Telaprevir or Boceprevir?

[Magnum]

Spent some time with my Gastro yesterday. As many of you are, I'm also waiting for the PI release. An interesting statement the Gastro made was that there has been a 50% drop-out of clinical trials due to the side effects when using the triple therapy with Telaprivir, but only a 10% drop-out with Boceprevir? He insists on my waiting for the later when it’s available...

Anybody?

Magnum

[virgocharm]

my 3 month eot is tues. keep your head up rock. i see neg. boc rocks.

[mikesimon]

right!

[Rockerforlife]

Im waiting for my 6 month post PCR from the Boceprevir RESPOND 2 TRIAL,should have them Jan 19-2009.Undetected at 3 month post and was a RVR at week 2 after taking BOC.Im stll nervous as hell.Seems like the 6 month PCR is the final hammer that bangs on the board to relieve the pressue.


Chinese proverb
"If I keep a green bough in my heart, then the singing bird will come".

[frijole]

Magnum, thanks for postiing this thread and thanks for everyone posting all the links.  I think this will remain a hot topic all throughout 2010 and I think the winner will be ..... the first one out, no matter what the side effects.  I think, until all the III trial data is out from both drugs, it is hard to compare.

I think (but don't know) that the skin effects of Telaprevir would be worse in those with sensitive skin. Even on SOC there were issues of pruritis and psoriasis.  Many of us got rashes with SOC.  For me, they were livable and directly related to sun exposure.  Therefore, I think my rash would be nominal.  On the other hand, I know how much anemia I had with Ribaviron alone and wonder if Procrit would keep it under control.  Seems like even with epogen my HGB remained borderline 10.

Still, I am ready for whichever comes first.  I still wonder about how the merger into Merck will impact the development and marketing of Boceprevir.  With Vertex putting out statements to the effect that they want to become a drug company - that is, market and sell Telaprevir, it seems that they have more incentive to push to the finish line first.

I don't post often - it all seems the same sometimes, just new faces.  But this is a big issue and I need to stay on top of it.  I hope to see Boceprevir v Telaprevir in the topic line a lot.

frijole

[nygirl7]

I thought that eventually they had tweaked the tele and that was what helped with the rash?  I remember when it first came out people had such an incredibly hard time with it but then I thought they had done something that helped to fix it? I know I read it but don't remember how many years ago it was now.

[banarep]

atavan - a drug used to stop the itch, was what i was given.  plus you had to just power through it.  the telaprevir was only for 12 weeks and the rash normally shows up around week 9 - 10.

[newleaf09]

Susan and banarep, thanks for describing the rash.  I keep up with PI info because I was in the latest bocep. trial.   I always saw rash listed as the number one dropout reason for tele. and thought it had to be phenomenal if it made people quit a trial.  'Vat of boiling water' look would make one quit all right.  How did they manage it in the Realize trial?

[banarep]

i got the rash, it was almost a deal breaker.  but on the realize trial (current one) they knew more about it, and were ready to deal with it.  it was bad, but the meds they gave me helped.  susan400 you are correct, it was pure hell.

[copyman]

my telaprevir rash was very manageable but not as bad as a few I have heard of in these forums. the study center I was at had no dropouts and no one had the severe rash. they were right on top of it at the first sign of a rash. sent me right to the derm as soon as I mentioned itching. turned out to be the regular derm stuff that you would get even with SOC drugs. I believe the rash is for real but the reward (SVR) outweighs the risk.

[susan400]

One cannot say that the rash is  'manageable' unless one has experienced the Telaprevir rash first hand.  For me, it was far from being 'manageable'.  It was one h*llious rash,  middle letter here being an 'e'.  I could not tolerate it, but continued on with hopes that I would be undetected by the required 4 wk check point.  My arms and chest looked as if I had immersed them into a vat of boiling water!!  The little of cortisone cream that they would permit me to use was basically worthless on it.  I'll take dealing with anemia anyday over repeating that rash.  Needless to say w/o the Riba, it was a big time-wasting inconvenience for me and now, thank-you very much, it's screwed me over for my potential at being accepted into any more clinical trials since they consider me a Telaprevir failure!

