Telaprevir - 18 yes 0 no

Whew - that was dicey.  One of the FDA advisory committee panelists was agressive in his pursuit of issues with the rash, but in the long run, he and everyone else on the panel voted to approve.

Now it goes to the FDA.  Approval date (or not) is May 23. Some people are betting that the FDA will announce both BOC and TEL on May 7 - the date for Boceprevir approval (or not)

[frijole]

The biggest issue on the table was the rash.  DRESS (drug rash with eosinophilia and systemic symptoms) and SJS (Stevens Johnsons sydrome) were the biggest issues.   Although both of these can be very bad - the SJS can be life threatening - in the long run the panel decided the benefits outweigh the risks. They didn't recommend additional trials.  Vertex did an excellent job of presenting and were very well prepared.  

[HectorSF]

Good news!


Hectorsf

[frijole]

Question 3 ---Please comment on the strength of evidence to support response-guided therapy with telaprevir in combination with pegylated interferon and ribavirin for the following patient groups?
a)Treatment-naïve
b)Prior relapsers


seems like panel is leaning towards RGT for relapsers

chair summarizing - -ringing endorsement for RGT in treatment naives. less clear for strong endorsement for relapsers but majority say evdience supports RGT in these patients. some concerns for underlying conditions...

[frijole]

4. Please comment on the strength of evidence to support a recommendation for use in specific populations, including but not limited to Blacks/African Americans and patients with cirrhosis. What, if any, additional efficacy or safety data are needed for specific populations

clay - patients with gout and tuberculosis
clay - i know, i'm driving people crazy with this tuberculosis issue...
chair summarizing question 4 -- need more data on patients with gout, TB... (clay!) more data on AAs and cirrhotics, some concerns about null responding cirrhotics, patients over 65

[nygirl7]

My mother had SJS - you dont ever want to see anybody who gets that.  She was in the burn unit of our major hospital out here for months......

Sounds like they had more trouble getting through then boce I would have thought it would have been the other way around.

Exciting times ahead - very exciting indeed.

Thank you for the excellent recaps Frijole I wouldn't have known where to look to watch.

[frijole]

Good news for sure.

It looks like Telaprevir may be on label for null responders.  Probably not so for Boceprevir because they avoided them in their trials and did not have the data.  They had a little data from the placebo group who did not respond and were then given BOC - I think about 30% were SVR - but the FDA advisory panel would not accept that data since it wasn't part of the trial.

The other really good news is that relapsers will be treated like treatment naive as far as response guided therapy.  That is even relapsers have a chance of 24 week therapy if they are EVR.

[frijole]

You are right, Deb.  I googled picutres of SJS.  All we ever heard it called was "the rash" and severe, yes, but I really never concerned myself that it might be life threatening.  We will have to be on guard with that one.
frijole

[Magnum]

Why isn't anyone talking about Boceprevir except for frijole? My Gastro wants me on it because I didn't have an issue with Anemia. Now I'm getting a feeling that Teleprevir is outgunning the efficacy of Boceprevir? Can anyone unconfuse me?

Mag

[susan400]

ALL, I have been talking about it wanting to get on the Bocep.  I have not even had Telap. on my radar screen since I won't even consider ever doing it again.  However, each person has to make their own decision.  I had my experience with the Telap., had the horrendous rash 2 wks into it and I will not go through that again, have no desire to.  If given the opportunity, I'll take my chances with the anemia.  I went through all of my treatments anemic and only used the Procrit on 1 of the 10 TX's, I did.  

Susan400

[Magnum]

Unless my gastro changes plans, that's what I'm going to do as well. Luckily, throughout four tries, no Anemia. Still felt shi**y though...

Magnum

[miked]

About week 4 of my participation in the Prove 3 trial I got the rash from hell.

My family was camping at the lake and we had a great day at the beach.  At dinner that night my daughter exclaimed, "Dad, is that poison ivy all over your arms!".  

Well the poison ivy was actually the Vertex rash.  Over the next few days it moved around my body with the exception of my face (odd).

My doc prescribed a steroid cream and within a couple of days the rash was under control.

I went on to complete the 24 week Prove 3 trial and learned that I was UND between week 1-2 and remain that way to today.

Poor Susan400 above was also in the trial but didn't get inn the arm with RBV which I believe was necessary for RBV.

I'm so happy that these options are becoming available to everyone!!

miked

[frijole]

I think it is important for both drugs to be approved.  You and I and Susan and others here have had months - no, years - to weigh the odds for ourselves. I think if any one has auto immune problems (of any kind)  they ought to really look hard at this issue of rash.  It is some kind of immuno suppression issue and needs to be a primary consideration in determining which to treat with.  I have never had any skin issues or auto immune problems and think TEL is the right one for me.  Another thing --, I was following the investor blog.  I tried once to get on the FDA sight but it was jammed -- the message said too many viewers (imagine that!) -- so I missed a lot of details on a lot of stuff.  But there is some real issue with anyone who has gout or TB.  I think it is some kind of acid, but I can't tell you what.  I think there may be some label warnings about that.  I am sure we will hear more.

One other thing I didn't like about the TEL.  If anemia arises (and the anemia with TEL is greater than SOC, just not as bad as BOC) that the recommended solution is riba reduction.  Now I believe this can still be remedied with epogen, but that too will be off label.  I think it will be easier to get epogen with BOC.

I have seen such wonderful successes with BOC that that my mind is not set in stone.  I had anemia on SOC but it was not so bad that I would not consider BOC.  After cando man was cleared on BOC after 96 unsuccessful months on SOC, I was sold on BOC.  And Ejoili - and others i consder friends.

I am rambling.  Sorry
frijole

Magnum - you weren't a null responder were you?  YOu were a responder/relapser like me, right?  If you were a null responder you may have to find a good heppo - not a GI - to treat with.  BOC may be off label for null responders.

[Magnum]

I responded down from 3.2 million to 6500 with Infergen, but nearly died because it made me jaundiced. The other three treatments didn't work and I was stopped after several months on each, with the longest one going for 6 months.

As for Hepatologist, Dr. Robert Gish is soon opening a clinic in Las Vegas. I will run all this by him and post his response. He only does livers... Gastros do all abdominal cavity organs. Big difference if logic prevails. Stay tuned...

Mag

[susan400]

Who knows, maybe, just maybe, Merck will do a late stage trial, 'wide-spread' like throughout regular physicians offices, for the non-responders?  Stranger things have happened.   Merck, are you listening??????       The very first time I ever treated back in 1997 was in a Dr.'s office, a clinical trial, widespread, for the Ribavirin...back then, it was the 'new combo' and it was 3 x a week using the Intron-A and the trial drug "Riba".  But, that was a trial - widespread - late stage - in a regular doctor's office.  

Susan400

[JRenquist]

If boceprevir is off-label for non-responders, does that mean that insurance companies won't pay for it?  

My gastro really wants me to use that instead of telaprevir. I'd been looking forward to the telaprevir for a long time. Says that it's easier to treat the anemia than the rash and I had bad riba rash and autoimmune thyroid problems .

Said that Vertex had covered up the number of people who had dropped out of the original trial because of the rash, so he didn't trust them.  

Talked about mutation problems, but reading this forum, it seems like that's an issue with both of the new drugs.

Guess I'll just have to go  with whatever my insurance will pay for.  Does anyone have any idea how long it might take for insurance companies to put either PI on their formularies after FDA approval?

Thanks.  You guys are such a help.  Just reading this every day and knowing that I'm not alone in this is so helpful.  Wish I had more to contribute.  S.

[desrt]

If your doctor is thoughtful enough to take autoimmune, thyroid, and rash into consideration when Rxing, I'd listen to him.
Don't worry about 'contributing'. Learning there's at least one MD who feels Vertex wasn't honest in reporting their trial results just made my day more interesting.
Wish I could help you with your insurance questions, but I think we'll all just have to wait and see.

[Andiamo1]

"Says that it's easier to treat the anemia than the rash and I had bad riba rash and autoimmune thyroid problems ."

Does that mean he thinks that epo is safer than steroidal creams?  I would find another doctor.  Epo has many dangerous side effects.

"Said that Vertex had covered up the number of people who had dropped out of the original trial because of the rash, so he didn't trust them."

Does anyone think they could have gotten through all the people at the FDA looking at the trials if they were dishonest?  People talk about big pharma -- well Vertex is small pharma and Merck is big pharma.

Of course, I might be an ambassador and therefor must be dishonest myself.

I find these discussions, Telaprevir vs Boceprevir, about as rational as Republicans vs Democrats

why not poll all the people on this forum that took Telaprevir and find out who had a bad rash that wasn't' easily treated;  ask how many dropped out because of the rash.

[willing]

>If boceprevir is off-label for non-responders, does that mean that insurance companies won't pay for it?  
good question, I've been  trying to understand this as well. As far as I can tell under federal ERISA law that governs employer contribution health plans inscos can refuse to cover off-label rx use but individual state statutes can broaden coverage. For example California Health and Safety Code Section 1367.21 seems to limit off-label denials under conditions relevant to hcv use:
http://law.onecle.com/california/health/1367.21.html

>easier to treat the anemia than the rash
another great question and one many here seem to be wondering about.  The choice of sx is likely the biggest factor in the PI decision and It's hard to know who to trust. On one hand there's a lot of money to be made on the choice so the drugco marketing is suspect. Also there are very few Drs with significant experience at this point so their judgment is  mostly opinion.

My tendency has been to trust my fellow lab rats . Collectively there's' a lot of experience with epo on this forum. Nobody likes it, it's expensive, comes with risks and sx, but by and large it seems to work. This is what he may mean by 'easier'. The tela rash is more of an unknown. For some it was well-managed with creams for others (susan400/dointime/mremeet?) it seems to have been a show stopper. My current choice is to start with tela and switch to boce if the rash is too much. Direct feedback from other patients is probably  your best guide. However, if you really are a null-responder treating now may not be the best choice, regardless of sx.

As to "trusting" the drug cos that seems a non issue: they're in this to make money. One should expect them to promote their strengths and hide their weaknesses - it's part of the landscape. Vertex is smaller and more motivated and seems to have done more aggressive 'data fishing' than Merck, but any results that survived the recent intense FDA screening should be reliable.

[Andiamo1]

Susan400 dropped out because she was in the arm with no Riba and didn't respond.

mremeet was the only one that had the severe rash and had to stop but still ended up SVR

Dointime also ended up the the no riba arm.

I know about 10 people that participated in the vertex trials.  Only mremeet had the severe rash and all are SVR.  The rest had rashes that were slightly worse than a Riba rash, but all treatable with steroidal cream.

Personally, I would rather not take EPO unless I had  no choice.  Many doctors think it is linked to increase probability of cancer and until that is proven one way or another, I am  not taking a chance.

[susan400]

While the trial dropped me, at week 5 after my week 4 blood work showed that I had not cleared..., the rash appeared on me as a horrendous thing at week 2.  I never had rash issues anywhere close to being like the Telaprevir rash.  I was barely even noticing any rashes from Riba.  However, Telaprevir rash was like I was hit with scalding hot water.  I had horrible hive-like, blistery like things on my body.  The steroidal cream was little to no help with this rash.  In fact, the steroidal cream was OTC and it made me sweat, which in turn made the rash itch more and made the breakout repeat.  It's not something I will EVER consider going through again.  I'd rather keep the Hep C, not be SVR than to have to go through that horrible thing again.  But, that's my choice.  Susan400

[Magnum]

In the context of our discussions of rash vs. anemia, anemia can be controlled. Rash? When both drugs are approved, it would not be regulated as to when and if to change horses (drugs) mid stream. It's not a dictatorial mandate by the clinical trial directors at that point.

