My Appointment with my HepC doc

[dointime]

MY hepC doc is a virology consultant.  He's been on the front line of the HIV and HCV wars from the beginning, so he's been kicking viral @ss for a long time and I value his experience, especially with the HIV combos and resistance.  Anyway it is lucky that I don't want to do the triple, because he told me at my appointment a few weeks ago that even if I did want to he would not prescribe it for me because:

a) the composition of my current viral population is unknown following my tx in a trial with tela.
b) not enough is known currently about retreatment with a PI.
c) my ifn response is sub-optimal, based on my having a breakthrough with my previous SOC tx.
d) my liver damage is not severe.      

None of the above came as a surprise or bothered me because my planA has been to wait for a non-ifn combo to be approved.  However what he told me next did bother me.  He said that there might be 'issues' with the cost of the drugs for the new combos.  It might be that some people will get the drugs and some will not.  Read that as - a person of my age (61 now), not seriously ill, with no dependents, might go to the back of the queue.  This is socialized medicine in the UK which up until now I have been very happy with, but I am not liking the sound of this at all.  Anyway, it is early days and the drugs are not even approved yet, so nothing is set in stone.  But I have to pay attention to this heads-up.  

So - ironically - after advocating to wait for approval, I might find myself having to scramble for a trial that will take me, to get the drugs paid for.  This after paying through the nose all my life into the health service.  In the US that would be called Fraud.  I'm still going to wait, however, for the phase 3 trials to come around and then see what I'm even eligible for.  

dointime
------------------------------------------
For those that don't know me, I did the VX-950 Prove 2 trial, the no-riba arm in 2007.  I was UND at day 15 then had a breakthrough.  I also got a severe rash but managed to carry on till the end at week 12, not knowing about the breakthrough (it was double blind).  My viral population may have mostly reverted back to base line wild type.  Alternatively my wild type may have been completely eradicated by the VX-950 and what is currently there might be an equally fit or more fit mutated resistant strain.  Getting tested for this is on my to-do list.  

After the 12 weeks of the trial I rolled over immediately to SOC and went UND again at week6 of SOC.  I remained UND for 16 weeks and then had another breakthrough.            

    
        

[dointime]

Well, it has to be said that it is good 'patient management' to put the over 60's, not severely sick, to the back of the queue where they will most likely die of something else before getting tx and thereby not cost the health service anything.

So it's all good then.

dointime

      

[Trish77]

"So - ironically - after advocating to wait for approval, I might find myself having to scramble for a trial that will take me, to get the drugs paid for.  This after paying through the nose all my life into the health service.  In the US that would be called Fraud."

Without being flippant at all, in the U.S. they've called that patient management.  Not sure if you saw some of the articles posted just after Tela and Boce were FDA approved and just coming onto the market.  A number of hepatologists had a significant number of warehoused HCV patients and couldn't treat them all at once so they were and have been treating those in most need first.  I expect something similar when all the costs get sorted out in Canada, that the funding may be portioned and to those most in need.  Remains to be seen and I can't say I have much argument with that.  The disappointment, of course, comes to those such as yourself who have been waiting without being aware this is the way it would be when the drugs finally become available.  I suppose the consolation if there is to be one is that even better drugs are on their way and you have some options, which is more than some are able to say.  Easy to say...hard to wait when you just want this done and over with.  Hope this ends up being for the best after all for you.

Trish

[dointime]

Roche is advancing R7128 in NCT01278134 after having renamed it RO5024048 to confuse everybody.  One arm is an all-oral combo.  It is phase II but I get the impression that they do want to move on with it now that the ritonavir has solved the toxicity problems with danoprevir (formerly ITMN-191).

When I said in my post to you that " Unlike previous boring AASLD's, the one a year from now should be sensational." what I meant was that we will have results one way or the other.  The all-oral combos will either have proven themselves by then or will have fallen by the wayside.  Nobody remembers better than I do, all the hype when Vertex did the no-riba trials.  I was so glad to be selected for the no-riba arm.  I really thought I had it made with less toxicity and less sides than the other 'less fortunate' participants.  One year later we knew the dismal truth that it didn't work without riba, and 4 years later here I still am.  