Susan400

[Rockerforlife]

The company reported for the first time that in a Phase II study, a 48-week boceprevir regimen achieved an unprecedented 75 percent sustained virologic response (SVR) rate at 24 weeks after the end of treatment (SVR 24) in patients who received 4 weeks of PEGINTRON(TM) (peginterferon alfa-2b) and REBETOL(R) (ribavirin, USP) prior to the addition of boceprevir (800 mg TID) (P/R lead-in). This represents a near doubling of the 38 percent SVR 24 rate for patients in the control group receiving 48-weeks of PEGINTRON and REBETOL alone (ITT).(1,2) In a 28-week boceprevir P/R lead-in regimen, the SVR 24 rate was 56 percent. Importantly, for patients who received the boceprevir P/R lead-in regimen and had rapid virologic response (RVR), defined as undetectable virus (HCV-RNA) in plasma after 4 weeks of boceprevir treatment, SVR was 94 percent in the 48 week regimen and 82 percent in the 28-week regimen. RVR has been shown to be a reliable predictor for achieving SVR. These final results are from the HCV SPRINT-1 study in 595 treatment-naive patients with chronic hepatitis C virus (HCV) genotype 1.



http://www.medicalnewstoday.com/articles/130622.php

[JennyPenny2009]

"He also mentioned that Boce has a 50% SVR rate for non-responders (as myself), while Tele is less. Keep in mind he is talking about non-responders, not naive. "
_____________________________________________________________________
I just came from a Vertex meeting last week where the trial data was explained once again. There is a 50% SVR rate for previous non-responders who had a two log drop at 12 weeks, in a previous treatment with SOC. There is a 30% SVR rate for previous null-responders and close to a 90% rate in previous relapsers.

As Willy pointed out, (I think it was Willy), you have to be very careful when looking at these studies. It is amazing how data can be tweaked to say what the companies want you to believe. They almiost never quote rates from the standpoint of intent to treat numbers.

[jacksonblue]

Hello magnam i treated with telaprivir in the proof 3 rollover i did not notice any measerable differance in side effects other then inconveniance of dosing 3 times a day .treated 24 weeks svr and i had relapsed in past from 72 weeks drop out rates i beleive not much higher then soc  

[Willy50]

Hey, I wonder that one difference is that when the doctor is expressing his view he is answering and characterizing his replies of *people with your histology*.  That might make some sense, at least more sense.  It's a totally different thing to say that than;

(what you wrote was)--------------------------------------------
"An interesting statement the Gastro made was that there has been a 50% drop-out of clinical trials due to the side effects when using the triple therapy with Telaprivir, but only a 10% drop-out with Boceprevir?"
-----------------------------------------------------------------------------

I'm saying that the 50% is in error to the best of my knowledge and that in the boceprevir trials rescue drugs were allowed and therefore it might not be an apples to apples comparison.

You should also be able to look at the 107 trial which Hector provided or the results of Prove 3 (past TX failure trial) as a source of what to expect for general results.  In your case where you have a meld score, advanced cirrhosis or other issues or scores known by your doctor (and not by us) there could be reasons that he would expect a greater chance for discontinuation.  That may be reasonable and sound, but wasn't originally expressed in the first post.

Do you think that could be the issue?

You asked for a response.  ; )  I'm not intending to diss the Dr.  I wonder if there may be some miscommunication.

best,
Willy

[Magnum]

I listen very carefully when a Gastro or Hepatologist speaks. I repeat, he said 50% drop-out rate for Tele and 10% for Boce. He also mentioned that Boce has a 50% SVR rate for non-responders (as myself), while Tele is less. Keep in mind he is talking about non-responders, not naive.

I now remain confused as to why a doctor would give me this information unless he is misinterpreting studies he read. I’ve been going to this doctor for 10 years and can’t believe he would spout nonsensical and erroneous theoretical results, if they are indeed theoretical as opposed to factual. Obviously, I’m not going to confront a doctor’s point of view or statements in front of him and dis him, but I now wonder why others here are so adamant regarding that what he said is so off the mark.

I will now present what the Gastro said to the Hepatologist Robert Gish and see what his take on all this is. Stay tuned...

Magnum

[desrt]

I agree with Grand Oak in regards the value of "press release publications" from the companies producing the drugs. Anything that includes the phrase "Investors may also be encouraged..." automatically gets taken with more than a grain of salt.
As we get closer and closer to the release date of the PIs, we're going to see more and more people making tx decisions based on the share price of stocks. To me, this doesn't seem like a good way to make a decision of this type.

