rescue drugs and trials

Earlier this week, I had a message from the research coordinator that my Hgb had dropped to 9.5 and that I should decrease Riba to 800 mg per day.  I have done that and withing two days I am out of bed and taking short walks -- on level ground - LOL.

The bad news here is that I have increased the probability of relapse by lowering one of the important drugs.

I once posted that I thought rescue drugs were banned in the trial strictly based on the cost to Vertex, and many people disagreed.  I still believe that is the case: the purpose of the trial is to determine how the trial drug will perform in the environment in which it will be used; clearly, procrit will be part of the environment once the FDA approves the drug.

Vertex has given the trial participants a long list of drugs that interact with Telepravir and should not be taken; Procrit is not on the list.  I know people want a pure environment, but there is no such thing.  We humans live in a polluted environment and we take many other drugs, so why pick on Procrit?

I think the answer is money: Procrit is so expensive that Vertex would have no choice but to provide it to trial participants in order to have a level playing field.  If they did not do that, people with good health insurance would get the drug, rich people would pay out of their pocket and poor people would not get the drug.  This would not fly with the FDA, since the trial is biased against poor unemployed people.

I am curious about what you all think.

[zazza]

If Telepravir is approved, it will be used by hep C patients all over the world. I live in Sweden, and here rescue drugs are only prescribed for people on chemo therapy for cancer, not for hep C patients on tx. Isn't this one possible reason why rescue drugs are not allowed in trials? They need to know how well tx with Telepravir functions without the use of rescue drugs.

Curious also, did they lower your riba just after one low reading of 9.5 of hgb?

[ladywhy]

I know of someone in the trial take procrit on their own. They knew it was their only hope to stay in. She is still in the trial though they are not aware of her taking the rescue med.  'nough said.

[Andiamo1]

I don't think so. Insurance companies here will usually pay for Procrit for hep C patients.  Mine did in a previous treatment.   Vertex can approach J&J and ask them to participate in the trial and then Procrit would be approved for hep C patients.

My Hgb dropped quickly to 10.3 and then slowly to 9.5 over 20 weeks.  It reached the point where I could not function.

[jmjm530]

It's not money. There is so much money at stake here, that the money spent on Procrit during the trials would be a drop in the bucket compared to what Vertex could make with better results using rescue drugs. It probably has to do with FDA protocols or something similar.

-- Jim

[Andiamo1]

I could do that if I can find a doctor to prescribe it.  I have tried to stay withing the trial rules and I plan to stick to that, although I am not sure why.
Eric

[Andiamo1]

In the last financial quarter, it looked like the trials were costing much more than Vertex originally forecast and they would have to go out for more money.  The stock took a major hit when that happened.

The issue is not revenue once FDA approval is given, it's cash flow while they are in the approval process - a very different issue.  I can tell you from personal experience, companies pay dearly when they underestimate costs and need to go  back to the well.

Eric

[jmjm530]

The reason to stay within the rules with pertinent compliance is so that the data collected will not be corrupt for future patients.

For example, let's say you figured out you were in the non-riba arm of the trial and you found a source for riba. You took the riba along with Teleprevir and then became SVR. The non-riba data is now corrupted and slant the results in a way that may not be accurate if someone actually did not take the ribavirin. Of course, if you disclosed the fact that you took riba after the trial, your data would be thrown out. The trial coordinator probably would be pissed off -- given their investment in you -- but the data would not be corrupted. And indeed it may be used in some way, even if anecdotal.

Taking Procrit on the other hand, does not directly affect SVR, but might indirectly affect it by increasing riba compliance. If you're already near the 24-week mark, not sure how much difference it would make since I can't see the reason to treat longer than 24 weeks on the full protocol. But personally, if I did feel it would make a significant difference, I'd consider Procrit and then tell my doc after the fact, risking both his wrath and whatever other risks involved in taking a drug without formal medical evaluation.

