Continuation of Alinia Thread Below - HCA and Jim

I started this new one because the other Alinia thread is so far down the page already.  I was interested in your comments.  For convenience, I'm 52, female, 135 pounds, geno 1b, infected in '76, found out by biopsy in '93, VL under 2,000/ml.  No active disease/inflammation.

'98 biopsy showed "mild to moderate fibrosis with very slight bridging and minimal inflammation", VL 1,891,892.  '00 "elevated AFP with concern for primary hepatic tumor".  1/01 started Peg-Intron Trial at 100 mcg per week and Ribavirin 1000 mg daily, dropped back to 600 mg Riba at week 2, by week 4 back up to 1000 mg Riba, week 30 of Peg/Riba VL 150,000, dropped as non-responder.

7/05 biopsy showed "no cirrhosis but early stage 3, scar tissue starting to criss-cross (bridging) through the liver - similar to biopsy of 1998 (perhaps a little worse but not much)"  Doc says "Need to consider retreatment".  Pathologist classified biopsy results as "mildly active (Grade 2) with focal bridging fibrosis (Stage 3)".  VL 3,540,000 IU/mL 12/20/05.  "Please note:  This test measures HCV RNA in International Units (IU) per mL using real-time Polymerase Chain Reaction (PCR) technology.  It quantitates HCV RNA from 10-100,000,000 IU/mL."  Started Riba 200 mg 4 weeks before 1/9, building 200 mg per week till first shot of Infergen 15 mcg daily 1/9/06.  At first shot of Infergen was at 1000 mg Riba per day.  2/9/06 VL 794,000 IU/mL.  Treatment stopped at week 9 due to retinal bleeding.  VL 3/23/06 was 4,020,000 IU/mL.  5/9/06 AST 52, ALT 75.

Well, what do you think?  Thanks.

[ChrisDDD]

P.S.  I don't have the labs from the monotherapy, but I remember it starting shortly after the '98 biopsy, three shots per week, no Riba.  I remember the nurse saying I had cleared at week 4, but it bounced right back and I was kicked out of the clinical trial (despite my stomping and temper tantrums!) at week 24 as a non-responder.  I don't remember what my ending VL was, but it certainly wasn't zero!

[HCA]

Jim,
I'm reading that there was INF monotherapy in '98.
This would be pre-peg,so three injections a week.
The nurses observation that this showes 'clearance' at week 4 ,but then 'bounced back' would have been based upon a ,by todays standaeds,extremely crude quantification test,possibly with a sensitivity not even acurate to say 650 copies per ml (or worse) which would have been the standard at that time.
This plus the fact that the information about 'clearance' is anecdotal means we can diregard it as relable data.
I trust that the raised Alpha Fero Protein warning situation has been carefully monitored since and that there are ultra sound scans ongoing.
This is a difficult case-the history of non-response and retinal bleeding make it difficult to suggest a treatment plan.
Alinia monotherapy (and I'm no expert on Alinia) is not going to get us where we want to be.
The retinal bleeding apparently occurred at week 9 of Infergen which is the most aggressive of the IFN treatments.
The patient history most particularly the retinal bleeding will, it must be faced,not ehhance Chris' chances of getting Vertex whilst in clinical trials.But yes keep pushing.
One scenario is that a short course of Peg plus Vertex 950 will do the trick (viral clearance wise) after FDA approval.
I agree entirely that we need to know where we are today in terms of liver damage.
I don't know if there has been an endoscopy,but one well may be indicated as monitoring for varices seems sensible at this stage of the game.
Chris needs to be under a first class hepatologist, and I hope this is the case.If it is not then one has to be found,and a consultation arranged.
Once again,I am not a doctor and have simply attempted to give a common sense response to a complex case history.
Look forwar to hearing of further positive developmants.

[jmjm530]

I just found the previous thread and now remember our conversation regarding the Vertex trials where you were told the retinal bleeding might exclude you.

