Telaprevir, Boceprevir ... Should I TX?

[GreatBird]

Hi All,

It's been an eon since I asked a question here (at least a year--or maybe several), but this is how it stands. I just got the results back from the biopsy I had done last week. It shows absolutely no change (grade and stage wise) since the last biopsy I had in 2002, almost exactly six years ago. (I am a grade 1, stage 2). I have geno 1b. Usually a low-ish VL (under 1mil) and no symptoms (every time I think it's the hep it turns out to be something like menopause or Vit D deficiency or the like). I think I've been infected for almost 50 years (since I was six or seven).

As a TX naive patient, I have been asked to participate in the Boceprevir study. I am very interested in doing this because I have the time with relatively few commitments and the chances of clearance are finally good enough that it's very tempting. I'm also not getting any younger, and am currently insured (even though I got laid off from a job in July). (Not that I need insurance for the study, but it makes me feel more secure about the whole thing.)

So, one of my questions is: is there any advantage of Telaprevir over Boceprevir?

From the little information I've found, it sounds like Boceprevir has fewer sides and they both seem to be enough of a "magic pill" to make the SOC actually work (at least more of the time). My understanding of the Boceprevir trial is that of the three arms, if I end up on the non-PI arm and officially don't clear, at that point they would give me the PI.

I'm looking to the wise and knowledgeable folk on this board to let me know what they think. Should I? Shouldn't I? Is there an advantage to waiting any longer? I've always been adamant about waiting (a looong time ago I got into some rather rough words with folks on this board because my stance was so unpopular), and felt a definite advantage at not messing with my strain of HCV and immune system. So now it's somewhat weird to be standing at the starting line, and I'm a bit uncertain. Your thoughts and opinions, please.

[Magnum]

I would wait. I'm stage 3/4 and I'm waiting after my Hepatologist's assistant said that's what she would do because I've already put my body through 4 torturous failed treatments. My last 2 biopsies (3 years apart) showed very little progression. Although I'm considered at the start of Cirrhosis, it is not a death sentence by any means.

As for the two drugs you mentioned, although I'm not a doctor and my advice is strictly my opinion, I would wait until it's released to the public, for the simple reason that you may go through the torture of the two other mandatory drugs, and get a placebo instead of one of the “miracle” drugs you mentioned. Otherwise... it's up to you. Good luck...

Magnum

[willing]

Bill : congratulations on your 30 day - and on delaying the 90! I've always thought this window of time - when one is completely  'blinded' to the status of past/current hcv infection, is a unique/valuable opportunity to try to determine whether it has any impact on  QOL. In principle, if HCV status really has any bearing on how one feels, it should be possible to make a pretty good guess about the 24w-post test before ever seeing the results... Anyway - all the best on the outcome.

Re the bxs, I'm now less inclined to trust them as a gold standard and am instead putting more faith into  composite measures (what's the trend in platelets, INR, portal/spleen sizes, etc. etc.). Basically -  as things start going south evidence should surface..

Keith/All: whereas the costs of delaying tx are a relatively gradual deterioration (in liver and svr odds) the benefits of waiting come in quantum improvements. Opportunities like the current TV/BC trials open and close. Based on the information available for tx-naive, racking up another 3 years of damage while waiting for essentially  the same odds after approval does not seem a great move.

Jim: yes, the numbers are just shorthand - but unfortunately the text (and follow up conversations) confirmed  discrepancies, both in different samples and in different interpretations. ( The last pathologist was adamant that, even after consulting with a colleague, she just didn't see what the next-to last had seen). I'll try to gather the reports and post them, but, given the choice of readings, I think I like yours the best...

[Keith_2008]

It looks like a lot of people weighed in on this post with many different opinions. As far as treating with Boceprevir or Teleprevir they both seem to have a higher success rate than any other form of treatment I have seen. If standard care treatment (Peg interferon/ Ribavirin) has only a success rate of about 40% I could see why some people would not want to treat because your success rates are lower than 40% and the treatment is difficult and long. On the other hand if you had a success rate greater than 60% that is a whole lot different. I have seen some study's that suggest more like 75% range while on the Teleprevir or Boceprevir. It seems to me to be a no brainer as to what I should do. As far as taking the Teleprevir or the Boceprevir that could depend on a lot of factors like what's available in your area and whether or not you maybe willing to suffer more side effects in an effort to shorten the treatment time. I personally am doing the Boceprevir which has the least side effects out of the two. Knowing that these two trials have the best chance of success I don't know why someone would have a problem recommending these two trials. I also don't think you have to be a shareholder to recommend them. I personally don't know of any other trials that are having better success rates. I also believe that anyone who gets into one of these trials should consider themselves lucky considering how much these drugs cost and the fact that most people would not be able to afford them. The bottom line is that these two trials have the best chance of success which is what everyone wants. I hoping I can be successful my first time through treatment and not have the difficult situation of having to relapse and do treatment all over again. Good luck to all!
Keith

[Bill1954]

Perversely, solid evidence of stage 3 w/complete bridging would have at least made the decision for you. I’m impressed with the amount of diagnostics that went onto this, but I see what you mean; you now have a plethora of knowledge, and are really no closer to decision time based on data, anyway. This one might have to come from the heart or gut, rather than intellect.

