond when re-treated with triple therapy?

---------------------------
If the latter, I wonder whether they will use the <2 log at week 12, as the cut off for null-response, or how they will fix that point?

Also, I've seen the term "interferon resistant" at times used somewhat synonmously here with "null response" -- but in fact there may be other reasons for null response, for example under-dosing with ribavirin.

If ribavirin underdosing is the reason for null response, then I assume that even this particular subset of null-responders could benefit from triple therapy -- Assuming, of course, that they can be identified,  as opposed to those who are truly interferon resistant.

-- Jim

[jmjm530]

First sentence should read in part:

"... but that previous null-responders (those without  a two-drop at week 12) will not respond when re-treated with triple therapy?

[Willy50]

I don't claim to understand to understand it completely.  I think that they are still trying to get a handle on quantifying exactly what it does mean.  I agree Eric, it seems as if many people are simply equating the principle to mean that if you've treated with IFN in the past that you are "resistant" and that is just not so.  

I think that it is also true (so this is me expressing an opinion or what I think I understand) is that even if one were to be a null responder that if one were to treat with a more potent form of treatment (for example with triple therapy TVR or Boceprevir) that one might still overcome the IFN resistant virii.  If one had a group of 100 "null responders" the results might have a spread of results some failing completely, some failing but barely, some succeeding but barely and some succeeding perhaps even with RVR's.

It's all conjecture at this point I think but it will be less in conjecture once we get the results of the Prove 3's.  The results have yet to be posted by Vertex but those that we've seen here on the membership suggest that past treatment failures respond to triple therapy and do so in a manner never seen before (and perhaps not seen in the Boceprevir trials as well).

Getting back to the main topic of the thread I believe that if the Prove 3 results are strong it should have a tendancy to keep the trials moving forward.  A speedy trial and an effective treatment for prior failures should also equate to a raise in stock value.  (obviously the opposite will also impact on stock price)

Willy

[Andiamo1]

I mixed my own conclusions with the Doc's.  Sorry about that.  His conclusion is that SOC fails due to our bodies inability to either deliver the drugs or our cells to process them properly, not due to interferon resistant virons.   He also believes that relapsers stand a better chance with PIs than non - responders.

My observations of people in  the prove trials seem to bear that out.  I am not aware of anybody on triple therapy that was a previous relapser that did not have RVR.  It there are any here, I hope they respond and give us more data.  If there are any non - responders that experienced RVR on triple therapy I hope they comment here as well.

Jim: your effort to relate previous SOC treatment to probability of success with PIs through test results is admirable.  I don't have the information to back that up or negate it.  I think that will be an outcome of the Prove trials.

Eric

[Andiamo1]

I had a two log drop by week 12 and undetectable by week 24 on SOC.  Is that considered EVR?

[mikesimon]

A 2 log drop or undetectable by week 12 is classified as EVR. The newer thinking based on studies is that complete EVR (undetectable by week 12) or cEVR is more predictive of achieving SVR than EVR so, perhaps we should alter our thinking and our decision making with that distinction in mind. Good luck to you, Mike

[Willy50]

Agreed with Mike.  You qualify for an EVR by either account.  Frankly, wouldn't you be an RVR as opposed to an EVR?  After all, you cleared and stayed clear by week 2. (the qualifier for RVR is @ 4 weeks)

By the way....there is a Vertex teleconference today at 4 pacific time.  I hope they give us a little insight into what's going on.

Best,
willy

[Willy50]

http://biz.yahoo.com/bw/080107/20080107005882.html?.v=1

Vertex Pharmaceuticals Reports Progress in Development of Investigational HCV Drug Telaprevir and Provides Business Update
Monday January 7, 8:01 am ET  
- Formal European scientific advice obtained for telaprevir development program -  
- Meeting scheduled with FDA for January 2008 on Phase 3 trial design and recent data -  
- Next-generation HCV protease inhibitor and two investigational compounds for cystic fibrosis in clinical development -


CAMBRIDGE, Mass.--(BUSINESS WIRE)--Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX - News) today announced its key business objectives for 2008 and provided an overview of recent developments, including highlights from research and development programs, in conjunction with the 26th Annual JPMorgan Healthcare Conference in San Francisco. At the conference, Joshua Boger, Ph.D., President and Chief Executive Officer, and Kurt Graves, Executive Vice President, Chief Commercial Officer and Head, Strategic Development, will today review Vertex’s HCV product development and commercialization strategy. A live webcast of this presentation will be available on Vertex’s website, www.vrtx.com, today at 2:00 p.m. PST (5:00 p.m. EST).
--------------------------------------------------------------------------------------------------------------

The article is too long to post but it is juicy and worth a look,  Boger does the presentation today and they also mention that they started dosing with VX-500.  Looks like it will be a good presentation.