So, my summation on all this is that if one doesn't work, try the other, but why suffer to start with the proven rash horror stories. Some would rather dive off the empire state building or climb to the top of Mt. Everest naked than to go through the rash. Torture should never be part of a treatment...

Magnum

[pilgrim1951]

Just a quick response to all of this rash and anemia dialogue.  I was in the phase III Vertex trial and had a terrible rash that convinced my doc ( great guy at UPenn) that I "probably" was on teleaprivir.  My blood counts were so bad I almost reached the point of needing a transfusion (the trial didn't allow Procrit).  Turns out I was in the placebo arm of the trial and did not get these side effects from telaprivir.  So, I guess that some people suffer these sides from the existing protocal for treatment.  Food for thought.  SVR is gret regardless of how you get there.  

[Isobella]

First of all..big hello to Pilgrim, one of my fav lab rats!!

I remember you thought you were on tela because of the rash and then I got a wake up call at 24 weeks when they extended me to 48 and I then thought I got the placebo. What a trip we had, my friend!  Hope you are doing well and enjoying your SVR.

To everyone else, I treated in a Vertex trial for a total of 48 weeks.  The first 12 were triple therapy.  I have a lifelong history of contact and atopic (eczema) dermatitis.

I didn't experience a rash from tela at all. I did, for a few weeks, experience what we here on the forum called the riba rash....random small red dots on my body.  Throughout the 48 weeks, I did experience the photosensitivity that riba can cause.  I spent most of my tx oceanfront, so I stayed inside or in the shade during the day. If I didn't my skin felt like liquid fire. That lasted 48 weeks, not just the 12 weeks on tela.

I don't understand why any treating center would not offer anything other than an OTC solution after seeing what sounds like a pretty severe rash.  Susan400 , my heart goes out to you.  If memory serves, when Mrmeet was in rash trouble, he was given steriods and perhaps other rx help.  And I believe there was another forum member that was a school teacher that experienced a severe rash as well.  Hopefully he is around and will give his insight.

The center that initially diagnosed me no longer gives Procrit when patients become anemic.  They prefer to dose reduce and tranfuse at Hgb < 8.  They believe the risk/benefit ratio is not worth the risk of aplastic anema.  The center that I treated at believes in Procrit...thinking hit the virus hard and keeping patients on full doses is best.  

The anemia we all experience is not like the aplastic anemia Procrit may cause in some patients.  The rash some of us may experience on tela will not come close to SJS.  Maybe we should look at the number of adverse reactions from Procrit vs the number of adverse reactions to the tela rash-SJS when deciding.  

I can only give my opinion based on my 12 week experience with tela.  But please understand, I don't take this lightly.  I passed this virus to my only child.  Every single day I toss this these factors in my head and keep coming up with what is for us the best answer--telaprevir. I would also want to be aggressive and add Procrit to the mix if need be.

Please don't demonize tela based on the rash issue.  Please look at the numbers for cure rates, adverse reactions, risk ratios for both the treatment and the rescue drugs that lead us to SVR.

[Andiamo1]

Finally a voice of reason in this discussion.   Thanks for adding some information to the discussion.

All you have to do is look at the total dropout numbers due to sx and you can see that both drugs have about the same number.  SJC is very rare and I think mremeet was the only one to have it.  A rash that is very treatable is the more common SX.

Procrit (epo) is a very powerful drug with major side effects and should not be taken lightly.  Anyone choosing between these drugs needs to understand that both have side effects that are manageable for most people and both have risks that can be serious.

[willing]

good posts but I can't see what has been 'unreasonable' about this discussion. Choice of sx is *the* major factor in the upcoming PI decision many are facing. This was the first question put to the advisory panel and is  also likely  the 1st question in the mind of many warehoused patients about to restart.  The more information we can share on the topic the better.

Frijole's decision to favor tela because of  bad anemia in past tx seems as reasonable as  Susan's refusal to face the rash again or JRenquist's Dr's recommendation that a history of bad rash problems in previous tx makes tela a poor choice. Acknowledging that tela is not the best choice for all patients hardly seems like demonizing it. From the data now available it seems at least half will be able to handle triple tx with no major complications, most of the remainder will require manageable intervention for anemia or rash and under 10% will hit more serious trouble,

Among  that minority of patients   there doesn't seem to be  any evidence to contradict JRenquist's Dr's judgment that the anemia is easier to treat.  The different tx outcomes for dointime, susan400 and mremeet indicate the rash is unrelated to viral impact. All three had a nightmare rash but susan400 and dointime  experienced breakthrough whereas mremeet got SVR. Another board member  who had promising viral response but  was knocked out by severe tela  rash, to the point of requiring hospitalization, was josiejo:

http://www.medhelp.org/posts/Hepatitis-C/VX-Rash-Victims---speak-up-please/show/291263?personal_page_id=295381#post_4907231

In all those  cases only stopping  tela provided resolution implying by definition that it could not be 'treated'. On the other hand I haven't seen posts/papers describing  an equivalent  extreme reaction to boce, so that Dr's call seems valid.

There was an interesting thread a while back that discussed correlation between light complexion/Nordic background and bad tela rash. It  may have been coincidence but identifying who is at most risk seems a big win. For boce, it's pretty obvious who should be staying away.

[can-do-man]

I just had a recent follow up with my hepatologist, he has been involved with both PI's sense the start of these trials, he's very excited about both drugs and seems to agree the main reason choosing one drug over the other boils down to the rash and anemia issues. He feels both are great drugs and pretty much equal when it comes to curing HCV.

Their phones are ringing off the hook with people waiting to start, he feels it could be late summer before they are ready to begin though  sooner the better. Folks read alot about tx, find a good doctor who has been invoved with both of these drugs and let the fun begin.

P.S. I sometimes get this vision of a few here dressed up as giant telaprevir capsules standing on a street corner handing out pamplets. :).......... Best to everyone winning this battle.

Cando did

[spectda]

"P.S. I sometimes get this vision of a few here dressed up as giant telaprevir capsules standing on a street corner handing out pamplets. :).........."

LMAO :)

A lot of even more effective drugs in the pipeline moving to phase 3 trials. Hopefully tela and boce will pave the way for faster approval of the next generation
-Dave

[Andiamo1]

The breakthrough examples you gave were caused by the arm of the Prove 3 trial that had no Ribaviron.  

spectda saying that anyone here is a Telaprevir marketer is nonsense.  The only thing I point out is that both drugs have side effects that can be bad, but very few people experience them.  Telaprevir appears to be slightly more potent and basing a decision on people on the forum saying they had a rash can be a mistake.  This is not a statistically significant number of people here to prove one way or another the probability of any one person experiencing a rash.

Most people get a Riba rash, specially if they get some sun. Some people will get a Telaprevir rash and most in that group will get a rash that can be treated with steroidal cream.  Susan400 treated with an over the counter cream, so we can't say she couldn't be treated and had to stop Telaprevir.  She stopped because she had a breakthrough due to the lack of Riba.

Both drugs are significant improvement over SOC and both can have serious side effects.  Most will not experience serious side effects from either drug.  Treating anemia with epo can have very serious side effects.  These are facts, not opinions.  I question a doctor saying that anemia is more easily treated than a rash, when the treatment for anemia uses epo.

The Telaprevir rash seems to be caused by a complicated immune system response.  I developed psoriasis from Interferon in a prior treatment, but had no Telaprevir rash, for example.  So how do you predict the probability of anemia or a rash?

I was developing fibrosis at a rapid rate and that is why I chose to treat aggressively.  Many of the drugs in trials now will likely be more potent and might have fewer side effects.  The decision to treat now or wait is a complex and personal decision that should be based on the likely probability of outcome for each choice.

[spectda]

"spectda saying that anyone here is a Telaprevir marketer is nonsense."

I think you need to reread the posts. I didn't say anything like that.

At the same time there does seem to be some grandstanding going on and I am not sure why.  Perhaps some of it has do with financial investments or an association with a pharma company, hopefully not.

I am thankful for boce which hopefully will have defeated my virus, but I believe that our loyalty should be to our fellow hcv suffers rather then a particular drug or pharma company.

I wouldn't defend the rash of tela or the anemia of boce and I wouldn't be promoting one over the other without understanding an individuals personal situation. We are lucky that these new drugs will be available to hcv sufferers, but the fact remains that the choice of tx largely comes down to side effects as has been stated over and over.

Approval of tela and boce will be a huge win for our community after all of these years of waiting. They will allow an enormous amount of people to svr in the coming years while even more effective drugs are developed with hopefully less toxicity.
-Dave

[frijole]

Excellent discussion and one I hope to see expanded in the following months.  I believe Cando man has hit on a critical point. We have only so much authority with our physicians.  We need to choose the most knowledgeable hepatologists who have kept on top of the trials.  I know the GI I treated with in my town of 100,000 will not be informed.  I know that there are a lot of GIs who hate treating C patients (they really don't make money on us) and prefer to run as many colonscopies thru their practices as possible.  Those physicians who have kept on top of the trials are also the ones likely to see us as informed patients who might have a say in treatment protocol.  If the hepatologist I confer with refuses to merely consult on treatment with my local GI then I will treat in Big D.  (Maybe get to see a few Rangers games in the process).


friijole

[Andiamo1]

"P.S. I sometimes get this vision of a few here dressed up as giant telaprevir capsules standing on a street corner handing out pamplets. :).........."   sorry if I misunderstood this.  It sounds like marketing to me.

Not sure what you mean by financial links or association with Vertex.  I certainly have neither at this time.

I am thankful that Vertex developed Telaprevir and pioneered the research used by the rest of the companies, but that's it.  I do feel that people are not weighing the two drugs impartially, so I defended Telaprevir so people could make a rational decision between them.  People are blowing the common rash out of proportion.  The SJC rash is very serious, but very rare.  Nevertheless, all options have to be considered.

I had the opportunity to meet the CEO of Vertex and some of the scientists.  I was very impressed with them and found them not at all the way they are being portrayed here.

Some on this forum have been anti Telaprevir since the trials started.  People on the forum told me that I wouldn't reach SVR with it, that an SVR from a PI would not be durable.... I can't tell you how irrational some of the posts were in response to my posting that I started the trial.

"Perhaps some of it has do with financial investments or an association with a pharma company, hopefully not."

I would appreciate it if you would stop insinuating that anyone that thinks Telaprevir is a good drug must have some hidden agenda.

[spectda]

"P.S. I sometimes get this vision of a few here dressed up as giant telaprevir capsules standing on a street corner handing out pamplets. :).........."   sorry if I misunderstood this.  It sounds like marketing to me.

If you read all the posts on this thread you would see that I only quoted and laughed at that statement, I did not write it.


"I would appreciate it if you would stop insinuating that anyone that thinks Telaprevir is a good drug must have some hidden agenda."

Again I don't know where I insinuated that anyone who thinks telaprevir is a good drug has a hidden agenda. I am thankful for telaprevir and boceprevir and glad you are svr.

Please don't misinterpret my words. I am not the enemy.

-Dave

[Andiamo1]

Sorry for the misunderstanding.

[willbb]

Approval of tela and boce will be a huge win for our community after all of these years of waiting. They will allow an enormous amount of people to svr in the coming years while even more effective drugs are developed with hopefully less toxicity.

The above is a comment made by Specta  above.....to me this was a very intelligent  unbiased comment on this thread.



"I would appreciate it if you would stop insinuating that anyone that thinks Telaprevir is a good drug must have some hidden agenda." ..    ... who did this??

[Trish77]

I'm confused.  We have two PI's that are a hair away from being approved and increasing options and cure rates for people with HCV.  Each PI has different side effects associated with them that will allow people to choose which of the two is best for their own personal health profile based on past experiences with treatment side effects and simply based upon what they and their doctor deem best for them.  