How is your life right now in terms of timing? Do you have any windows of opportunity opening soon that might make a year’s Tx any less painful in terms of stress?

As usual, Jim makes some *very* good points for postponement; I haven’t had the opportunity to review any of the abstracts from the November meeting in SF; have you found anything from there that might warrant pushing treatment back for another year?

I dunno, Walt; you might have a chance to rewrite that White House episode; it might be better to use insecticide rather than let D. Duck destroy the whole structure. I wish there was a good answer for you, Willing; I really do.

My 30 day post TMA was RNA negative. The doc decided to nix the 90 day test; said I can wait for the six month, which is due middle of January. I see my PCP nest week; I might ask him to squeeze in enzymes, just for a preview… I was always a high-enzyme guy (~300/180) while RNA positive. This might yield a little info; but like you, I’m not quite sure what I’d do if it was positive :o).

Thanks for the update; it’s always good to hear from you—

Bill

[jmjm530]

I guess the point I buried was that your readings are probably not as far apart as at first glance. Certainly you're not stage 0 or 1 and it also appears you're far from cirrhosis. You're somewhere in the Middle Class, like many of us!

[jmjm530]

As you know, I went through a similar exercise -- four pathologists same slides. What I learned is that the language can be as important as the numbers since different pathologists will grade differently. But in a technical sense, unless the bridging is complete, it's stage 2 and not 3. Stage 2.5 (which one pathologist gave me) turned out to be stage 2 when pressed because technically you must stage in whole numbers. The pathologist who gave me a 2.5 took a half hour with me to explain how my staging was done and actually let me look into the microscope. He was quite adamant that my previous stage 3 was incorrect as the bridging was not complete enough. Given all they took from you, my guess is that the little liver you have left is probably a solid 2 for the most part. So now you have four readings :)

-- Jim

[jmjm530]

Will: To delay tx without good cause, after say 50 or so, seems unwise.
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We are much in  general agreement -- although "age 50" could be debated. The disagreement is what is "good cause". Which leads to the reverse your statement which is equally true --  "To treat without good cause, after say --- or so, seems unwise".

We are in a unique point in time where " new drugs should be out in a couple of years" is no longer wishful thinking but the most probably outcome of trials and the subsequent FDA approval process. Waiting a year or so, as not to age ten --  with often the accompanying "outing" of latent autoimmune conditions --  is certainly something for anyone in the treatment decision making process to think about.

[willing]

yeah - I still have scars from the holes (and a lot of blood-stained t-shirts). The whole exercise made me deeply suspicious of the accuracy of staging. The surgeon got plenty of tissue, separate cores from each lobe, and some nice glossy pictures.

Then the pathology reports... I got 3 readings one from a world-class hepatologist, the other from transplant centers at Stanford and Pittsburgh (wanted to make sure). Two of the three agreed with each other and with the previous, standard percutaneous bx (some areas 1 some 2). The third, on the same slides, saw evidence of much more advanced progression with bridging - which would be much more consistent with the fibroscan results.

So go figure... at this point I've run out of experts; and am not really inclined to keep taking out more chunks just to see what stage I'm at (reminds me of that cartoon where Donald Duck destroys the house while chasing a mosquito). The experience has made me more philosophical about what it means to know something..

So when do those 12w test results come in ?

[Bill1954]

Sorry to interrupt this joint dissertation in philosophy, but I was wondering how the laparoscopic Bx results turned out; last we talked, you were still shaking the anesthetic out of your noggin.  And other than that—how are you?

Bill

[willing]

>my life and health (outside my liver) is not better since treatment

from the perspective of one still dealing with hcv infection that parenthesized qualification is an important one. H**, we're all dying, and can fully expect each day to get progressively worse - but there's no sense rushing things. To delay tx without good cause, after say 50 or so, seems unwise. The prevailing view of fibrosis progression, as I understand it, is not linear. Past a certain point it picks up sharply  with age and fibrosis level eg
http://www.ncbi.nlm.nih.gov/pubmed/14960533



The tx-related 10X aging is also something I experienced, and am not looking forward to, but the alternative looks worse.

stay well.