As soon as one of the current combos starts showing 100% SVR for geno1 previous non-responders I am pretty sure there will be plenty willingness to get that combo on to the shelves ASAP.  I do worry however that we are falling back into recession and the lack of financing for large scale trials will restrict the speed of development.

dointime    

[willing]

dointime: thanks for the good wishes.  I certainly agree about avoiding ifn collateral damage where possible - no more 'scorched earth' than required is a wise strategy and something I may not have followed on this round.  However my experience has been that approval times can be deceptive. I relapsed  at the end of '03, didn't test for a year or so and needed to make a decision in '04 about retx. At that time it seemed obvious to me that waiting for next gen drugs was the way to go. BILN-2061 had just gotten dumped but both Vertex and Schering (now Merck) had promising drugs in the same NS3/4A class. The NS5B field was also looking promising with candidates from both Roche (R1626) and Schering. As it turned out everything fell by the way side other than boce/tela and they  didn't reach the pharmacy until last May - a seven year wait.

The BMS/PSI combo looks great - but great anti-HCV technology is abundant these days, what seems to be scarcer is a willingness to bring drugs to market. For example Roche seems to be making no move to take R7128 ( a good drug that got many here to SVR) to phase III.

Trial NCT01359644 is still a small IIa (84 pts, naive). Final data is not expected for a year. Add up the  time for a larger IIb trail, much larger phase III and a year for the regulatory process. The shortened (24w) tx time certainly helps but it's still a year before final results are in for each trial.

Meanwhile BMS790052 will have finished large(400 pt) IIb trials NCT01170962 and NCT01125189 within a year and should be ready to start phase III by Jan '13. Looks like a 1-2 year lead over no-ifn.

curiouslady1: did you notice the start date on NCT01359644? hopefully a typo!

[dointime]

Wow!  17 years.  And curiouslady1, 20 years.  We can all relate to the terror of the newly diagnosed but not so much is written about the psychological effect long term of knowing we are infected with hepC.  There's a kind of unwritten assumption that long-termers who are over the first hysteria, settle into a kind of stoic acceptance.  WRONG!  Well maybe some do but the 3 of us here in this one impromptu sampling certainly have not.  Just because we wait for what seems like eons for tx does not mean that we are complacent or have found our 'comfort zone' with it.  Ha ha.  

So coping with the psychological challenge is a major issue.  Distraction is my favorite way of dealing with it.  I 've got into a lot of things which I might never have done if I hadn't started off by seeking distraction.  Running from that black cloud has had me running to some interesting places.  When I find myself obsessing I have learned to switch channels in my head.  

susan - what a story, so interesting to find out how it happened for you.  So glad to hear that you are getting some nice down time after your latest ordeal.  I love listening to the waves too.  I think the sound resets my brainwaves, like getting a brain reboot.  You are lucky to be in a beautiful part of the world.  I will be spending some time on the west coast US this winter and looking forward to the beautiful pacific sunsets there.  

I really think that we are entering the end game now regarding medicine getting on top of the virus, just like they have done with HIV.  We just have to make it long enough to get there, and sadly some of us will not.  Anyway here's to waves and sunsets and - hey - that first glass of red wine on the beach after I get SVR is going to taste like HEAVEN!  :)
DT
                        

[susan400]

'Since my diagnosis 5 years ago it's been like having a black, cloud hanging over me that never really goes away'...