-- Jim

[jmjm530]

I think Vertex would hand out Gold Rolex watches if they felt it would increase SVR and/or decrease sides, etc. That much money is at stake if this drug becomes the magic bullet we all want, or something close. I just don't see them skimping on epo for financial reasons. I believe it has to do with following set protocols for approval and in order to do this I believe they have to play with the same rules that SOC does so apples can be compared to apples.

-- Jim

[Andiamo1]

I certainly agree with what you say here.  I am just trying to make procrit part of the trial.  I am sure J&J would be agreeable to participating and both drugs will show their stuff in a better light due to the greater compliance and the increased comfort of the patients.

As for me personally, I think you are right about the 24 weeks.  My issue with stopping ,if I end up the the 48 week arm, is how I will feel if I relapse without doing everything possible to beat this.  I probably will not get another chance given my age.

Eric

[jmjm530]

As to epo, again I think it has to do with FDA approval. Vertex has to show Teleprevir at least equals SOC or better and the SOC trials did not use Procrit.

As to 24 versus 48 weeks. If it were me, I'd look at whatever data was available at decision time. Preliminary results appear to show that 24 weeks is the magic number and I believe that has been Vertex's target all along. Hopefully more definitive data will be in soon. Personally, if after studying all trial data I came to the conclusion that 24 weeks was the number, I'd have no problem stopping regardless of which arm I was in.

That said, the data coming in is from treatment naive's which may or may not translate into someone who has treated before. Also, how your're handling sides must be factored in. Not an easy choice.

-- Jim

[Andiamo1]

I don't know if you have ever dealt with venture capitalists, but they are sharks of the first order.  Every time you go back to the well, they take a larger piece of the company and all your hard work goes to them instead of to you.  Vertex is already over budget on Telepravir and the increased cost of procrit would put them over the top.  It would be nice if startup companies could deal with real product issues instead of financial ****, but that is the real world.

Someday if you have any interest, I can relay a first had story of how a great product can end up in the gutter due to the financial issues related to bank covenants and stockholder agreements.

I guarantee you that the management of Vertex will do anything possible to avoid giving up more of the company.  I think they will present the statistics in a way that minimizes the drop out rate due to anemia and talk about how that will improve once approval is given.

[Andiamo1]

I am going to try and hang in until the AASLD conference in November and see what data is presented.

Thanks for your input on this.  I appreciate it.

Eric

[cruelworld]

the way i see it, this is your last realistic shot at this. do anything and everything
you have to do to win. youve got it whipped this time if you stay on track dosage wise. dont risk it.
this is life or death for you, the fact that you are a trial participant is relatively meaningless is this context. an experiment in pain is somewhat tolerable but
reduced dosage as far as you have come is unacceptable. i find myself in the same spot of low hemo yet my doc wont give my any EPO! im hovering around 10 and below. he says its not low enough so i will try to get used to it. of course he suggested lowering the riba and of course i said no. i am sending my records to other docs presently. you can find a doctor that will do it, it may not be easy but you will. no one on the face of this earth could ever fault you for that decision.
dont let them corner you.

[ladywhy]

Don't give up hope just yet...

[Andiamo1]

I am going back to the full dose at the end of this week even if it means I stay in bed until the 24 week mark.

That is sound advice you give me.
Eric

[Andiamo1]

I have not given up hope and I will stick it out.  I remain optimistic, but confused about some of these issues.
As always, thanks for you support and plan the sail date when we reach SVR.  I hope you are well.
Eric

[Tippyclubb]

I once posted I thought rescue drugs were banned in the trial strictly based on the cost to Vertex, and many people disagree.

I agree and heres why.  They wanted me to participate in a Taribavirin clinical trial and when I asked about rescue drugs I was told yes they could be taken, but they would not cover the cost.  I had to pay through my insurance or out of pocket.

Tippy

[FlGuy]

Here's a coincidence:

http://www.vrtx.com/Pressreleases2006/pr063006.html

[Andiamo1]

Interesting link; now I am really puzzled why they didn't get J&J to participate with Procrit.