[jmjm530]

"a year or so" may be as long as three years for the drugs to come to market (not currently following the scheduling)  but the point is the same and we will certainly know more in a year than we do now.

[jmjm530]

Willing: Willing: However with respect to waiting, you really have to ask yourself what you're waiting for
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One last point. If one does make a decision as stage 2 to treat in the near future, then one reason to wait at least for a year or so is to wait for current trial data to mature and for the drugs to come to market. At that point one can not only make a more informed decision about which PI mix to jump into but also partake in individualized treatment including helper drugs, more frequent viral load testing as well as addittives such as Alinia, Statins, and whatever else looks promising at the time.

[jmjm530]

Just to summarize in a personal sense, my life and health (outside my liver) is not better since treatment. To the contrary. Treatment lost me two years of work and friends and aged me ten years. Nothing was better afterward. Yes, I felt I made the right decision because I was told between stage 3 and stage 4. But if I was told I was stage 2, no way would I have treated then. And knowing what I do now, no no way would I treat as a stage 2 to do it all over again. But of course, YMMV.

[jmjm530]

Willing: However with respect to waiting, you really have to ask yourself what you're waiting for
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First, as you stated, one might wait for both better odds and/or shorter treatment duration.

But the other thing is that "watch and wait" doesn't mean necessarily waiting for any particular treatment. In short, one might simply wait to wait, or another way of saying is that one waits because one prefers not treating to treating.

Assuming that the HCV isn't impacting one's health outside the liver, and assuming the liver is being monitored and no progression is noted -- it's very reasonable to simply wait until one reaches a point where treatment might be indicated either because of health factors or liver damage.

In other words not treating is a decision in and of itself to be compared against treating which has its inherent risks. So at the point one decides to treat, then jump in with the best treatment available.

That is in fact what I and many other "waiters" did. I wasn't waiting for Telaprevir or Boceprevir (they didn't exist) -- I waited for many years because I felt the risk of treating outweighed the risks of not treating.

In very, very short -- for some treatment may never be necessary -- and could reasonably withheld  until even a more gentle and more effective treatment comes along.

[willing]

no doubt that r7128 is one of the more promising stat-c candidates - and congratulations on getting into the study and on your RVR. However, as far as  I know, there are not yet any large scale studies recruiting  for it -  in fact Roche/Pharmaset seem to be dragging their heels in that regard (perhaps you as have some insight as to why, particularly now that r1626 trials are not likely?)

However with respect to waiting, you really have to ask yourself what you're waiting for ("Good things might come to those who wait; Not to those who wait too late "). For someone with GB's profile, the odds from BC (lead in + 48)  appear to be around 80% and are likely to be at least that for TV/48 based on the prove 2 data.  Reasons to wait might be even better odds or shorter - say 24w tx but both of those are far from certain. For example, assuming a generous 90% SVR rate amon the R7128 RVRs still gets you back to the same 80%. Meanwhile the clock keeps ticking , with accompanying fibrosis progression and decreasing SVR odds.

[DragonSlayer45]

I agree with Jim, he is usually right on with  his advice.

With no change in 6 years you may have to to wait to see how the other drugs shake out. I am in a early trial of the polymerase inhibitor R7128. I cleared by week 4 (VL 8 million to UND) and I was still clear at week 24.

The early data showed 88% of geno 1's (naive) cleared at week 4, and 90% of geno 2 and 3 non-responders. It has shown no evidence of viral mutation and had no adverse sides. Unfortunately you still have to take it with peg and riba and get all those sides. It is still early and SVR data is not back. I imagine in 6-9 months that data willbe in for the early arms.

My guess is future trials will shorten the duration of the peg/ riba part to 24 weeks from 48, but that is just a guess. It is not based on anything I have heard. It would be nice if they can lose that part altogether.

Ultimately this is a personal choice and one you have to weigh for yourself. If you are not comfortable wait, if you are comfortable with what is going on then treat. They are making great progress with these new drugs. Just remember that they are still using them with Peg and Riba. Those drugs are not a picnic.

Here is study if you want to read what I referred to on R7128:

http://www.natap.org/2008/AASLD/AASLD_22.htm

[willing]

cando - hope you had a  good thanksgiving - and best of luck going forward

GB - yeah, brave new world indeed; think of the level of confusion around here once there's  a dozen different options to mix and match...