Oh-Oh-Oh, how much I can so relate to that statement, you have no idea!  I was diagnosed with the actual Hep C test in 1994; prior to that in 1985, I was told by a doctor at a walk-in clinic that my blood tests from an earlier visit, indicated that I had elevated liver enzymes and that I'd had some kind of non-A/non-B hepatitis, but to not worry about it, because it looked like to him, it was not there.  WRONG!  But, back then, they didn't even know about Hep C, so I guess ignorance is understandable.  Anyhow, he sent me on my way and didn't say anything at all about not drinking, so, guess, what?  I drank.  That is, up until I found out in 1994 that I actually had active Hepatitis C, which was confirmed with a RIBA test.  After that I still didn't treat because all they had to offer me was Intron-A a 3 x a week interferon only treatment; which my doctor told me didn't work that well.  So, I waited until Ribavirin came out and I got in on the tail end of the clinical trial for Ribavirin (Rebetol), in 1997.  So, I've had that black cloud hanging over my ever loving dirty blond head since diagnosis in 1994.... 17 yrs.     But, I actually have had some good times in between treatments, so it hasn't all been black cloud days.  Today, even though I'm still dragging butt post TX, my sister and I went out for an ice cream cone (which was chocolate and I loved it!) and then, we drove over to the beach and sat under the pavillion (since I can't get in the sun) and watched the waves, the surfers, and listened to the waves and the sea gulls and it was very nice and relaxing and helped my mood.  

Susan400

[dointime]

"  I just wonder if, even after SVR is declared, will I still have to live with the fear that I will have a breakthrough at some future point and when is a cure really a cure?  How long after treatment and clearance have there been breakthroughs anyway?"

It is extremely rare for SVR not to be durable, ie. so rare that you don't need to worry about it.  Just don't get re-infected!  

As you are discovering, the uncertainty of tx, especially in a trial like yours, is a major psychological challenge and source of stress.  If you have an active imagination and an enquiring mind then it's worse.  There's not much I can tell you to make it easier except to say that myself and others have survived it and you will too.  I know what you are saying though.  Since my diagnosis 5 years ago it's been like having a black cloud hanging over me that never really goes away.  As for the ifn, I'm with you.  I was scared the first time, but now that I know what it is I'm even more scared to do it again.

Well, as you are committed now all you can do is keep taking the pills and do your best to go one day at a time.  Cross your bridges when you come to them.  Wherever you get to, there's people here who have been there and can help.  I am so wishing that this works out for you all the way to SVR.  Good luck
DT          

[curiouslady1]

Yes, they were speaking of interferon I guess and maybe other cheaper drugs being approved first in other countries.  In any case and as you might imagine the thought of what happened to you makes my skin crawl.  In my (almost worse) nightmares the all oral regimen gives me a UND early on and then I get a breakthrough after the experiment is over and whatever resistant buggers there are become so nasty that I sail through the stages in no time and become ESLD before anything further can be done.  Actually, someone on another list told me that this is what happened to her when she was supposed to have been SVR.  I just wonder if, even after SVR is declared, will I still have to live with the fear that I will have a breakthrough at some future point and when is a cure really a cure?  How long after treatment and clearance have there been breakthroughs anyway?  In any case, don't bother thanking me.  I entered this trial believing it to be the option that held the highest chance of success for me as a 1a naive with the least amount of risk and discomfort.  Perhaps those who could afford to do otherwise entering trials that include ifn are heroic but not me who would do anything at all to avoid it.  I am so embarrassed when any of the nurses thank me especially in view of their paying me to boot!  At any rate, like you I have been one of the lucky ones with a low fibrosis score -- an f=0 or 1.  With that information and good labs over the course of decades, I have decided against rescue if that should be necessary and, at 64, will probably put this baby to bed once and for all regardless of the outcome.  It is bad enough that this virus has taken over my body over the last 40 years;  I don't want it to take over my mind any more than it has already in the last 20 years that I have known about it.  But I do think it is you and willing and a lot of others who have stuck with this journey despite low fibrosis and accumulated and provided lots of useful information for others to make informed decisions who should be thanked and considered heroic.      

[dointime]

PS -

And without wishing to put a damper on anything - we do still have to find out how well the all-oral regimen will work!

We have one proof of concept so far from BMS that SVR is possible without ifn.  That is already a huge step and revolutionizes many a theory about SVR.  What we don't have yet is any idea about the success rate of the all-oral.

So mobilizing the troops may be a little premature.  By this time next year we will have a much better idea of the outlook for the next 5 years.  That will be thanks to all who have done the trials over the years to get us there.

dointime





        

[dointime]

All oral with few sides is of course everybody's dream come true.  You won't find any argument here about getting these drugs on the shelves sooner.  I have just sat through 4 years since my trial to see incivek finally get approval.  The people who have the experience in this area are the campaigners of the aids epidemic.  If someone wanted to pursue your suggestion, looking them up would be worthwhile.    