This should be cause for celebration. Two very effective PI's becoming available that give naive and non and null responders and relapsers alike more hope for a cure AND some options for one or the other based on their personal health profile and preferences.  (Regulations, insurance companies, cost and availability aside....sigh.)

If a doc and a patient decide that Boceprevir is their best choice...great!  If a doc and a patient decide that Telaprevir is their best choice....great!  As long as they understand the issues as well as can be expected with new drugs and available information....all good.  Heck, there's even been discussions about how to effectively switch from one to the other if the main side effect of concern for each becomes a reality during treatment that threatens adherence / results.  Both offer more hope than people with HCV have had for awhile.

So...why does this thread suddenly seem like a contest of one over the other???  

*Slap* - sound of hand hitting forehead.  Geez.

[willbb]

If a doc and a patient decide that Boceprevir is their best choice...great!  If a doc and a patient decide that Telaprevir is their best choice....great!  As long as they understand the issues as well as can be expected with new drugs and available information....all good.

  Exactly.

[Andiamo1]

Yes exactly and that was my argument from the beginning.  Both are good drugs each with their problems; a rational approach is needed to decide which one is best for you.  The rash problems were overblown in my view and needed to be brought back to the point that people could rationally decide which drug is best for them.

"At the same time there does seem to be some grandstanding going on and I am not sure why.  Perhaps some of it has do with financial investments or an association with a pharma company, hopefully not. " --  this quote made me angry.  Perhaps I misinterpreted it, I hope I did.

[willbb]

  I can"t speak for what Specta meant by that..he can certainly speak for himself....I guess as someone waiting to treat with perhaps one of these.drugs..the only thing I am interested in is the data from Pharma(and saying that ,I always look at that with some trepidation)and the posts with  true experiences of those that have used these meds in trials ..sides and efficacy .

Then as a previous poster just said ..we can make up our minds with the advice from our docs.

I hope this doesn"t turn into a competition and arguments about what we should use and not use every time someone makes a decision.. just my 1 cent

Will





  

  

[Andiamo1]

I agree with what you said.  

[Andiamo1]

I am sure I never said that anyone should use one drug over another.  That is a very individual decision and both drugs are far superior to SOC.  I disagree with statements that say a rash is more difficult to treat than anemia and I would hate for someone to make a decision on that criteria.  I think I have the right to say that without anyone insinuating that I have some relationship to Vertex other than gratitude for taking the risk they did by developing Telaprevir.

My only points are as follows:

Most rashes are riba rashes or a Telaprevir rash that is treatable.

SJC is a very serious condition that is expressed as a rash.  It is close to impossible at this point to determine the probability of any individual getting SJC.

Anemia is not easy to treat. The choices are dose reducing or EPO.  Both choices are bad options.  There are serious side effects caused by EPO even if nobody on the forum experienced them.

[willing]

Andiamo: dointime and susan400 are the ones to comment on this  but from their posts my impression is that rash made  continuing tx impossible, regardless of viral breakthrough (the two effects are unrelated). So considering posts on this forum it seems we have at least four cases   where nothing brought rash under control other than stopping tela - and as far I know equivalent examples for boce are not available.

The point that treatment of the rash may have been inadequate seems valid - this is over 4 years ago and presumably more experience has built up. Also agreed that the PI-triggered rash and anemia happen against an existing  background of soc-triggered rash and anemia. Oh joy!

Haven't read much about carcinogenity of epo. However it seems significant that this issue was not raised by either FDA staff or the advisory panel members during the boce review. From Fuerstein's blog (it would be nice if full hearing transcripts were available) there seem to be various comments indicating FDA staff thought boce anemia was sporadic and well managed with epo though epo remains off label for hcv. Also relevant that the package insert for rbv flags it as a potential carcinogen. More joy!

all: I probably seem like a tela basher and to some extent I am, notwithstanding the fact that I believe it's a great drug and am hoping to take it. There's a lot of loyalty among those who have  reached SVR with tela and it seems unreasonable/offsensive to suggest this is motivated by gain. The same loyalty shows up  with boce, ntz, supplements etc. We all recommend what worked for us.

However it is  hard for me to see how some of vertex's data manipulation can be construed as anything but potentially misleading patients. How can failure to disclose  SVR rates for the 118 ILLUMINATE patients (40%) who did not eRVR  or previous null responders possibly help pts? There have been a couple of posts recently by patients with very  weak past ifn response under the impression tela will give them  a 79% chance. That spin may be good for the stock price but is clearly misleading.

It's great the review is complete and approval forthcoming - but wasn't this expected? The gritty details of who should treat, what PI to choose and when to bail remain. And neither drug co seems to be providing much help in sorting that  out.

[Andiamo1]

Thank you for your very well thought out post.  I do agree with most of what you say, but I am sure that dointime and Susan400 were in the no - riba arm and had to stop as did almost all patients in that arm of the Prove 3 trial due to breakthrough.  The fact that they didn't have Riba seems to indicate that the rash was due to Telaprevir.

I have no knowledge of the ILLUMINATE trial, so I can't comment on it.  

[spectda]

Hi-
I don't want to continue detracting from this important thread (sorry frijole and all).

I apologize if I insulted you. I was generalizing, and considering my timing I can see how my comment about relationships to pharma or financial gain could be insulting and hurtful to you.

Your thoughts and experience are very valuable especially to those who are considering treatment with one of these new drugs.

I should have thought more carefully before I let the dark side take over :)

Take Care
-Dave

[Andiamo1]

Thank you for the apology.  I also have a lot of respect for you and continue to do so.
Eric

[Aaron57]

There is quite allot of free and current data and info on the comparison and treating with DAA's / PI's as well as many other HCV related subjects.
It's a great learning site
Clinical Care Options website.
CCO is a free service but you must register first, (free also)

Subjects such as :

Understanding the Similarities and Differences Among Direct-Acting Antivirals for Hepatitis C

Debating Key Concepts in HCV Management With New HCV Therapies

Current HCV Management Challenges and the Impact of New Agents: The Role of Physician/Pharmacist Teams

Best Practices in the Management of Patients Who Previously Failed HCV Treatment

http://www.clinicaloptions.com/Hepatitis/Treatment%20Updates.aspx

Cheers , Aaron

[Andiamo1]

The bottom line for me is the overall discontinuation rates for the 2 drugs and that appears to be about the same for both drugs.  Both have a higher discontinuation rate than SOC though.

Every comparison I could find with google, gave Telaprevir a slightly higher potency except for non Caucasians where Boceprevir had slightly better or even numbers.  

Willing, what do you mean by "weak interferon response?"  Vertex does provide the numbers for relapsers and null responders.  What other category of weak response is there?

Perhaps I am naive, but I read the ILLUMINATE results and didn't find them misleading.  It was a study designed to test response guided therapy and gave the numbers that would justify it.  There were many other studies designed to show the SVR rate for each category and the numbers are all there.

I am biased towards Telaprevir; it cured me after so many failures.  Vertex pioneered some of the early research and took a tremendous risk and I admire them for that.  I still think I can be objective about it, but I am human, so I am willing to admit my bias could influence me.

[frijole]

This has been posted by pharmaweb.com and for the life of me, I cannot find confirmation of it.  I have looked at the FDA website and it does not show any drugs approved of in may,2011.  I think this is bogus information posted by an investor website who is mistaking the panel approval for the actual FDA approval.  Still, if anyone can find out anything further, I would appreciate it.  It was pos
frijole

THE Food and Drug Administration (FDA) has approved Vertex Pharmaceuticals Inc.'s (VRTX) hepatitis C drug telaprevir and Merck’s hepatitis C drug, broceprevir.

Both drugs are protease inhibitors (PIs) and are designed to block an enzyme that helps the hepatitis C virus replicate. Hepatitis C is a liver disease caused by infection with the hepatitis C virus, which is transmitted through contaminated blood. The infection can cause liver failure and liver cancer


Read more: http://www.pharmiweb.com/pressreleases/pressrel.asp?ROW_ID=40176&utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+Pharmaceutical-News+%28PharmiWeb+-+Pharmaceutical+News%29#ixzz1LK1RFb6f

[Andiamo1]

I googled it and couldn't find any announcement from the FDA for approval, so I assume it's a mistake.

[willing]

frijole: weird. As In understand the process, FDA staff now has to consider  the advisory committee recommendations, make a judgment about how to proceed, write the much anticipated "insert-label" and mail off the approval letters.

However both manufacturers asked for 'add on' approval beyond what the collected PhaseIII data supported. Merck asked for approval for use among nulls and Vertex asked for RGT/24w  for relapsers. From Fuerstein's blog seems the panel  was split on both but with a 50/50 split on Merck and a more favorable split on Vertex. That still seems like a lot of uncertainty before the label can be finalized!  I'm wondering about the 23rd, let alone 7th.

BTW if they do approve 24w protocol for eRVR relapsers will you feel comfortable following it? It's probably fine but given that approval would be based on simulation rather than actual phase III data , some doubt remains until data confirm it.

Andiamo: the boce respond-2 48w stats (71/73, 97%) from table 16 of the staff Merck review seems another area where boce came out somewhat ahead but it's hard to tell how meaningful any of the comparisons are.

Much more important is helping prospective pts sort out whether this will work for them. Success odds from triple tx range from a low of 31% from the tela prior null-responder data to 90s for prior relapsers with early response - a big spread.   The critical  difference is the strength of the ifn response added to the PI.

Up to now, Merck seems to have been more forthcoming about this difference that Vertex. For example table 5 of the fda Merck review doc includes the same information cited in Pawlotsky's recent review: if your VL drop during the 4w lead-in is lt 1 your overall odds are in the 30-40% range, no higher. That's a very useful bit of information for someone planning whether to start taking the PI.

Vertex has provided no equivalent guidance. Their press releases for ILLUMINATE focused on the great odds for eRVRs and buried the eRVR- results. As far as I know, prior to the FDA review, they never released the 31% odds for prior null responders.

Hopefully post approval this will change. If ambassadors or others have any influence with vertex encouraging them to allow pts to make the most informed decision regarding their personal odds with triple tx  seems a good move.

[CoWriter]

Recently, there was a survey for Hep C patients.  The goal, they said, was "to educate doctors".  It asked these questions....

"Why have you NOT taken any prescription medicines to treat your hepatitis C?
How interested are you in starting treatment for your hepatitis C?
What is your genotype?
Which of the following is your primary insurance carrier?
How much has your health care provider discussed with you results from studies with new medications that may soon become available for the treatment of hepatitis C?
What do you think your chances are of being cured of hepatitis C with these new medications?"

When I emailed them and said the questions seemed more like a way of identifying people they could sell a specific drug to, and asked who was paying them to conduct the survey, I was told, "The patient survey is part of a CME series supported by an educational grant from Vertex".

The next day I got an email from their Managing Director who wanted to talk to me on the phone about my concerns but when I said I preferred email so I could quote her, she decided she didn't want to be my pen pal.

Interestingly, the survey reappeared in the UK recently, but this time the goal was to see where docs stood and how they measured compared to their peers....and this time, patients were paid for participating.

But never mind that.  The real reason I'm here is because they are now looking for people in the San Fran area for a "study" that will "help them develop better drugs in the future".  It will pay patients $200 cash and they are offering us a $150 for turning you in, I mean, for referring you asap......and there's this really cool gold bracelet I've been wanting.  So anybody that fits the study criteria please raise your hand.

Co

[CoWriter]

BTW, you fit the study criteria.

Co

[Andiamo1]

??  What in the world are you talking about?

[Andiamo1]

Why don't you spend your time addressing the strengths and weaknesses of the drug rather than imply I am being paid by Vertex.

Is your only way of debating a scientific issue attempting to discredit the person with the opposing opinion?  You should run for president. and not waste your time on a medical forum.