[WriteItDown]

I would think that in your situation you might well want to decide which one based on your experiences in previous treatments, i.e. if you had a bad time with anemia choose the Telaprevir, and if you had trouble with your skin, do the Boceprevir. Of course if you had both or neither issues that doesn't help.

[Willy50]

Is it possible the doctor said "fifteen" and it sounded like fifty?
-W

[Willy50]

(Grand Oak wrote);
"As for percentages Willy questions, it all depends on how wants to view them!

One can easily say that 80% of those able to endure the trial attained SVR even if 50% of those initially enrolled dropped out. This is substantially different than claiming that 80% of those enrolled in trial attained SVR.  

It all depends on the qualifiers for the numbers being presented."
********************************************************************
I agree that one needs to be careful about interpreting articles and pharm pitches.  Even so, quite often the articles are based on presentations at conferences such as EASL or AASLD and do indeed contain the facts.

I also agree that one has to be careful in assuming that trial results will be the same as aggregate HCV population results.  Even so; they are still the best way of comparing the compounds in trials.  

Magnum is trying to compare based on what his Dr is representing.  I'm trying to make the case that he is either not correctly representing what the doctor is saying OR that what the DR is telling him is patently incorrect.  (I think this is what is actually going on)  ; )
(Even Prove 1 and 2 trials had nearly a 70% SVR rate- I don't follow how a 50% trial drop out rate could ALSO have a 70% SVR rate, but then I'm just a layman)

This is a natap article covering the BID versus TID dosing trial which Copyman linked an article to.  Within this link there is a line which says;

http://www.natap.org/2008/AASLD/AASLD_43.htm
(about 2/3rds of the page down)
----------------------------------------
"Treatment Discontinuations

The overall proportion of discontinuations of all drugs for any reason was 15% (Table 2)."
-------------------------------------

Strictly speaking...... I suppose that one *could* discontinue and restart, therefore not be a trial drop out.  I fail to understand how 50% could drop out and the trial still have a 80% (actually, one arm had a 85% SVR rate; 80% was the worst success rate).

I would also suggest that the Vertex trial, which has treated over 2000 dosings of TVR to trial participants does have very predictable responses in SVR rates, side effect profiles and discontinuation rates.  One thing that *does* seem to change is the constant improvement in the ability to successfully treat participants.  This BID vrs TID trial was still a phase 2 trial.  We may yet see improved results post approval, improved results when rescue drugs are permitted or when predosing is permitted.
(strictly speaking, this was a European trial and they generally have better results than Americans do perhaps due to diet, weight, IR issues and/or many other issues)

Anyone can read the natap link and draw their own conclusions.  I post merely to question whether Magnum is getting good info.  It doesn't appear to be accurate to me.

best,
Willy

[HectorSF]

Magnum - Below are the " Most Common Adverse Events" for Telaprevir and Boceprevir.

Telaprevir  "Prove 2" Phase 2 (Treatment Naive) - AE Summary: More Rash, more Pruritus, more Anemia.
Control group 7%
Tel/PegIFN/RBV 11-14%
Skin irritation the most common reason for discontinuation of treatment.
-----------------------------------------------------------------------------------------------------------------------
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Boceprevir - SPRINT-1 Phase 2

AE Summary:
Skin rash or pruritis (itching) occurred with similar frequency in the boceprevir and control groups.
The most common adverse events reported in the boceprevir arms were fatigue, anemia, nausea, and headache.
The rate of treatment discontinuation due to adverse events was 9%-19% in the boceprevir arms versus 8% in the standard therapy arm.

Phase 3 studies in treatment-naive hepatitis C patients (SPRINT-2) and people with prior treatment failure (RESPOND-2) -- both of which include the lead-in period for all boceprevir recipients -- are currently underway.
---------------------------------------------------------------------------------------------------------------------
Telaprevir Studies

Safety and Tolerability Across PROVE 3, Study 107 and PROVE 2

In Phase 2 clinical studies to date, more than 1,000 patients with genotype 1 HCV have received a telaprevir-containing combination regimen, and the adverse event profile is generally consistent across studies and prior analyses. In the PROVE 3, Study 107 and PROVE 2 telaprevir studies, the most common adverse events reported more frequently in patients receiving telaprevir were gastrointestinal events, skin events (rash, pruritus) and anemia. There have been reports of severe rashes in clinical studies of telaprevir-based therapy. Other adverse events reported were similar in type and frequency to those reported with peg-IFN and RBV treatment.