[FlGuy]

Since JNJ has a real interest in the success of the trials and they are providing a lot of funding to vrtx, I assume that the exclusion of rescue drugs is for another reason(s).  And, I'd guess it's to evaluate the profile of the drug on a consistent playing field across the arms.  It is, after all, a trial.

[Andiamo1]

I have to agree that there must be another reason, but drug evaluation can't be one of them.  

Why procrit and no other drug?  Yes it is a trial, but no other drug is excluded for no reason, so why procrit?  I could easily understand if it was on the contra - indicated drug list, but it is not.  So aside from 20 or so drugs that can produce dangerous interactions, I can take any drug I please except procrit.

I am sure there is a reason, but it sure escapes me.  The only thing that jumps out about procrit is the enormous cost.

[Willy50]

Eric, This is kind of a sad thread given it may have been the last post by PDS.  I included some information that may be useful to you about possibly fighting anemia without procrit.  It's useful to anyone treating I think.

http://www.medhelp.org/posts/show/93377

You have other questions and here is my take on those.  You know how as the trials go on there are little changes in the way they word things?  I don't expressly know what is allowed or disallowed now.  I believe in the perfect world they wanted no one to take any rescue drugs.  With each drug you add you increase the likelihood of drug interactions.  What if....for instance a painkiller or some other drug was hepatoxic?  How would they be able to discern whether the trial drug caused the elevated LFT's or the painkiller?  In the scenario that interferon caused suicidal ideation...... how would one pick up on that if a patient was on antidepressants?  So anyway....... excluding rescue drugs keeps things simple and may keep the results more valid.

What do they allow?  I have no idea.  I know that IF people were doing XYZ rescue drugs this forum would be a poor place to advertise it, at least unless one wanted to announce it publically.  I think it's such that people are afraid to even talk about it.  They don't want to get in trouble in any way.  I don't have a hand out on what is allowed, what is forbidden, what is grey area...... but have gotten the impression that different hospitals, possibly different "takes" on what is allowed.  I don't really know if that's true however.  People either don't "hear" things the same and they don't always report accurately either.

IF I was in the trial and needed the drug I might be tempted to spring for it; particularly in the first 6 weeks to keep me on full dosage.  Whats $5000 dollars if your treatment is free and if staying on full dosage nets you an SVR?  In the link I provided not only is there information on how to help fight anemia naturally but also a mention that both neupogen and procrit also have free drug programs for those who may need the drug but cannot afford it.  In some cases, it's the people WITH insurance who can't afford it.  The people with NO insurance qualify for the program and may get the drugs free.   : )

Speaking of investing; once the Vertex gets approved the sales of procrit might also take off.  :  )
Also on this topic be aware that these drugs are not without some side effects of their own.

Eric, I also agree that the critical part of the trial has probably long since passed.  Cutting back on ribiviren in say the first 8 weeks would seem to be the more critical period.  We won't know until the results are released......and it will be a WHILE till the Prove 3 data is released.  I don't think one should directly infer that the Prove 3's will have the same success rate as the Prove 1's and 2's.  In any case, you won't hear about those till AASLD anyhow, some 6 weeks off.

I'm very excited to hear how you and the other Prove 3's do at the 24 week mark.  Yes.....stay in bed if you have to.  Full dosage may be important, particularly for the Prove 3 treatment failures given that may already have some resistance issues.  The amount of time you have on the trial is finite and if you can just keep up the resolve a bit longer you will know that you did everything as well as you could; no regrets.

best,
willy

[ladywhy]

Here's Bug's e-mail address. She is waiting for you to make contact
***@****

[ladywhy]

Here is mine: ***@**** it down quick before it get's deleted

[ladywhy]

ybonfield at earthlink dot net

[Andiamo1]

Those of us in prove 3 have been given a detailed paper on drugs to avoid, and those that can be used with caution.  Procrit is not mentioned in this list and it and Nupogen are the only drugs that are specifically forbidden under any circumstances.  This is not up to the administering medical center, it is part of the agreement with Vertex.