[Andiamo1]

I have come to believe that Vertex is run by aliens.  While standing in line at the supermarket checkout, I read numerous headlines along with detailed photos of saucer like objects hovering over the Vertex headquarters in Cambridge.

One photo showed a direct mind control beam liked to the brain of the CEO.  Who, by the way, is having an affair with Angelina Jolie who is rumored to be carrying his love child.

[nygirl7]

I got that letter yesterday in a PM and I never even took Vertex - I think they sent it out to an awful lot of people on the forum.  If I had taken Vertex I would have gone to NYC for the $200 believe me. Does that make me a bad person? Heck no we all want these drugs to get into the pipeline as soon as possible - look what it DID for Andiamo......after so many times failing treatment it CURED him.

Why would he not support this drug to his fullest ability? I am sure those cured by Boce feel the same exact way and that is where you will run into some problems.......because the people BELIEVE in these things and want everyone to be cured.

It's not like he's out to kidnap Angelina's love child for no reason.

[Rangle]

I always found that drug companies skew the numbers on
what they proclaim to be success rates ...for instance when they first came out with
interferon treatment alone ,....they proclaimed a cure rate of like 25%.... it was more like under 10% if that,..... then when the riba /combo came it was like at least 40% I believe it was less

The question I have with the new therapies if they claim 80%...what is it?

Warmest regards
Rangle

[Andiamo1]

Drug trials have a relatively small number of people participating in them compared to the general population of people with HCV.  The trials are designed in a way that the results will approximate what the result will be once the drug is approved and used by a large number of people.

It is impossible for a trial to predict the result of large numbers of people from a small sample without statistical errors.  Where I fault all the drug companies is that they don't provide the margin of error for these trials.  I believe it must be large, perhaps in the neighborhood of +- 10% -- that is just a guess.  So, I think that is why you see the difference in the real world results.

Many people think the drug companies try and skew the results.  They probably do to a small degree.  It would be too obvious if they did it with large numbers of people and the FDA would never approve the drug if that were the case.

Hope that helps,
Andiamo

[Andiamo1]

Drug trials have a relatively small number of people participating in them compared to the general population of people with HCV.  The trials are designed in a way that the results will approximate what the result will be once the drug is approved and used by a large number of people.

It is impossible for a trial to predict the result of large numbers of people from a small sample without statistical errors.  Where I fault all the drug companies is that they don't provide the margin of error for these trials.  I believe it must be large, perhaps in the neighborhood of +- 10% -- that is just a guess.  So, I think that is why you see the difference in the real world results.

Many people think the drug companies try and skew the results.  They probably do to a small degree.  It would be too obvious if they did it with large numbers of people and the FDA would never approve the drug if that were the case.

Hope that helps,
Andiamo

[Rangle]

My girl is also HCV, after witnessing my treatment she will not treat
The problem for her is, she has HCV related rumatoid arthritis which continues to get worse
Shes in severe pain everday

I'm hoping that the new meds will get approved quickly and maybe she will consider treating (shes an A type geno)

Her doctor proclaims the arthritis will go away once she treats  

Juicing has helped her stay stable except for the arthritis
Her numbers were undetectable, her doctor was miffed

I hope the new meds produce a high SVR rate. I have to think they will tweak them as they go along once approved...A few years back they were talking a bout the 4 of them together?
any further discussions on that?

Regards
Rangle

[willbb]

"  The trials are designed in a way that the results will approximate what the result will be once the drug is approved and used by a large number of people. "
-------------------------------------------------------------------------------------------------------------------------------
I would respectively disagree with this.  The drug trials are designed to get the drug approved ..that is their first and most important priority.

They help themselves immensely  by including the most likely to succeed in their trial..the most healthy (if you will,The ideal candidate to succeed) and most often exclude those that may fail for many reasons.

Once the drug hits the street and EVERYONE treats ..those that are much less likely to succeed than those in trials  ,,only then will the true success percentages be known..about 18 months or so from now.

could it be as much as -10%  ..maybe..only time will tell.

I certainly don"t mean to rain on the P.I parade( I personally am waiting to take one) and I feel these meds will be a huge improvement from what we have now...however the real success data is about a year and a half away..imho.

Will

[Andiamo1]

I hope you get to meet some of the scientists that work on these drugs.  I think you will change your mind about how much the trial is biased.  It is a flawed procedure, but I really don't think the companies, especially the small ones commit fraud.

The selection criteria are fairly general and leave a lot of latitude for the trial centers to make individual participant selections.  I think this is where the bias gets applied.  The individual research coordinators have biases as all humans do, so the patient sample is not as random as I would like.  I disagree with you about the type of bias though: I think they choose people they like or feel comfortable with, not the people that are most likely to SVR.

They included me in the trial though: age 68, stage 3 - 4 fibrosis and failed 6 prior treatments -- not a high probability of success.  I found other people with low probability of success in the trial as well.

[willbb]

I don"t recall saying I thought the drug companies were committing fraud. However, again I disagree with your assertion that their selection for participants is just from the random general HCV populous. It seems like you personally were not an ideal candidate for success ,however the trial I participated in was exactly the opposite of that.The exclusions were a mile long and of the 400 in  mine  and of the 15 or so I got to talk to personally ..it seemed like we were all  very much hand picked to succeed.(Minimal fib.,low enzymes.low BMI ,to name just a few)
Certainly not to say this is the case for all trials,however I have heard this on more than a few occasions.
  Anyway ..time will tell how the percentages all shake out and I still firmly believe  the true numbers will not actually be known until,.like any drug it has been taken by the general populous .

All the best ..Eric

Will

[Trish77]

I think on the one hand that inclusion and exclusion criteria needs to be set so that you have a certain baseline to work with for your trial subjects.  One of the reasons  they choose healthy participants for Phase I so that they can determine potential side effects - those would be skewed if they included people with a variety of health issues as it would become more difficult to determine whether the side effects were due to complications from existing health issues or not.  So I see some merit to having some criteria.

In light of that, I think that Will's point is well taken - "Once the drug hits the street and EVERYONE treats ..those that are much less likely to succeed than those in trials  ,,only then will the true success percentages be known..about 18 months or so from now. "

Not to rain on the SVR parade either....that's the reason why I think it's important to keep talking about side effects that aren't necessarily included in drug company literature on a product and how a drug impacts those that take it once it hits the market.  There's simply alot that isn't known until a drug hits the market, is in wide circulation and those controls are no longer in place.  

However, we have to start from somewhere and using controls on trials makes sense to me to start with a baseline that we can look at to determine how the drug performs under certain conditions.  

Having said that....many times over my life I've seen the conflict between profit motive and integrity of the deliverable between those responsible for the deliverable and those responsible for the profit margins.  There have been a number of times where drug companies have been fined for not protecting the consumer and it's not the drug company that puts the consumer first at those times, it's the doctor (most of the time) and the patients.  As we participate in drug trials and our lives depend on the product the drug company delivers, I think it will always be a case of "buyer beware" and we will always have to pore over details of trials and they way they are conducted and then continue to be advocates once the drugs are in the market and in "Phase IV".

Trish

[Trish77]

"The selection criteria are fairly general and leave a lot of latitude for the trial centers to make individual participant selections.  I think this is where the bias gets applied.  The individual research coordinators have biases as all humans do, so the patient sample is not as random as I would like.  I disagree with you about the type of bias though: I think they choose people they like or feel comfortable with, not the people that are most likely to SVR. "

All the more reason that we need to keep talking about our experiences with the drug and it shouldn't be taken as bashing.  We end up with two-tiered inclusion and exclusion criteria - at the qualification level by the drug company themselves and at the research facility level when they have their own influence over who is in and who is out and what their own comfort level is with using the latitude the trial allows them, i.e. with using rescue drugs or not.  My trial allowed use of them but my treatment team was comfortable using procrit/eprex but not neupogen. So while I readily got procit, I had to fight a long time for neupogen.

"They included me in the trial though: age 68, stage 3 - 4 fibrosis and failed 6 prior treatments -- not a high probability of success.  I found other people with low probability of success in the trial as well. "

Not to be entirely cynical...because I'm not....but your trial was for non-responders and not sure they could have excluded you based on how many times you didn't respond or they would have had to state that.  For them to have Telaprevir prescribed on-label for non-responders, it has to have been tested amongst that group of people - do I understand that correctly?  

Just the same, research facilities have been known to be compassionate in their choices also and deserve some recognition of this fact.  I also know people who were included that had a higher risk level and a more desperate situation - advanced liver disease - in hopes they would get a cure  Thankfully, this occurs also.

Trish

[Andiamo1]

Will

You didn't say anything about fraud and I put words in your mouth - sorry about that.  It's just that if the trial is intentionally stacked to produce better numbers than might reasonably be there in the general population, that is fraud by definition.

If the exclusion - inclusion criteria screen out people that are likely to fail, then the results would be skewed as you say.  The Prove3 trial that I participated in did not do that.  Profit drives many people, some to be dishonest.  High ideals also drive many people, particularly scientists.

I wish I could describe statistical analyses more effectively, so that people could understand how trials work.  The standard deviation is very large in these types of trials, so that even if everyone is ethical and honest, the numbers will never match the real world population.

Thanks for a rational discussion.
Eric

[willbb]

  I think we are on the same page with just a couple of very slight variations  :)

  Lets hope the end results we will be looking at in a couple of years  are what we are all hoping for....

Best...

Will

[Andiamo1]

".but your trial was for non-responders and not sure they could have excluded you based on how many times you didn't respond or they would have had to state that."

But they could easily have cut the age to 60 or 65, since most patients are younger.  They could have made stage 3 the cutoff, but they went all the way to stage 4 compensated.  The limit of 70 for age and stage 4 compensated added many low probability SVR patients into the program.

We could butt this back and forth forever without agreeing.  To conclude, I don't think trials are particularly accurate, at least nowhere near as accurate as most people think.  I don't think many companies intentionally skew trial results.  I am sure some do, but most do not.

[Trish77]

"It seems like you personally were not an ideal candidate for success ,however the trial I participated in was exactly the opposite of that.The exclusions were a mile long and of the 400 in  mine  and of the 15 or so I got to talk to personally ..it seemed like we were all  very much hand picked to succeed.(Minimal fib.,low enzymes.low BMI ,to name just a few)
Certainly not to say this is the case for all trials,however I have heard this on more than a few occasions. "

I think this is another excellent point, that not all trials and not all drug companies and not all research teams and not all research centers and not all ethics boards at these research centers are created alike.  So what may be the environment for one trial through the various iterations it goes through will not be the same for another.  On top of that, it has to get through the various Phases with each of those parameters in play.

Lots and lots of variables by the time a drug hits the market.  On the other side of this, there are stringent FDA-regulated checks and balances that have to be observed, so I don't mean to be overly pessimistic or optimistic about it all….just realistic.  A bit of a trick sometimes. :)

[Trish77]

"We could butt this back and forth forever without agreeing. To conclude, I don't think trials are particularly accurate, at least nowhere near as accurate as most people think. I don't think many companies intentionally skew trial results. I am sure some do, but most do not. "

I'm not sure agreement is required. :) You can present the information quoted above and different people will see it differently.  Different points of view don't necessarily render one of them correct and the other incorrect, simply different.  I think the dialogue is important and people have plenty of information to draw their own conclusions.  I personally happen to learn from reading multiple comments and points of view to be able to formulate my own conclusions and make decisions that are best for me.  I find the dialogue in general beneficial and dissent or disagreement is not necessarily a bad thing.

Trish

[Trish77]

"But they could easily have cut the age to 60 or 65, since most patients are younger.  They could have made stage 3 the cutoff, but they went all the way to stage 4 compensated.  The limit of 70 for age and stage 4 compensated added many low probability SVR patients into the program. "

And btw....that's good information, puts additional perspective on it.  Thanks for that.