A certain amount of testing time can't be helped.  It takes time for recruitment, for the trial dosing to complete, and for the followup.  Many trials are now completing in 24 weeks or less, instead of 48 weeks, so that should speed things up a bit.  Also, there is a hope that the approval of the first 2 DAA's has opened the floodgates and the FDA may be geared up now for the next batch.          

I never heard of the drugs getting approval in other countries before the US.  Certainly Europe follows behind the US.  Maddeningly so.

Wishing you all the best and SVR from your trial,
dointime    

[curiouslady1]

The finding that the all orals are proving to have little or no side effects and are quite powerful in the right combination ought to put a big bug up someone's butt re. approval of these drugs.  I have heard more than one person at my research site ask the winds why drugs get approval in other countries before the US.  Anyway, I think "fast tracking" is not really enough.  I am hearing 5 years for PSI 7977.  Surely, someone ought to be able to think of some creative way of using the internet to politicize this issue.  All orals with little sides would not only be a money maker for the Pharmas but a life saver for many.  A shift to all oral represents a radical leap in the area of treatment of virus.  

[dointime]

Thanks for this.  I take your point about the ifn response.  I think my classification is a Responder Breakthrough. :)

I would really rather not do SOC again but if that's what it's gonna take then so be it.  If Pharmasset's PSI-7977 does not live up to it's aspirations of replacing ifn then my eyes are on Gilead who are currently testing some good looking quad combos.  Unlike previous boring AASLD's, the one a year from now should be sensational.  I watch this space.....  You won't need to.  You'll be done soon, for good I think.

May you live long and prosper,
dointime
    

[willing]

dointime : sounds like a good plan and as long as FS monitoring continues to show no progression there's time to wait. It's always hard to foresee the future but it seems likely that approval of a single non-NS3/4A DAA (eg BMS790052, R7128, VX-222) to be used with ifn will happen before an all-oral no ifn regime. Susan400 just received conclusive evidence of ifn non-response so avoiding ifn dependence in a future tx seems clear. However in your case the extent of your ifn response still seems unmeasured, and an IL28B won't really settle it. A quad tx with say BMS790052, Boce and SOC may get you to SVR years before no-ifn approval.

Ev: all the best - adding ntz if you're not seeing about a 0.5 drop by w2 may be something else to consider.

Susan400: making trials available to those who actually need the meds - what a concept! I hope it flies.

[dointime]

streamline569 - Hi -  I haven't done the IL28B test so don't know.  I agree results would be interesting.  As I would have to pay for it myself I have been putting off doing it in the hope that my next tx will be ifn-free and therefore make the result irrelevant.  If I have do go another round with ifn then I might still do it and will post my results.

crossroadsec - I hear you and I had to laugh.  I'm no different than you in that I'd rather be run over by a bus than look at another round of ifn and riba.  From where I'm sitting, helping others is a nice side effect of the trials, but getting SVR is a whole lot better!  Best wishes with the triple and hope that this is the last round for you,

dointime        

[crossroadsec]

This sounds like some hope is out there. I just started my triple therapy, but it's good to know that the medical community is determined to deal w/ all the varients hep c patients encounter.
I thot last night that if this didn't work, I don't know if I could do it again. So I hear that loud and clear. But life is precious and def worth fighting for. It freakn makes me smile to read all ur posts about going another round.
I was reading my huge honking statements they make me sign w/ all the meds about potential se n no guarantees. You know what? If they learn from our failures, we've only helped future patients have a better go of it. Still *****.. Karen :)

[streamline569]

Hi DT. I was wondering if you know your IL28B type. Sorry I always find it interesting. I know they didn't have the test years ago but find it interested to see if it can give us insight now on how different people reacted to treatments.