The only thing that is obviously in common between these two drugs is the high cost.

The coordinator told me that it is not that critical if I need to reduce the Riba dose at this  point.  She said that I am saturated now and a couple of weeks at a reduced dose will not be that critical.  I believe that no one can know that for sure and I don't want to take any chances.

thanks again for all the data and support.

Eric

[dointime]

Remember that you will have more information on how your virus is responding to tx when you get your VL results at the unblinding.  The earlier you went UND and stayed that way, the better your outlook for SVR.      
dt.    

[jmjm530]

I think you're making my case in your above post. If you were to get Procrit outside of the study -- such as the other drugs approved on the list -- Vertex would not be paying for those drugs. They would be either paid by your insurance company or out of pocket.

In this light -- and others -- the  fact that Vertex specifically forbids Procrit and Neupogen, again leads me to believe that it has nothing to do with money but the way the trial was set up for FDA approval. Again, Vertex has to show that their drug combo at least equals or is better than SOC. The SOC FDA trials did not have those helper drugs. Another reason -- or perhaps related --  may have to do with getting a better handle on the side effect profile of these newer drugs.

I'm sure you will see follow-up trials allowing more liberal use of both Procrit and Neupogen.

[Andiamo1]

The link provided by flguy convinced me that it isn't money, since Vertex has partnered with J&J and they make procrit.

I participated in the phase III trial for peg and riba.  It allowed Procrit.  Since Telepravir itself adds to anemia, the FDA might have made them keep it out in order to see the total riba/vx impact on Hgb.  It will be interesting if they allow it in phase III.

In the post to you about money I was trying to explain the way VCs and banks prevent you from spending money even when the ultimate prize is many billion dollars, sometimes in ways that make no business sense at all.  I was surmising that this might be the reason.

Eric

[NYgirl]

Please hang in there.  Once the virus is killed off it's killed off and if you were SVR at the time of the decrease it shouldn't matter that you did decrease.

I've never thought it was right that trial participants aren't allowed to take Procrit - especially if the insurance company will pay for it - but I do believe that Jim is right in this case, it's not just the money.  It is still in the "trial" stage.  When it is approved by the FDA and becomes a SOC drug - then there won't be any problem allowing the different rescue drugs because it will be out of the trial environment.  

I'm sorry your hemo dropped so low - many of us know what that feels like.  Lately I feel for some reason like I am very anemic...same exact signs and symptoms...but Im not on any meds so it's confusing.  But it reminded me how totally much it SUCKS and my heart breaks for you trying so hard and having to feel SO weak.

You are so lucky to have Mafalda there to love you and give you strength.  She must be a constant source of compassion, you are blessed.

Your friend, Debby

[APKhaos]

We should have a few beers and share VC war stories one day, ideally leaning against the pushpit on a nice broad reach :-).

FWIW, my HGB dropped from 15.9 to 10.1 in quick time, and bounced along the bottom between 9.8 and 10.low for the remainder of tx in Prove 1. Whenever it turned up <10.0, the trial coordinator called me in for a second CBC to confirm before dropping the Riba dosage. In every case, my HGB clawed its way back to a flat 10.0, so no Riba reduction. You should ask you clinic to do a second CBC before accepting the riba reduction. Also, there were other P1 lab rats who were given a Riba reduction but still achieved SVR, so all is not lost.

Also FWIW, there was absolutely no change in my HGB between the first 12 weeks of SOC + Telaprevir and the second 12 weeks of SOC only.

[Andiamo1]

Are you in the NY area?  Perhaps if I reach SVR I can drink again!

I am in week 22 now and don't have another blood test until week 24.  I am going to raise the Riba dose back up to 1200 tomorrow.  I have more than enough drug to carry me until the next trip to the research coordinator.

Are you involved in a startup?  It was certainly an eye opener for me to see the negative impact banks and VCs can have on your business.  It is like doing business with the devil.

[APKhaos]

I'm in the DC area. Even though I'm SVR, my drinking is extremely moderate.