Trish

[CoWriter]

"Why don't you spend your time addressing the strengths and weaknesses of the drug rather than imply I am being paid by Vertex."

That was not at all what I was saying.  I don't believe you're being paid by anybody, as a matter of fact.  I was just telling you what they're doing.  The fact that they're trying to find patients asap makes me very suspicious.

"spend your time addressing the strengths and weaknesses of the drug"

As a matter of fact, I tried to do just that.  The other day I posted a comment in answer to something written on PI's on a financial magazine and 5 minutes later it was deleted.

Here's part of what I said.....


"Treatment failure with the triple combination of pegylated interferon, ribavirin and a protease inhibitor results primarily from an inadequate response to pegylated interferon and ribavirin, which leads to uncontrolled outgrowth of resistant variants selected by the protease inhibitor. People who treated in the past and had a poor response to interferon+Ribavirin have only a 20-30% chance of success with triple therapy.

Regarding your comment...."The respective resistance rates for both boceprevir and telaprevir are relatively low, so this is not an issue expected to derail approval. It's more of a concern about how to treat or re-treat patients in the "real world" clinical setting if or when resistance to either drug occurs."

A selected resistant variant must have the capacity to propagate in order to fill in the replication space left vacant by the susceptible ‘‘wild-type’’ virus during drug exposure. Thus, a highly resistant but poorly fit virus will be less clinically significant than a less resistant but fitter virus that can replicate efficiently in the presence of the drug. Plus, some viral variants that show low-level resistance in vitro may be more damaging in vivo than variants with higher-level resistance.

"if or when resistance to either drug occurs."

In patients who failed triple therapy, experienced a breakthrough during treatment or relapsed after the end of therapy in the phase 2 and 3 clinical trials of telaprevir or boceprevir, protease inhibitor-resistant viral populations were dominant at the time of relapse in MOST IF NOT ALL cases!

Last but not least, "treatment experienced" patients include relapsers and slow responders. On the other hand, "difficult-to-treat" patients include null responders, people with unfavorable genetic markers of interferon responsiveness, specific subgroups such as African Americans, patients with advanced liver disease, liver transplant recipients, HIV-coinfected individuals, hemodialysis patients, and other immunosuppressed patients. All patients who have not yet been included in clinical trials.

No wonder their results look so good."

Co

[Andiamo1]

You do raise interesting points. and I agree with you about the resistant strains.  You are mistaken about the Vertex trial though.

The prove 3 Vertex trial did not exclude African Americans, Null responders or people with advanced liver disease as long as they were compensated.  I was stage 3 - 4 transitional and 68 years old and they included me in the trial.  I think it was quite reasonable of them to exclude liver transplants and HIV co-infected people since they have a different set of problems and would require a trial of their own.

[coeric]

"Treatment failure with the triple combination of pegylated interferon, ribavirin and a protease inhibitor results primarily from an inadequate response to pegylated interferon and ribavirin, which leads to uncontrolled outgrowth of resistant variants selected by the protease inhibitor. People who treated in the past and had a poor response to interferon+Ribavirin have only a 20-30% chance of success with triple therapy

cowriter - very well said and willing has made the same point too.  if you were a treatment naive that is considering therapy, would you insist on a lead in with interferon and ribavirin?  if yes how long would the lead in last and what would be the magnitude of viral load decrease you would want to see before adding the P.I.?  for instance would a 1 log decrease in 4 weeks with interferon and ribaviron be adequate?   i have the geno1A and am IL28 CC genotype with compensated cirrhosis.  thank you.

[lapis]

I have been following this thread for days and days, and learning so much.  I just want to say that I appreciate you guys, especially Andiamo and CoWriter and Trish and Willing and Will, for staying in it, for continuing even when it has been uncomfortable, and sharing your knowledge and thoughts so clearly.  This is truly one of the strengths of this board, that such knowledgable people are willing to disagree and still keep posting till some understanding is reached, and points are made.  It takes patience and fortitude to stick with it, and I respect you all for doing this.  

So as a Telaprevir trial participant, I guess they might have checked my DNA to see if I'd have the best genetic markers for tx success, and that might have played into their choosing me, along with other factors? They had my liver bx results (Gr1St1-2) and VL3.6M. They also ran an EKG for heart function baseline.  My BMI is 32-33 and I was 55yrs old and tx naive when I started the trial.  I wondered about my preexisting health conditions of hypothryoidism and a total knee replacement, wondering if these factors might exclude me, but otherwise I was pretty healthy except for weight and VL.  I did meet the stated inclusion criteria for the trial, now I'm wondering if there were other selection criteria which were unstated. And this sort of follows y'alls previous discussion above about how trial partipants are actually chosen.

I believed I had a lot of strengths going into tx but I'm sure I got a double dose of anemia from the synergistic effects of both the Telaprevir and the Ribavirin, since we had to dose reduce my Riba after wk 3 for the next 3 weeks.  After another 4 weeks on proper dosing it was again reduced for 4 wks before resuming recommended dosing.  So....for the first 15 wks of tx, I went from 1200 Riba to 600 for wks 3, 4, 5, to 1000 for 2 wks, then to 1200 for 2 wks then back to 600 for another 4 wks before returning to 1000.  Now I understand that this decision process is called RGT, response guided tx.  Although the anemia was bad at times (lowest Hgb was 9.1), I'm grateful I didn't have to take Epo or whatever other meds are used for this.  And for me, this shows that RGT really does work, or at least in my case it did!

I want to learn more about Vertex and how these clinical trials are run.  This discussion has piqued my curiosity.  I am clearly biased toward Telaprevir and my treating hospital.  They treated me for free and gave me excellent care.  My total tx time was only 24 weeks which is a miracle in itself in my mind!  I don't have any problems or experiences or negatives to say about Boce; Telaprevir has my allegiance simply because I know it intimately, I know what it did to my body, and it worked for me.  I will always be grateful.  The mild rashes I experience now, which are new to me since tx, are still insignificant when I consider that I have SVR.

Pardon this thread if I've rambled, I just wanted to finally get in on this discussion.

Lapis

[Andiamo1]

I can't say I have completely thought this through, but I'll say it anyway.  I think a case could be made that if you plan to treat, you should treat with a PI.  Interferon is by far the most dangerous drug in the mix and the odds are in your favor that you will treat for a shorter length of time, thus have less interferon exposure and have an SVR.

If you fail treatment for any reason and have a resistant strain survive, you still have the option of treating with the newer drugs that are polymerase inhibitors and don't have a
problem with PI resistant virions that survive, but are not as strong as wild type virions.

You could make a case for waiting for the new drugs and not treating at all, but I think it is foolish to treat with the current SOC given the state of the art in HCV treatments.

I think lead ins are a waste of time for people that have treated before.  All the data is known before a patient starts treatment with a PI.

I think a four week lead in will screen out people that would SVR if they treated with triple therapy.  I was a slow responder that had a 2 log drop by week 20 and triple therapy worked for me.  On top of that it adds 4 weeks of uncomfortable life and increases the odds of interferon sx.

If an individual has a weak immune response to interferon and can't eliminate wild type virions, resistance will not matter: they will never reach SVR with a PI and SOC combo or SOC alone and will need the new drugs.  Once the new drugs are available, PI resistance will not matter (I think).  

So why not just take a gamble and jump in if you need to treat and wait if you don't need to treat?

What do you think?

[frijole]

This is the link to  FDA approvals.  You can see what has been approved so far in May, and neither BOC or TEL are among the drugs.  As a curiosity because I don't know how this all works, I see that a lot of the approvals are for labeling, not the actual drug approvals.  Thus I come to the conclusion that there will be a lot of label modification to both drugs after the initial approval.


http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Reports.ReportsMenu

I read this thread with great interest.  Willing, I appreciate the depth of your studying and wonder how you are managing to keep such a great focus while treating.  Am I ready to treat for 24 weeks, being a relapser who previously treated for 56 weeks?  I am not.  However, if I were to clear after being on (either) PI for 2 weeks, I might be willing to change my mind.  One of my greatest concerns too is whether to do the lead in or not so any comments made on this subject are appreciated.

frijojle

[coeric]

one of my concerns is that doctors will treat naive patients with a simultaneous start for all three drugs, which i guess is the way most of the telaprevir trials were run. if a patient does not have an adequate response from the interferon the patient will end up with PI resistant strains.  and this patient will probably not be able to use the PIs for a least 2 to 3 years or perhaps ever?  

And then there is the whole issue about the null responders.  if 67 to 69% of previous null responders fail to make it to SVR with telaprevir, won't these patients also be denied future use of PI? perhaps someone with minimal fibrosis would be well advised to hold of tx until the polymerase inhibitors are available.

my platelets dropped below normal a little over 2 years ago and are running about 110,000 so i am running out of wiggle room.  thank you one and all for this discussion.

[Andiamo1]

My Bias.

A number of people have said that they think I have a Telaprevir bias.  I do.  I was a very poor candidate for SVR and thought, as many people here do, that no trial would admit me, since I was likely to fail.

Vertex accepted me into the trial even though I had failed multiple times, was 68 years old and had advanced fibrosis (stage 3 - 4 transitional).  So I have a loyalty to Vertex for including me in the trial at a risk to them AND curing me to boot.

I have been strident here and I apologize to anyone that I offended.  I do get very angry when I think someone accuses me of being pro Vertex because of some monetary concern.  I get even angrier when I hear people say that Vertex skews the result; because of how they treated me, I believe they don't skew the results.

There are no excuses for being rude, so again, I apologize if I have been rude to anyone.

[Magnum]

I'm a little confused. Your situation mirrors mine in many ways. Are you undetectable?

Magnum

[willing]

coeric: whether to jump into the triple tx pool for those with with a history of weak ifn response is indeed the 64K question. For relapsers,the decision  is obvious. The only remaining issues are choosing PI/sx and settling on tx length. I'd argue that for an F2 prior null the choice  should also be obvious - wait for a two DAA combo, quite possibly including boce/tela.

For those running out of liver time, much harder decision. The information provided by Merck and summarized on table 5 of the FDA staff review

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/UCM252341.pdf

seems the best information currently available in making the decision. Failure to achieve a 1log drop during 4w lead in points to much reduced odds.

Vertex unfortunately has released no similar information, though they have it. The lead-in arm of REALIZE (labeled C216 in the FDA docs) included 264 patients, so Vertex clearly knows the impact of lead-in response on outcome but they have not released this, either in press release or in the FDA submission.

Long term tx with a PI and weak ifn response will  lead to a thriving population of progressively more fit PI-resistant virions, so early stopping rules are key, particularly in the absence of sequence information. The impact of enriching the proportion of PI resistant  virus by unsuccessful triple tx remains a complete mystery - there is no retreatment data yet I tend to agree with Andiamo that this isssue is probably overblown. Resistant mutations  fade over time and even if failed triple tx increased your % from .00001 to .001 re-tx with boce/tela will still be knocking out the great majority of wild type.

Andiamo: no need to apologize! Vigorous defense of tela will help many here make a better choice on the merits. As lapis noted, this has been an interesting thread.
Agreed that patient selection bias is probably a non-issue : if it's too glaring it'll show up in stats for the randomly assigned control group.

However, what possible justification can you see for Vertex's failure to release the data mentioned above?  or for not including null-responder and eRVR- data in their press releases (though they did finally release this to the FDA).   If they really were interested in patient welfare, releasing all relevant information seems more important that having the newly hired sales team build up lists of (potentially misinformed) leads.

[Andiamo1]

I have no justification for them not releasing data.  They think they are much more forthcoming than Merck.  I don't know if that feeling is justified or not.  They are a small company and could have been so focused on FDA questions that they just didn't pass all the data to their PR department.  I am just guessing at that.