In the PROVE 3 interim analysis, 16% of patients in the telaprevir-based treatment arms discontinued due to adverse events prior to week 36, while 4% of patients in the 48-week control arm discontinued treatment in the same time period. Rash was the most common reason for discontinuation in 6% of patients. In the Study 107 interim analysis, 8% of patients discontinued due to adverse events. The most common reason for discontinuation was rash in 4% of patients. In the PROVE 2 final analysis, 14% of patients receiving a 24-week telaprevir-based treatment regimen discontinued all study drugs due to adverse events, compared to 7% in the 48-week control arm. The discontinuation of all treatment in the telaprevir-based treatment arms due to rash was 7%.

Best-
HectorSF

[GrandOak]

I would highly recommend reviewing the materials at Clinical Care Options (which is free to join) for Hepatitis.  The provide a lot of good materials presented at the liver conferences along with study material and published study results. In particular you may want to review the findings presented at AASLD or EASL over the last several years as well as those in the Hepatitis journal.

I've found that their materials, which is also used to assist in medical training, can give you a better understanding and base from which to have meaningful discussions with your doctor.

I try to not place a lot of stock in the press release publications from the very companies who are trying to produce the drugs, which obviously are going to spin findings in such a way as to put their drug in a favorable light.

I have found that many doctors do not go into in-depth discussions because they lack the time to be able to fully explain the information in a detail which assures that the patient fully understands what is being conveyed to them.  So, the better educated you are on the topics going in, the more meaningful your conversation can be coming out.

As for percentages Willy questions, it all depends on how wants to view them!

One can easily say that 80% of those able to endure the trial attained SVR even if 50% of those initially enrolled dropped out. This is substantially different than claiming that 80% of those enrolled in trial attained SVR.  

It all depends on the qualifiers for the numbers being presented.

Bottomline I've heard is that the risks do not outweigh the gains for these two drugs and that the SX, albeit sometimes severe, can be made more manageble with rescue meds.  But also that much like current TX meds, the SX for new meds being added to the mix is unpredictable.  In that respect, future TX will not be much different than current in that each case needs to be considered independently of one another and handled accordingly.

But, if one has attempted TX in the past and their SX to it are known, it may have bearing on which of the new meds might be used once thay are fully approved.

In the end, nothing currently has, or promises, 100% SVR so while new meds over an increased promise, they still are not the silver bullet for HCV.

[Willy50]

I thought that someone would reply to this....and they did with the info.

I would echo what Copyman and banarep posted.

If some member here posted that there was a 50% drop out rate in TVR trials they would get taken to the mat.  I wonder how your doctor would explain an 80% SVR rate when 50% drop out of the trials?

If the doctor is SO unknowlegable...... how much credence can you give them?  I would investigate the current trials and get the info either from the board, from natap coverage on EASL or AASLD.

My very brief summary of the differences is that the two compounds may produce comparable results but that TVR may be a smidge better w/ SVR rates.  It also produces a shorter TX time for more people.  I believe that the shorter TX time results in a lower drop out rate.  This can be offset by the rash issue but the issue has been improved in the rash management program.

To some extent, I don't think it is even fair to compare the two compounds since Boceprevir attained their SVR rates using rescue drugs and predosing of TX (a 4 week lead in prior to starting the PI).  

I would give the DR a little more credence if they had imparted this info to you.  

Maybe they know more...... but I can't tell it from what you write about what they tell you.  Why make a very important decision based on incorrect, old or incomplete information?

Of course.... maybe that describes what I provide, but I think that the Copyman link supports my view.

best,
Willy

[banarep]

Most recent info from the Boston meeting:  Boceprevir causes more anemia, Telaprevir causes more skin rash - both are treatable.  The study I am on with telap. does not allow resuce meds, but they do not seem to be as need as much as for those on boceprevir (for anemia).  But both look very promising, I think telaprevir will be out 6 monteh to a ayear sooner.

[Magnum]

As the link newleaf09 mentioned suggests, Boceprevir has less sides and that is most likely why the Gastro wants me on that instead of Telaprevir. He also mentioned that prolonged usage of Telaprevir as opposed to Boceprevir caused some to become more likely to experience suicidal tendencies. I certainly don't need that on top of the other sides.

I will gather more and more info before hopefully starting treatment the end of next year, if the FDA doesn't drag their feet and licenses the pharmaceutical companies. Otherwise, the debate is sure to rage on and on and on...

Magnum