I've led a couple of startups, and now I'm on the boards of several. There are major bear traps to be avoided as a startup. Having BTDT makes it possible for me to help these companies navigate their way through without falling into them. The scars of battle are vaulable after all.

[geterdone]

I have a question, do you feel better since reducing the dosage of Riba from 1200mg to 1000mg? I ask this because I did just that six weeks ago, reduced the riba to 1000mg and it took about a week and a half to start feeling normal, well as close to it a possible. I had set a date to increase it back up to 1200mg next week and have a doc’s appointment next Wed. I had gotten a letter from the doc that said my enzymes are in the normal range and blood count is 42.3 and am happy about that but he did not send the lab work and will find out on the next visit. I am hoping that the ths are also back in the normal range as well and will confirm that it has bounced back. I hope what ever you decide is good for you.

jasper

[Andiamo1]

I feel much better.  I was only getting out of bed a few hours a day and now I am up most of the day.  I can take slow walks and enjoy it.  Not running any marathons, but definitely feeling better.

My starting Hgb was over 16 and last week was 9.5.

Eric

[Andiamo1]

Hypothetically, you are the manager of vertex; what advantage is it to the company to ban rescue drugs?

Does that make the trial scientifically more accurate? If so, why just these two drugs that have nothing in common except high cost?

Level the field (what ever that means)?

Why not ban topical cream that treats the Vertex rash (it uses steroids and could influence the immune response)?

Why is it bad to include J&J in the trial and end up with approval for treating HCV with Procrit and increase the SVR rate with better compliance?

I don't have the answers, but nothing anyone has said provides a logical explanation IMHO.

[Andiamo1]

and by the way, procrit was not banned in the earlier trials - I took it in the phase III pegasys trial.

[Willy50]

Let me start by saying I know nothing.  : )

I think the issue is about clearly evaluating the compound.  I don't know how much say Vertex has in trial design.  Maybe lots or maybe they follow what the FDA recommends.

It may be that for drugs that are already approved the FDA won't insist on certain protocols.  In this case however Telaprevir hasn't gone through umpteen trials; this is the first time thru the blocks.

I think this could be about statistical certainty.  Think of a few classes you've had in school.  A class where everyone passes with A's and B's does not really have the tests set up well; likewise with a class in which all flunk.  If the tests the grading is set up well in the end there will be a spread of results.  

You are correct that if all rescue drugs were permitted that there would be some sense of how effective the treatment was.  The point of the trial however is to gain as much clarity about the exact efficacy and exact toxicity of the compound when taken in certain doses with (perhaps in this case) interferon and ribiviren.  Each drug and compound added to the mix tends to muddy the meaning of the results.  The results are the actual purpose of the trial.  Curing people along the way is a happy byproduct of the testing.  Restated then, they could cure more people but the results and meanings of the trials would be less clear.  

It may be that in Phase 3 other new changes may come into play.  The use of rescue drugs could become one of them if sufficient information has already been gathered.  That will be up to the FDA and Vertex.  You are correct that information can be gleaned either way.  I'm simply guessing that if for instance you were trying to discern; does TVR cause anemia...... the use of procrit would muddy the meanings of a trial.  

A final point to make is that if you google any of the rescue drugs you'll see that they can all provide their laundry list of symptoms.  (remember the black box warnings for TX; it's endless  : ) )

The FDA not only has to track the trials and ongoing symptoms but any complaints which can arise FOLLOWING the trials.  If you are an FDA official you have to be concerned about what happens about both.  

By the way..... have you noticed how many threads there are about anemia right now?  It's a very common ailment in people who treat.

APK, interesting to read about your background.  We are a diverse group.

best,
Willy

[Andiamo1]

I am going to give up on this, since I must be very inarticulate not to be able to describe a simple problem.

But I can't resist one last try:  Evaluating the compound can't be the reason these drugs are not allowed.  They are singled out over all other drugs.  Many drugs are advised not to be used, since they interfere with evaluating the compound; systemic steroids for example.  There is a long list of these drugs and procrit and neupogen are not on the list.