I have spent some time with them and I am convinced that they believe they have presented all the data.  That does not mean they did though and I have no explanation if there is a discrepancy between what you believe and what they believe.  I would love to pursue it and I will if I ever get to meet their upper management again.

Vertex believes that the virus will revert to the wild type within 2 years of treating.

[coeric]

thank you both for your opinions that the resistance is overblown. willing i am impressed with you ability to continue contributing considering your situation.  makes me thing i might be able to tx.

it is interesting that vertex has not released the lead in data.  but perhaps as was suggested earlier - vertex is interested in presenting tela as a 6 month tx for most and not a 7month tx.  
eric

[Andiamo1]

Vertex never had a trial with a lead in, so they have no data to present.  At least that is to the best of my knowledge.

Their scientists do not believe that a lead in is useful.  

Eric

[coeric]

i am delighted that there are two DAAs about to be approved.

the following is from the Antiviral Drugs Advisory Committee April 28, 2011 Briefing Document.  perhaps the results of this study lead the investigators to conclude that the lead-in was not needed.  also you make a good point about not prolonging the tx longer than is necessary.  thank you.

C216 also evaluated the effect of a 4-week lead- in period with Peg-IFN/RBV before the telaprevir-treatment phase
Overall, a lead-in with telaprevir relative to Peg-IFN and RBV did not result in added clinical benefit relative to simultaneous start of telaprevir and Peg-IFN/RBV:
SVR24 rates were similar between the T12/PR48 and T12(lead-in)/PR48 groups for prior relapsers, prior partial responders, and prior null responders. The difference in SVR24 rates (T12/PR48 versus T12(lead-in)/PR48) with 95% CI was -4% (-6.4%, 10.4%) for prior relapsers, 5% (-26.2%, 12.64%) for prior partial responders, and -2% (-12.3%, 17.7%) for prior null responders.

[willing]

Vertex definitely  has data on patients treated with  lead in and has submitted part of this to the FDA. See page 60 of the 147-page Vertex submission which spells out the study design for trial C216(aka Realize). The lead-in arm included 264 patients.

Unlike Merck, Vertex submitted no data on how response during that lead in affected outcome. The Merck data shows a very strong impact of poor lead-in response on outcome.  It would be  helpful to patients planning triple tx to see how this played out for tela, particularly across different prior tx groups. We can speculate about why this has not been released  -  my hunch is business interests  beat out patient interests.

The benefit of lead in is not a significant improvement in outcome - but critical information about what your personal SVR odds are with triple tx before the first PI pill.  Relapsers don't need to bother,  but anyone with a weak past response who is uncertain about whether it's worth trying  will benefit.

[Andiamo1]

I am surprised that they did have a trial with a lead in.  I do believe they think it has no value, but you could be right and it is business.  

I googled the trial and found many references to the lead in data.  This is one example:

"SVR rates for the telaprevir simultaneous start arm and the delayed start arm were 64% and 66%, respectively, overall, based on an intent-to-treat (ITT) analysis. For the primary analysis, the SVR rates for the telaprevir simultaneous start arm, delayed start arm and control arm, respectively, were 83%, 88% and 24% in relapsers (p<0.0001); 59%, 54% and 15% in partial responders, (p<0.0001); and 29%, 33% and 5% in null responders, (p<0.001)."

It looks like the results were withing the standard deviation of the trial.  So, I have no idea why the data was not submitted.

[Andiamo1]

Personally, I would never take interferon 4 weeks just to see the effectiveness of the treatment.  I would sooner hang by my thumbs.  There is a strong possibility that potential SVR candidates would be screened out.  I would wait for a better test than a lead in.

[Andiamo1]

I apologize for these scattered posts: I have severe insomnia and ADD that has plagued me since I treated with SOC in 2002.

I think we have to analyze how many people that would SVR were screened out due to the lead in test; in other words what errors took place in the screening process.  I think enough data is there to do it, but it's beyond my ability these days.    The question is what percentage were screened out in the Boceprevir trial and how does that compare with the failure rate when there is no lead in screen?

Given the standard deviation of these trials, say 5%, which we can only guess at, the results of the two trials are identical.

Lots more analyses here before we conclude that a lead in is beneficial.  I wish I could do it :(.

[coeric]

thank you. you have a great point about screening people out of therapy with a lead-in. Do you suppose there are patients in the boce trials that would have achieved SVR if they had been allowed to continue?

your points are relevant.  i am thinking that a shorter than 4 week lead-in might be better.  a while back i recall a study that suggested interferon response and SVR could be predicted with-in 24 hours after the first interferon shot.

it might be useful to know my response to interferon/ribivirin to facilitate response-guided therapy.  say instance i have a weak interferon response and after 2 weeks of innterferon/ribavirin the viral load is reduced only 75%.  and at this point i want to continue on.   the way forward might be to try to maintain a significant dose of ribivirin with the aid of epogen when the anemia kicks in.   on the other hand suppose by some miracle i am undetected by 2 weeks.  i might be more inclined to reduce the ribavirin when the anemia starts.  

i am also  experiencing loss of attention.  don't know whether its due to advancing age or this silly disease.   i want to thank all the folks like yourself who have been cured and continue helping us newbies out.  thank you one and all.

eric

[Andiamo1]

I think a lead in is imprecise at best as a screen.  I was a slow responder and became undetectable at week 20.  I relapsed after EOT.  I was a very rapid responder when I treated with triple therapy and am SVR 3 years post treatment.

The data presented is too vague to use as a way of seeing the effectiveness of a lead in as a screen. I have not seen the standard deviations published for any trial, so I assume it's large enough to make the differences between a lead in and no lead in meaningless.  I don't have any proof of that, but a trial of a few thousand people used to predict the response of a few million people must have a large standard deviation.  If it's +- 5% then a difference of up to 10% between 2 trials is meaningless.  I hope it's not that large, but who knows?  And that's saying the trial selection is totally unbiased and I don't think many people believe that.

Eric

[willing]

coeric: anyone doubtful about whether triple tx will work given their past ifn response should look at the data directly - it's well summarized and the difference is stark. The 90-page Merck submission is at

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/UCM252343.pdf

The SPRINT-2 results (naive, 1097 pts) are in Table 8, pg. 42 and the RESPOND-2 results (previous tx failure,  413 pts) are in table 15 pg 53.

Having a 1 log drop by w4 makes approximately a  40% difference in SVR outlook - nothing vague about that.

Any early cutoff decision will exclude some potential SVRs - even continuing with detectable VL at w24 leaves a 2-3% chance of SVR.  And for many continuing with a 30% chance will  still be the right choice. However it's good to know what you're signing up for.

Testing earlier can give an early peek at how it plays out ( I tested at 24h and 48h post) but there's no equivalent data similar to what's given in those two tables. Hopefully Vertex will at some point let us know their side of the story.

Andiamo: though you didn't clear until w20 it looks as if you'd still be classified as a relapser by the Vertex criterion so your odds with them would have been about 80%.

Re standard deviations, you're right that they don't appear to be explicitly included but since what's being measured is a difference in response rates they are easily calculated from  counts. The standard error of the difference of two response rates is
sqrt( (p1*(1-p1)/n1+ p2(1-p2)/n2 )
where p1 = svr1/n1 and p2=svr2/n2 are svr %s in the two groups.

Agreed  that confidence intervals (which incorporate the standard error) are more informative than point estimates. For example, it makes no sense that a lead-in would reduce your SVR odds. The improvement may be small but shouldn't make things worse.

In fact looking at the confidence intervals coeric quoted above shows that the CI for the partial responders is much wider (over twice) than the CI for relapsers, making that point estimate more suspect. Of the 662 pts in the REALIZE, 354 were relapsers but only 124 partial responders so you'd expect a noisier estimate in that subgroup.

[Andiamo1]

Wouldn't you need to use multiple trials and calculate the difference between each of them for the same values?  Since this is a sample population of a larger group, isn't there a slightly different formula where you need to subtract 1 from the denominator?.

In any case, one standard deviation is likely to make some comparisons irrelevant, don't you think?

[Andiamo1]

"Andiamo: though you didn't clear until w20 it looks as if you'd still be classified as a relapser by the Vertex criterion so your odds with them would have been about 80%."

That would have been evident after the Prove 3 trial, not before when they accepted me into the trial with no data at all on prior treatment.

"Agreed  that confidence intervals (which incorporate the standard error) are more informative than point estimates. For example, it makes no sense that a lead-in would reduce your SVR odds. The improvement may be small but shouldn't make things worse. "

Publishing the standard deviation would give us a better understanding of how to interpret the numbers.  For example: if the Telaprevir trial had results that showed SVR rates of 78% with a lead in and a standard deviation of +-3% then the results would read SVR rates of 75 - 81%.  If Telaprevir had results of 75% with a standard deviation of +-3%, then there results would read between 72 - 78%.  These numbers are within the standard deviation of the trials and are statistically identical.

[willing]

>That would have been evident after the Prove 3 trial, not before
agreed - but I believe it also suggests your positive experience with tela may not be accessible to someone who goes into triple tx as a prior null, not as  a relapser

>isn't there a slightly different formula where you need to subtract 1 from the denominator?.
yes, but that shows up in estimating the standard deviation of a continuous variable eg
http://en.wikipedia.org/wiki/Standard_deviation
which would be applicable if comparing a measurement like say HgB decline. However in comparing SVR rates the distribution is a discrete one with an outcome like a coin flip so the formulas differ. A description, including worked example, is here
http://www.stat.yale.edu/Courses/1997-98/101/catinf.htm
at the label "Comparison of two proportions".

Confidence intervals can shed some additional light on comparison because they incorporate the noise expected in estimates made from samples of a given size.

For example did Vertex's patient selection procedure for Advance  result in an easier-to-treat sample than in Merck's equivalent Sprint-2 study? Different SVR rates in the randomly assigned placebo arms would show this effect. For Advance, 361 pts were  assigned placebo and 166 reached SVR( 46%). In Sprint-2 363 pts were assigned placebo  and only 137 reached SVR (38%). How likely is an 8% difference to arise by chance alone in samples of that size if there were really no difference in patient screening?

Applying the equation from that Yale stat page above gives a 95% confidence interval of (0.01, 0.154)  Interestingly the CI does not include zero suggesting that for samples that large an 8% difference is unlikely by chance alone - but the lower bound is close to zero (they cheated, but only a little bit?)

The same approach could be used to sort out whether the difference in SVR rates among naives between tela and boce could easily have arisen by chance or suggests  separate underlying distributions (haven't done this).

[Andiamo1]

"How likely is an 8% difference to arise by chance alone in samples of that size if there were really no difference in patient screening? "

Possibly likely depending on the standard deviation.  This is a small selection out of a large group.  40% has been the published number for many years for SOC, so I would assume their number is quite accurate.

If you look at all the published SOC SVR rates, they seem to be in the 40 - 48% range and have been for many years.

[mremeet]

I'm really happy to see that Telaprevir (formerly VX-950) is successfully making its way through the approval process and appears to be finally coming to market; it's long overdue in my opinion.

As a brief introduction for those who don't know me, I was in the Prove 1 trial which was the first full length triple therapy Telaprevir trial conducted (starting in summer of 2006). I received Telaprevir (I was not in placebo group) along with riba and IFN. Initially I started off in the trial without any undue side effects, other than a nasty flu like reaction to the first IFN shot (which is fairly common and cleared up by the 2nd shot). I was doing ok until about week 6 or so (it's been awhile, so my dates might be a bit off). That's when I started to get a peculiar rash that seemed to grow in intensity over several days. At first it wasn't clear what it was because there was no background data or experience to pull from. And since both IFN and riba can also cause rather severe rashes (either individually or in tandem) in some people, it wasn't clear the Telaprevir was the offending agent to either me or my doctor.