[dointime]

willbb - I was self employed so no group insurance for me, but great for you if you can get it.

evangelin - many thanks for the vote of confidence.  Wow, that's a big step for you and Joe to go for the Victrelis!.  I so wish for it to work for you and will be watching for your posts.  That Tom Hanks movie - I mentioned to my doc about all the people waiting in the warehouse, which got me his strong disapproval of the term and a stern lecture that it was distasteful to use this term when referring to human beings.  Well we all know this and use it tongue in cheek, but I was reassured that his humanity was still intact despite all the people that have died on him of aids.  

nygirl - hi there, I hate, hate, hate, this b***** f****** virus too!      

Hector SF - great you chipped in.  I always like your posts which I find informed,  accurate, and well balanced - a rare combination.  Have been following your situation closely although not directly posting to you as I felt I had nothing material to add.  Just - wishing you the best possible outcome.
I am a geno 1b.  Your advice is good.  I'm going to wait a year and not sweat it about the price of the meds then review the situation.  

susan400 - it is your so interesting posts that encouraged me in the first place to think that it might be worthwhile posting this thread about my own experience.  What you say about this trial for the protease failure patients is very interesting.  I asked my doc about this and he said that there were so few candidates that recruiting would be too difficult.  Well the UK is a small island where they are scrimping on doling out the drugs so no surprise, but different story in the US perhaps.  Hey won't it be funny if your doc is the only one who runs this kind of trial and we all turn up for it.  In a year or two he might need to rent a football stadium.  On that basis Susan, this could happen much quicker than you expect - but hard to predict.

dointime              

[susan400]

Yesterday, at my follow-up appt., my doctor was saying that him and some other researchers are trying to work on a trial for Telaprevir failure patients, probably something all oral, alone the line of the Pharamasset combo TX.  He said that he had several Telaprevir and/or Boceprevir failure patients (which surprised me actually). He told me of one case he had (no name given on the PT, obviously), where that pt had done numerous TX's, including Infergen and had never been able to clear.  Then, that pt got into a Telaprevir trial, cleared, stayed clear for 48 wks (actually had the Telap.for part of that 48 wks) and then, on the month follow-up, was again detected.  This patient is still detected on subsequent blood work.  So, my doctor is saying that him and his colleagues are investigating putting together a trial specifically for the Protease failure patients, using something like Polymerase Inh + other agents, w/o interferon.  I looked right at him and said, "How long is this going to take?.., because I am tired of doing TX's and I am not going to be doing this when I am 60 yrs. old?"  He looked right at me and assured me that this trial would be in place for protease failure pt., possibly as soon as 1 yr, but probably not longer than 2.    Now, I want to believe him, but sometimes, I do know that these things can drag out.  Also, I asked him, how do I know that I won't get the wrong arm again?  He said that this trial would not have a placebo arm because it would be for pts who had already had TX failure.    I know my insurance is lousy and I certainly don't want to wait around for these new drugs to be FDA approved.  I guess I'll have to just wait and see.  Susan400

[HectorSF]

You doctor is correct. As you stated viral breakthrough is related to resistances mutants that the interferon and ribavirin were unable to suppress. So using a antiviral that stops the replications of mutants is what you need. Luckily you can wait.

This is more common in genotype 1a patients. Not sure is you are 1a.

No sense worrying about the price of meds now as it will be years before they are available. Live you life in the meantime.

Hand in there there. Time is on your side.
Hector

[nygirl7]

Evangeline you both are going to go for it?!!!!!!!!! That is very exciting news and you know everyone here will be so rooting for you both.

DT - I'm so sorry I dont know anything about UK healthcare but you've put up such a fight I know something has to come along for you somehow. I hate HCV. HATE it.

[evangelin]

I just want to say that I certainly enjoy your posts.  I hope your wait will not be a long one.  
We are going to give Victrelis a shot but past interferon response is not on Joe's side.  I am adding the Sam-E/TMG/B complex regimine that CS, Willing and some others have used.  We shall see.  We may be back in the queue with you. Kind of reminds me of that Tom Hanks movie where he is stuck in  a terminal. I hope we can all get out very soon.
Ev

[willbb]

Very similar.....a failed trial experiment(altho mine was the NS5A)   Canadian socialized medicine...   and currently mild damage(fortunately)

We do have private group insur. thru employer.(however it is an unknown how much they will cover at this point)..is that an option there.??...

Best to you
Will