Willy

[Andiamo1]

The stats I was referring to were for my SOC treatment prior to the Prove 3 trial.  On SOC, I continued undetectable until EOT and then relapsed after one week off treatment.

On prove 3 my viral load dropped from 8.2 million to <30 in one week and undetectable in two weeks.

Eric

[Willy50]

Ooops,  you said it clearly but I missed it.

[merryBe]

I just hope all those "naked shorters" realize one day they'll stand naked before..... Him....with no shorts, or jockeys either, to protect them....  : ))))))))))))))))))))))))))))))))))))))

[Andiamo1]

I just listened to the webcast; Vertex has hired a senior exec from Novartis to take Telaprevir to market and he gave the presentation.  Not much technical meat to it, but he did say that they are in advanced discussions with the FDA for phase 3 approval and that they are even further ahead in Europe.  He also mentioned VX500, the follow on drug to Telaprevir, is already in phase 1 trials.

It certainly looks like most analysts don't know what they are talking about.

[merryBe]

I think mr meets point was, most analyists don't CARE if they know what they are talking about.
they aren't being paid to care, only to make speculations and prognostications to drive market shares.
Drug approvals are highy speculative, meanwhile there's book to be made on the timelines.

If you understand traders, they trade on, and manufacture for trading purposes, both good and bad news....good or bad matters not...only something to trade TO trade on.
the market goes sideways and they still make billions...the ultimate spin doctors, it's all about the sell...knowing where the lemmings will all run to next....(because you told them which cliff to run off) and then getting there first yourselves.

[Andiamo1]

Much as I hate stock analysts and think they are sleaze, I  am aware that they are judged and financially rewarded based on the accuracy of their forecasts.   The success of a drug or the company itself is irrelevant to them; only the direction of the stock price means anything.  If an analyst downgrades a stock and the price subsequently drops, that is all that matters.

So I guess I mostly agree with you both with some differences based on my personal experience of going through an IPO of a telecom company during the go go days.

[lab-rat]

Thanks for clearing up my confusion.

dointime - you're correct I'm a relapser and I did respond to interferon.  I was getting confused between the difference in odds of non-responders v. relapsers treating with PI's.  I tend to skim over a lot of the information (which can do more harm than good).  

Andiamo1 - I can't believe you've treated 7 times!  I'm so glad to hear that this seems to be doing the trick for you - you're giving me hope.  Thanks and good luck!

[merryBe]

bad news in medical stocks is very good news to a select few.....
a common term, bottom feeding, is where my profits were often in excess of 100% in a matter of days. The trick was knowing how seriously the street would take the news, who concocted it, and what the real base line financials and research stats were. Then you estimate where the big financials and the lemmings (individual investors) will jump with that.
It's rather like trading IPO's except you can get in when the banks do, and without buying a thousand blocks at a time.  Just don't put too many eggs in either of those baskets unless you know the risks,

congrats on your improvements by the way, you may the case well, as to relaspse retreatment.
Even if you VL went up a tad after being UND....do you get to continue to treat to "get all the abberant evil few" (to paraphrase HR) or do you have to stop the trial at 24 wks regardless?

[Andiamo1]

I have been undetectable since week 2.  I was randomized into the 48 week arm and I am now in week 40!!  My experience wit Telaprevir has been nothing short of incredible after so many times treating with the current SOC flavor since 1989.

So -- lab-rat -- go for the rollover!!  And, good luck to you.

merryBe: I just had the best investing week of my entire life!!  I shorted the financial and real estated indexes on a 2 to 1 ratio on the day of the last FED meeting.

Eric