Again, these two drugs are unrelated chemically, so why these two?  the only thing they have in common is price.

The FDA does not dictate the details of the trial.  They only look to see if it is structured in a way to give an accurate picture of how the drug will perform in the real world.  Since Procrit and Neupogen will be used after FDA approval there is no reason to exclude them from the trial.  I participated in the earlier trials of Pegasys, and Procrit was allowed; I took it!

[Andiamo1]

[Andiamo1]

I hope that last comment didn't sound cross.  I appreciate that you took the time to think about the issues.  My problem is TX and lack of sleep, so that I feel very inarticulate these days.  

It feels to me that I am speaking a different language than everyone else. I spent a lot of my career managing whacked out computer scientists and mediating design disputes over topics much more complex than this, yet I can't influence any thinking on this topic.

I think that I can easily be wrong on this and Flguy provided a link that made me believe that part of my theory was wrong.  But no one addresses the main issue of why these two drugs are treated separately from ALL  other drugs.

[geterdone]

After reading the thread I understand what you’re saying about the two rescue drugs. It has nothing to do with the trial directly or FDA at this point, it is business and a marketing thing right now. The vx telepravir has to stand on its own right now to find the lowest possible tolerance and it seems that the hemoglobin is one of the stumbling blocks at this point of the trial phases. The people in the trial will suffer the most because of it but after the approval of telepravir, if it should happen, I am sure these two will be the rescue drugs of choice. Just my take on the thread.

jasper
  
LOL... different language

[Andiamo1]

Whew!!!!!!!!!!!!  THANK YOU.

[Willy50]

[Willy50]

Whoops, hit the wrong key and it "sent".  I'm off to work but no worries you came across fine.  

Willy

[geterdone]

Startups are very had even with the best product on the block. For a distraction, read up on this company in your spare time, hehehe, no pun intended. Opsware Inc. great story and will be for some time to come but it all came down to marketing and networking.

jasper

[APKhaos]

This whole discussion seems to be ignoring the possibility that HGB drop is entirely due to SOC drugs, particularly Riba. As I said above, my HGB dropped rapidly after starting SOC + VX-950 and bounced along between 9.8 and 10.2 the entire 24 weeks of treatment. The last 12 weeks were SOC ONLY. Stopping VX-950 at 12 weeks had absolutely no impact of HGB levels. In fact, they tended lower in teh last 12 weeks WITHOUT VX-950. That's just one sample, but the point is obvious.

As for the 'no rescue drugs' trial design, the anwer probably lies in keeping the trial data free of potential interactions caused by additional drugs. Its flat out not fair to the subjects, and anyone in Andiamo's position has every right to be pi$$ed, but I suspect its nothing more sinister than protecting the integrity of the trial data.

[Andiamo1]

Interesting - this was the last product I built for Broadview Networks.  My partner did the provisioning and network management and I did the billing system.

[sfbaygirl]

I always had a problem with no rescue drugs on the trials, wouldn't do it knowing this is the case. As a relapser, I KNOW I needed them on tx, and wouldn't expect the next tx to be different. I agree with those who say 'it's your body and you should look after yourself'.  Yes, I know it's going to skew the data for the trial, but it were me and I needed a rescue drug to finish tx after many, many weeks of hell, I would find a hemotologist to give them to me.  Boosting blood counts doesn't have an effect on the VX.  Perhaps it's dishonest, but frankly it's my body, my tx and potential SVR. Why put yourself through this only to have to quit b/c the trial won't allow rescue drugs?  My life, my chance at SVR.  I know others have done this on trials....okay maybe I'm bad,  but that is the main reason I doubt I will go into a trial.  

[Andiamo1]

I agree with you and if this had happened early in treatment, I would probably have found a source of Procrit.  As it is, I am at week 23 now, so I will tough it out until I can have procrit.

In this trial, you run the risk of Vertex discovering that you took it and bouncing you out.  I am sure the change in Hgb levels would get their attention.