I tried to deal with the rash through week 6, but it just got worse and worse. It appeared as if it was going to derail my treatment which was an extremely depressing and upsetting thing at the time. My doctor just kept telling me to hang in there and let’s see what happens etc (again, mostly due to plain ignorance about the unknown side effect profile of Telaprevir at the time). By week 7 it was too much and something had to be done, including the possibility of discontinuance. I went to see the doctor and he reluctantly prescribed prednisone, which is an oral immunosuppressant. Immunosuppressants are essentially the opposite of immunostimulants and normally you would never want to take both at the same time. Interferon (and perhaps ribavirin) are immunostimulants, and normally you would never want to take a drug that would counteract their effects in any way during HCV treatment. Doing so could easily result in treatment failure, especially for the already hard to treat geno 1 patients. At the time I knew this and really didn't want to take prednisone, but due to the severity of the rash, I had no choice.

Prednisone is commonly used to stop nasty allergic reactions (which may be caused by all manner of things) and is also used to help prevent organ rejection in transplant patients. It's powerful medicine and it can have very bad side effects if overused (or misused). But the prednisone was a magic bullet to my rash at the time. My red, bumpy, itchy rash evaporated within hours of taking the medicine at first. It worked great and it appeared I was back on track with the trial, although with more bridges to cross in the weeks to come.

When prednisone is prescribed to address an allergic reaction of any type, usually two things happen. First is that the offending allergen and mode of exposure is identified and eliminated. Secondly, prednisone is initiated at a relatively high dose initially; I believe for me it started out at about 40 mg daily. Then the dose is tapered off over about 2 weeks by gradually lowering the dosage received as the days tick by. The reason this is done is because if you suddenly chop prednisone dosage off to zero overnight, your body can experience a severe allergic relapse in response to the abrupt change in internal body chemistry - even in the absence of the original allergen (I forget the exact mechanism but I think it might have something to do with histamines etc).

So after my initial positive reaction to prednisone, I began tapering down as the days went by. I also continued on full triple therapy which included the full dosage of telaprevir. Unbeknownst to me and my doctor at the time, I was one of the unlucky ones that had developed a severe allergy to telaprevir after about 5 weeks of exposure. The prednisone was successfully thwarting my allergic reaction to the drug as long as the dosage was high enough. But once my prednisone dose tapered off to about 5-10 mg daily, my body started once again to react to the telaprevir, except this time it was *different*.

Basically the rash exploded back into full flower at the lower prednisone dose, except this time it appeared much more ferocious. It was frightening how aggressive it grew and spread. My doctor told me to stop the Telaprevir, which I did promptly out of sheer fear of what was happening. He also told me to jack the prednisone dose back up to the original starting dose of 40mg, which I did. But this time, nuthin' doin. The rash would not go away, even several days after stopping the Telaprevir. So my prednisone dose was increased more and more, until basically I was eating it like candy. I maxed out at about 80mg a day, but the rash STILL wouldn't go away. I was getting terrified and sleep deprived and delirious (with daily rantings here on this forum lol) and my doctor was helpless to come up with any more answers on how to deal with it other than also stopping the IFN and riba as well. But I didn't want to do that, I wanted to finish off the virus and since I was only 7-8 weeks into treatment by this time I didn’t want to risk stopping and come out of it relapsing with a PI resistant strain (I knew I was UND at 3 weeks because I had a 2 IU/ml > PCR done "offstudy"). So as a last ditch effort I went to the emergency room with my leprosy face and body. All the people at the front desk gave way immediately as I walked forward, fearing I was going to give them whatever crud I had. It was pretty hilarious actually.

So the emergency room administered an IV drug called solumedrol, which again is a powerful immunosuppressant usually given to patients experiencing life threatening allergic reactions to bee stings, poison ivy etc. If you've ever seen those old Lon Chaney werewolf movies with the time lapse photography where his face is transformed from his werewolf form back into his normal self, then you know what happened to me. Because that's exactly what happened to my skin once that solumedrol flowed into my veins. You could literally see the red color draining from my rash as the drug took effect in just minutes. You could actually see the raised bumps start to flatten out, and within 15 minutes I was a new man, albeit completely drained from the whole ordeal. It wasn't an ideal situation at all because the solumedrol was very powerfully suppressing my immune system and weakening the effects of the IFN and riba to the extreme. I dreaded the thought that the virus was getting a foothold in my body again just as it was probably tottering on the brink of extinction. But it had to be done and I would just have to take my lumps in terms of risking a lost SVR.  cont...

[mremeet]

cont...Anyway, long story short, I limped along after that for a total of about 40 weeks of tx. I missed 1 IFN shot during the rash fiasco and my riba dose was cut back from 1600mg/day (I think?) to about 800-1000 daily. I could only tolerate about 800mg of riba a day towards the end  because it irritated my skin so bad. Although the major rash was gone, my skin was still very sensitive and remained so until the end of treatment. I literally scratched the eyebrows off my face I itched so bad, but yet I had these freakishly long eyebrows. I looked like a Dr Suess character. Well, sort of a cross between Dr Phibes and a Dr Suess character.  ;-)

But guess what? I would go on to be cured. And looking back on it, now with 20/20 hindsight the Telaprevir was a critical hingepin in my successful treatment. It worked, no doubt about it. Any thoughtful and reasonably well informed doctor prescribing Telaprevir+IFN+riba nowadays (as opposed to the summer of 2006) should now know about the typical rash profile that occurs in those unfortunate enough to get the PI rash. The solution to it is to simply stop the drug once it gets going. Simple as that - identify it properly and stop it. Telaprevir works it magic over a relatively short period of time. Usually it does what it's going to do within about a month. The IFN and riba do the rest and they require a longer period of time to finish the job. But the point is that they can finish the job without the Telaprevir. That is, after it has decimated the virus to the extent that only a mopping up of stragglers is required in the final portion of the thankfully abbreviated treatment. Telaprevir offers tremendous utility, even in those that get the rash. As long as you can tolerate it for a few weeks, it can greatly help those people too (as it did me). You just take it as long as you can, and simply stop the drug when you have to and continue on with the other two drugs. With what we know today there's absolutely no need for anyone to go through what I did and others (namely "prettydamscared").

In fact, I've come to believe that in my case I was actually SVR by week 7. Of course there's no way for me to know for certain, but I know I was UND by week 2 and less than 2 IU/ml by week 3. I also had a robust reaction to the IFN and ribavirin with a very nasty flu-like reaction to my first shot (indicating a healthy physiological response).  I believe the telaprevir in conjunction with the other drugs did the virus in in a way that made my (1) early discontinuance to the Telaprevir, (2) prolonged exposures to prednisone and solumedrol and (3) my reduced riba dosages afterwards - irrelevant after week 7. And I know from some of the concurrent UK Prove 1 study participants (dointime etc) that there was a young woman who crashed and burned with a PI rash about the same time I did into treatment. Except she bailed and discontinued early, but yet she SVR'ed anyway. I know there have been others who match this profile as well.

Lastly, someone mentioned dointime and some others above. Dointime failed treatment but it wasn't because she burned out on the rash. She did get a rash, and she did suffer from it. But the main reason she failed tx is because she was not receiving ribavirin. At the time it was not known if ribavirin was an essential element of IFN+Telaprevir therapy. We now know that it is. Several others also failed for this reason, unfortunately. Also, prettydamscared was in the same trial I was in and we treated together with the same doctor. We both experienced  the rash and were treated with prednisone as described previously. Except she didn't take the solumedrol like I did.  She made it to about week 40 like I did and appeared to be well on her way to SVR-ing, but unfortunately was killed in a car accident about 3 months post tx.

Anyway, my vote is definitely in favor of Telaprevir. If it can work for me, it can work for almost anyone. You just gotta know how to use it and very carefully monitor how things are going as you move through those most critical early weeks of tx.

[nygirl7]

Wow meet I had forgotten all about all that (and prettydamscared).  It's no wonder we all care about each other so much we have been through more than anyone could understand had they not gone through it with their internet support group.

Man I really just almost cried.

[mikesimon]

That's a great story.
You fought and won one very hard battle.
Solu-Medroll is one serious drug - yes indeed.

Be well,
Mike

[Javi1962]

wow great story!!! I am scared for treatment because I have bad psoraisis (psoriasis) and not sure how that is going to do on treatment, due to the immune boost I will recieve may cause psoraisis (psoriasis) to flare and go crazy! anyone experience this? and I wonder if solu-medroli will help with this? I know prednisone is a drug they prescribe for psoraisis (psoriasis)

[Andiamo1]

I can only describe my own experience.  I never had psoriasis before I treated with interferon.  After I completed my next to last treatment, I developed a mild case of it.  When I started my last treatment, it disappeared!  After I stopped, it came back once again.

My conclusion from this is that no one has a clue what psoriasis and interferon have in common.  Some people thought it might be a predictor of a Telaprevir rash, but I didn't get the rash.  The standard thinking is that the combo of interferon and ribaviron will exacerbate any skin problems.  That was not my experience.

[mremeet]

Thanks for the kind words nygirl and mike. I deeply depended on this place during my treatment and everyone here helped me learn and get through my treatment. That's what this place is all about, and thank god it was here to help me through. And it's not always easy for everyone to get along while being on these drugs and going through these side effects. Basically I entered into a period of temporary insanity and I got so wrapped up into my own world and my desperate attempt to kill this farking virus once and for all. Anyway, apologies for any harsh words said in the past. The whole experience seems like a long ago dark dream already. I hope more and more people get treated successfully and come out on the other side like we all did.

Andiamo when you say "The standard thinking is that the combo of interferon and ribaviron will exacerbate any skin problems." I believe this is generally true, except I would change the "will" in your statement to a "may." Of course it is a general statement and it will not apply to everyone, but generally I believe it is true. On the upside, I think if Tx does exacerbate an existing condition during treatment, it usually will not leave a lasting effect after treatment ends. One thing's for sure, IFN, Ribavirin and Telaprevir are all powerful drugs and they can make your body do bad things, especially in regards to your skin.

And Javi you ask about the solumedrol. I'm not a doctor, but to my knowledge solumedrol is a drug that is only used in rather extreme circumstances when no other choice exists. Like in the situation I was in or if memory serves Mike Simon also received it to deal with organ rejection issues pertaining to his liver transplant (correct me if I'm wrong mike). As previously stated, prednisone and solumedrol are immunosuppressants. Immunosuppressants, as its name implies, suppresses your immune system and if not used judiciously they can make you vulnerable to infections and other serious health problems. And you also do not want to take them during treatment because the whole point of treatment is to boost your immune system into overdrive for the purpose of driving the virus from your body once and for all. Taking solumedrol and prednisone will counteract the immune system boosting effects of IFN and possibly ribavirin, which are essential for achieving SVR.  Good luck with your treatment.

[Andiamo1]

Great to see you back.  I am here intermittently, but this time got involved in some heated discussions about Vertex.  I do agree with what you said.

[coeric]

mremeet - definitely a hero's journey if i ever heard one.  i've seen folks bouncing off walls on big doses of prednisone, but not on top of three hcv tx drugs!  thank you for coming back and sharing.  i recall a story about someone tasting the tela pill in order to insure they were getting the real thing - wondering if that was you?

andiamo1 - part of my interest in a lead-in is sort of like sticking my toe in the pool to check the water temp before i jump in.  let's see how this naive responds to interferon/riba before jumping into the deep end with the PI.  i appreciate your advice to jump into the deep end and get on with it.  certainly enduring any more time with interferon and riba on board does not make much sense.   i know that in order to replicate the trials i would need to stick to the 24 weeks of 48 weeks after adding the PI.  

willing -  interesting that only 38% on the placebo went to SVR in the sprint2 trials.  makes me wonder if these trials can be compared strictly on the numbers.  your point to concentrate on confidence intervals is well taken.  thanks so much for the links.  i will definitely take a closer look at the briefing docs.

thanks everyone

eric

[willing]

thanks for a great and vivid summary - the description of the crowd parting as you approached the emergency room desk makes an impression! After that ordeal I'm sure glad it worked for you - would you consider tela again if it hadn't? Per her post above, josiejo also required hospitalization but got no svr at the end. Similarly for dointime, more riba may well have made a difference in tx outcome but would not have made the rash any easier to handle.