As far as tx vs bc - my sense is you're making a good choice. . Telaprevir has yet to report anything that tops boceprevir's 74% svr12 from sprint II (and since that's ITT you can expect better odds if you follow though with tx).  However, Schering's current edge is likely to be short-lived  : Vertex's prove II reported  69% on patients in the T12/PR24 arm and once their 48W data comes in they'll presumably at least match Schering.

[jmjm530]

With no progression in six years you have time to wait for the drugs to come out of trial.

You will then have both more information on comparative results as well as more latitude which would make treatment more individualized with the right liver specialist.

Watch and Wait requires patience as these drugs come down to the finish line but they're almost there.

As to which is better now, I'd do a lot more independent research but if I had to choose now  it would be Telaprevir hands down. They have the head start and just look at all the folks here like Andiamo who already SVR'd with Telaprevir. Seems like Bocaprevir is just getting going.

Docs offer you whatever trials they have slots to fill and not necessarily what's best for you.

Be well,

Jim

[fretboard]

Yes I'm in a BOC trial, I was excluded from a telaprevir trial back at the beginning of the year.  I always took that as a blessing as I feel very comfortable being in the study that I'm in, I only been in for 2 shots worth, so I just started.  I'm glad to hear that you have educated yourself on HepC and the various tx plans and trials going forward.  I have insurance as well, I didn't choose a trial to have someone pay for it as much as I like the personal care and monitoring that they do.  Early on I was seeing a GI under my insurance and he was just an idiot.  I met his NP and I asked her a few questions, she was nice enough, but her attitude toward me was very indifferent.  At that point I realized, that I was just gonna get my meds from them and that would be it.  There are alot of doctors and healthcare professionals who still look down on us heppers, that's how the GI and my HMO was.  I was glad that I went back to the clinical trial site and found me an opening.   good luck  

[GreatBird]

Gator--oh best of luck with the final results. I'm rooting for you. And thanks for sharing your experiences.

willing--yes. i am willing to take the plunge. finally. and truly. ;) thanks for letting me know what is coming down the pipeline. i have had my eyes on VX950 (and the like) for quite some time. it's exciting to see there are more developments. it also seems that they are FINALLY thinking to tailor the tx to at least some variables with each patient instead of treating everyone with the same genotype the same. can you imagine how amazing it will be when they are able to really take an individual's genetic makeup and medical history into account when they devise a cure cocktail?

[can-do-man]

No problem here my friend, heck i disagree with myself alot.:) I know one thing we will both agree on and that is we want everybody rid of this c.r.a.p. God bless and happy thanksgiving to you and yours.

Willing good to see you here, and thanks for all yours and frijoles help.

[willing]

well, well, finally taking the plunge..sounds like ayou've got a sound plan - with your profile I assume you're looking at odds in the high 70s or better with either of the ns3a PIs. Because of the different dosing regimes used in the Phase II trials it's hard to make a direct comparison  but my impression is that the results are quite close. The Phase III data will make comparison easier, but given the similar underlying mechanism of the PIs and similar escape mutation profile, surprises seem unlikely.  As best I can tell, the schedule for departing buses for SVR looks like (1) the ns3s phase III trials leaving now, (2) the phase II/III for r7128 trial 900518 and other gen II drugs over the next two years (3) tx post-TV/BC approval around 2011 and (4)  combined ns3/ns5b PI trials starting ?

I'm in worse shape but still stalling because as a relapser I think I'll need better odds - probably bus 3 so I can at least add alinia, statins  and anything else that crops up between now and then.

[Fl_Gator]

The following is what I have experienced so far...

I am in a Vertex trial...just finishing week #24. I didn't get the "rash". I learned that only 9% of patients get the "rash". I did itch a bit but found relief in a nice shea butter cream. I have fatigue and brain fog but most days weren't too bad. I developed some anxiety and appathy around week 10-11 and went on AD's. I did feel better after week 12 but it's hard to say why. I got more sleep as I didn't have to stay up late to take meds after week 12, I went on the AD's and went off the tripple therapy which could have been Telaprevir. My HGB dropped around week 5 or 6 and I took a riba reduction but no rescue drugs. I am still winded but my HGB is on the rise.

In six months I hope to report SVR. I wish you the best in what ever you decide to do.

Gator

[GreatBird]

Trust  me. I know it's going to be very difficult. That's one of the reasons I've waited. I'm willing to do the difficult, though, *if* it's going to work. I've been reading hepC boards on and off for six years, so I've seen the highs and lows of it. I'm not so sure that knowing what I do is good, because sometimes it's better not to anticipate. Still, knowing the potential potholes on the road will help me not to freak out when I hit one.

Are you on one of the clinical trials?