One option that will be available after approval will be to switch to boce if the rash proves excessive thus avoiding any decrease in PI pressure on the virus. From your description it sounds as if things can get out of hand pretty fast - so for the transition to work smoothly  a patient would have to do some prior planning.

[Willy50]

This is an interesting read and as happens....so many points end up getting made that it becomes difficult to respond to them all, but a few things that come to mind.....

Re the "rash", it could be that Vertex was able to slightly improve their rash management program, or their understanding of it.
    There could be some genetic markers or predispositions for it.  (but I've read nothing yet)
    Improved Rash management programs lowered the drop out rate, thus increasing SVR.
    I theorize that increasing lead in time could also increase the incidents of rash.  As it sits some people may start and finish the 12 week triple therapy phase and cease TVR.  Adding another 4 weeks of TVR could also increase the incidence of rashes.
------------------------------------

When i was in a trial, for all of a week before I dropped out w/o dosing it seemed to me that one of the objective of a trial is to gather data.  Maybe ya'll can figure that some doctors want to "cure" people and therefore select the ones they figure have the best chance.  Others might suggest that some doctors may select the sick ones who really need the help; those damaged the most.  One thing i might add to the mix is that the drug pipeline is also a money & information pipeline for those who run the trials.  What they are really doing is mining data.  I feel that one of the objectives is to select those people who are most likely to start and stay on the trial.  The people running the trial probably have a long checklist of objectives.... a punch list of duties, labs, doses, stats they must acquire from each patient.  Each one of these also triggers a payment to the doctor/clinic.
I don't mean to suggest that it's all about money, since I think that they are doing tremendous work, groundbreaking work.  I just think that if given the choice of them in effect betting on a finisher, they will tend to select those who will go for the full ride.

If I recall there were several early TVR trial participants that dropped out early; one after only one dose.  It messes up the numbers, looks bad and then they have to start all over, which is more work for them.  The numbers cut both ways in this subject; dropouts had the connotation of being failures.  In reality, many of the dropouts attained an SVR.  Just like Trish's drug trial; tell any of the people who SVR'ed that their drug failed.  My point is that numbers can only tell so much of the story....

RE willing; I think you may have a point about muddy stats, but when you put it in the context of other trials, look at all the pegasys and pegintron studies, my God.... they are still looking and finding superiorities over one another.  There is a large amount of statistical obfuscation which occurs, in trial design, in running the trials and in the *presentation* of the numbers.  Over all, Vertex ran very clean trials and without other rescue drugs that served to inflate their response and SVR rate.  Further, they have very inclusive trials and if memory serves held one of the more definitive null responder trials to achieve better data on that subject; more so than their competitor.

Also..... not fair or objective clamoring about the other timing of trials for HIV/coinfection.  I believe it is the standard order that such studies are held.  These type trials are done at the end near approval, not on the front end of trials.  FWIW they were doing trials in 2008 which laid groundwork the trials in question;
http://clinicaltrials.gov/ct2/show/NCT00775125?term=telaprevir%2C+HIV&rank=5

Looks to me as though some of the resistance issues may even be nearly mute.  Have there not been studies which have shown that the mutation resistant variants revert back to wild type after about 2 years?  IE; if 100 people treat, 70% SVR you may be left with 30 people w/ resistant variants.  After 2 years these same people may no longer have those resistant variants and may try again, or try with some other additional adjunct ( a lead in, an add on like alinia or a new protease/polymerase inhibitor, quad therapy etc.

I'm not sure that you can make the case that these 30 people who initially fail out of the running for SVR.  It looks to me as though it is still an acceptable gamble.

best,
Willy

[spectda]

Thank you for your extremely well written and vivid post. I felt like I was scratching my eyebrows off with you as I read!

Congrats on your SVR and incredible perseverance. It reminds me that I had little to complain about in comparison, although my boceprevir experience was no bed of roses.
Take Care,
Dave

[mremeet]

Coeric - Yes I'm the one that was tasting the pills and attempting to determine if I was on placebo or not. Actually it was three of us, and then we were also requesting other taste comparisons with other Prove 1 trial participants we met online here. Of course all of this was strictly against trial protocol rules, but desperate people will do desperate things. ;-)  In the end we determined the true telaprevir pills had a very bitter, nasty metallic like taste to them. The pills dissolved very quickly and easily as soon as they were moistened with saliva. The placebos were usually described as a neutral, slightly sweetish taste. The only exception we had was one person who thought the real telaprevir pills tasted like placebos (we thought he was a Vertex plant at the time hehe). But some people have a very bland sense of taste (especially smokers, which this person was) and taste interpretations are subjective for this reason. Vertex and our trial doctors were monitoring our comments and discussion on this forum and they mentioned it us during our doctor visitations. So we kept our communications about this subject private afterwards, especially after also getting offstudy PCR's at 3 weeks to see if we were UND, which would strongly imply being on the real thing. If we were caught we might have been kicked out of the trial so we did it covertly (other than prettydamscared blurting it out here and almost blowing her cover). Anyway, seems silly now but at the time it was of paramount importance. It was a game for sure and a game I was determined to win.

willing - Thanks for the kind words, good to see you're still helping people out here. Yeah, dointime would have been helped with more riba, but as I recall her problem was caused by NO riba. She was randomized into the no riba group. Her viral decay was rapid initially, as it approached UND it started sloping off after a few weeks and then she went UND off and on for a week or two and then it came back (from my fragmented memory anyway). The antiviral kinetics for IFN and TPVR alone to me looked like a damped, prolonged version of the TPVR by itself (i.e. very rapid initial decay first 2 weeks --> 3-4 weeks approach UND asymptotically ---> float in and out of UND at low levels for a week or two--> maintain HCV+ status at low viral load thereafter. I don't recall if she got riba later, but I think she did after treating again. But by then the TPVR was useless, she had TPVR resistant strain and that ruined the whole thing. You only have one chance to get it right, although I still think dosing with another PI especially after pre-treating with IFN riba for 4 weeks prior might work well. I hope is she reads this she will comment and let me know how she’s been doing. I miss her and wish her well.

As far as my rash goes, it did get out of hand, but only because a comedy of errors ensued as a result of no prior side effect knowledge base for TPVR at that time. The one thing I hope newbies who are considering treatment consider is that although my story is awful, it's only awful because the rash was totally mismanaged. It doesn't have to be that way AT ALL for any new person considering treatment. Basically an analogy of what happened to me is the following: I wasn’t allergic to poison ivy at first. So I rolled around in poison ivy for about 5 weeks until all of a sudden - I developed an allergy to it. Then I took internal medicine (prednisone) to thwart my body’s natural reaction to this new allergy. But instead of staying clear of the poison ivy, I continued to roll around in poison ivy over and over again every day while I was taking less and less prednisone. Eventually the prednisone suppressive dose reached its critical limit (about 10mg for both me and prettydamscared), and then the bill came due for all the rolling around in poison ivy after developing (and artificially suppressing) my newfound allergy. Obviously the right thing to do is once you develop that allergy, is DUH – stay away from the poison ivy!

So again the thing that's important to remember is that the skin allergy that is developed for TPVR in the people who get it is just that - it’s DEVELOPED.  It usually does not manifest itself immediately. It takes time for your body to develop an allergy to it. From what I saw the typical "time to allergy" for those susceptible to it was about 5 weeks (give or take a week). That's about what it was for me and prettydamscared and a few others I heard about through the grapevine. I did hear of rare cases of some who reacted badly to TPVR on their very first dose, but they were very rare. Most who got the bad rash only did so after about a month of treatment first.

As an aside basically this situation is similar to other skin allergies I’ve heard about. For instance, I knew a guy that used to work with epoxy resins used in custom built aircraft. He would mix these resins and use them to coat Kevlar and carbon fiber sheets wrapped around foam cores. During this work his skin was exposed to the epoxy. Even when he used gloves, he would inevitably get some on his skin. For a few years he didn’t really have a problem, but then eventually it caught up with him. He then rather suddenly developed severe rashes if he came into contact with the epoxy. From then on he no longer could come anywhere near the stuff or he would break out into hives. I’ve heard of other situations like this, where a person who had no allergy to a particular something or other, would then later develop an allergy to that same substance over time (and occasionally the reverse of this phenom could occur as well).

Also, and this is something I’ve never mentioned here before, but prettydamscared had a few VX-950 pills left after she had developed her allergy and went through her “prednisone event.” She had stopped the VX950 well before and her rash was under control, but she decided to not “waste” the few pills she had left (and it was also against trial protocol to take anymore pills, all unused meds were to be turned in). I told her not to do it, that it would cause the rash to come back with a fury. She agreed and said she wouldn’t – but she secretly did anyway. Of course the rash came back with a vengeance and she almost crashed and burned just like me. She wasn’t thinking clearly at this time and it was a big mistake. One that almost terminated her entire treatment.  

Anyway, so what this means is that Telaprevir still offers a MASSIVE edge to even those people who are vulnerable to developing a bad rash like me. Knowing what I know today, I would have absolutely used TPVR if I had to do it all over again (and I was treatment naive again). Except this time I probably would have started my treatment with SOC without the TPVR first. Go maybe 2-3 weeks into treatment with the SOC and get those molecules into the system and get the immune response ramped up and clicking. Get the viral load down and my system primed.  Then I would have introduced the TPVR at week 3 or 4. By that time the virus is already on the run, and knowing that I had about 5 weeks of utility from the TPVR before the itchy/scratchies set in. Stop the TPVR when the rash started up (probably around week 10 or so), continue with SOC for a total of 24 weeks and then call it quits. I think that would be pretty optimal in terms of the SVR % success rate/time of treatment/minimal side effect profile.

Specta – Hey, I’m sure boceprevir has its own place in Dantes inferno. From what I recall its main torment was “gastro issues.” I can only imagine what that means in real side effects. But Montezuma’s revenge with a garden hose up your butt comes to mind ;-) . Another little publicized (but VERY common) side effect of TPVR was “anal itching.” Out of self humility I won’t go into anymore details, but it wasn’t only my eyebrows that got scratched off. ;-)

[lapis]

Ah, so you're one of those who came before me and paved the way!!  A little birdie suggested I might taste my meds so...I also tasted my TPVR tabs and could definitely tell the difference at wk 9 when I was switched to placebo.  I was a little worried when I realized I was on the placebo but hey, it worked.  For me the anal issues started on day 3 when I forgot to take the dose with a snack and wound up taking it on an empty stomach, OMG, rapid response in the GI tract!!!  The itching was strange but the burning is what I remember.  And that continued pretty much until after the 8 wk mark when the placebo replaced the TPVR.  Still, all worth it.  So that's another caution for future tx'ers, I think, be sure to take the med with a snack.

As others have said, thanks so much for telling your story.  And good to "meet" you.

Lapis

[FullOfHope77]

Hi Andy, its been a while since I've been around and forgot the name of the site and had to search for a while and then what was my login... crazy but I found it and you're one of the reasons why as I enjoyed greatly your posts a few years ago when things were 'dark'... we're here Telparivir is approved we're successful guinea's and others will now benefit. I wanted to say hi and will go back and read all the posts later! The Best!
Scott