As I mentioned earlier, I wouldn't back away from the trials based on what one person told you on the phone. Better to speak and get examined by a doctor at one of the trial centers as there may be some flexibility, as often is the case.

In any event, I still think it's putting the cart a little before the horse. In other words, consider getting a more current biopsy to first see where you stand. Meanwhile, do some research and speak to some doctors (opthamologists/hepatologists) more about your retinal issues and -- trial aside -- ascess what the actual risks to your eyesight are if you treat with current SOC, or current SOC plus Vertex, etc.

-- Jim

[jmjm530]

First, I'm a little confused about what happened in '98. You first described treatment as Peg and ribavirin, and later as "monotherapy". Monotherapy would be just one drug -- for example peg without ribavirin.

Also, you say you were dropped as a non-responder but also say you were non-detectible at week 4? If that is correct, and the virus "bounced right back" that would make you a *responder* with a viral breakthrough. Entirely different.

Working under the assumption you were non-detectible, and then the virus broke through, perhaps the reduction in ribavirin was the problem. However, a lot of assumptions here.

But, then on second go-around, you pre-dosed with ribavirin but according to your numbers you were a slow responder as opposed to a responder. (Frankly, I question why they just didn't re-treat you with the same drug and try and maintain the ribavirin with a helper drug (Procrit))... but anyway you didn't respond the second time in spite of what appears to be a full riba dose. I'm going over it like this just to make sure that I'm getting the facts straight from you.

My advice is first to clarify all of the above factors by getting hold of your complete medical records from both the trial doctor  and your second treatment doctor and then bring them to a third hepatologist (liver specialist) to re-evaluate the entire thing, including the issue of retinal bleeding which I don't feel qualified to comment on.

Also, if it were me, I'd ask for another biopsy as it's been three years since your last. What your doctor described as an "early stage 3" might be described by another patholothist as only stage 2 since the bridging apparently wasn't fully mature.  (I had similar issues with a couple of pathlogists reading my slides).

A more current biopsy will help connect some dots and determine if indeed if your liver damage is getting worse, or if indeed in a holding pattern. An alternative, is to get a Fibroscan at either one of the 3 or 4 trial sites in the U.S. or with one of our members here, "hepatitisresearcher" who has already offered Fibroscans to at least two of our members who met his requirements. If it were me, I might do both in your position -- needle biopsy and fibroscan.

After you go over the whole situation with your doctor, including hopefully another biopsy, you can revisit which way to proceed -- either to treat again, or go into a watch and wait mode.

As to Alinia, the information is still sketchy as I see it -- and my understanding is that it would have to be used with peg anyway. So, I'd keep one eye on Alinia, but I'd keep a bigger eye on the current Vertex trials. Preliminary SVR data from the 24-week group should be available very soon with more data flowing in all throughout the year.

All the best,

-- Jim

[HCA]

Just re-read earlier thread.
Doesn't change anything, but I do note that you have seen a 'best in world ' doctor-good!
His enthusiasm for you as a Vertex candidate is encouraging.
I have pressed my own doctor to get me on one of his Vertex studies,but the protocols far outweigh any compassionate considerations.
Apologies for the typos in my earlier post.

[jmjm530]

On re-reading I see the '00 mono tx so that makes three tries. I also see that in your previous thread your doctor is trying to get you an exemption for the Vertex trial.  I'd still ask for a new biopsy to know where you stand in terms of liver damage so you can best weigh your options, including watching and waiting. Also, assuming you do re-treat -- trial or not -- I'd want more information on how serious the retinal bleeding issue is. Is it just a matter of if you start to bleed again that you stop the meds and you'll be OK. Or can you develop permanent damage, etc.

Wish I could be more helpful but we're not doctors here and even if we were, I don't see any crystal clear answers as so often is the case with HCV tx decsions.

All the best,

-- Jim

[jmjm530]

Thanks for the detailed explanation.

My understanding is that the decision for inclusion/exclusion is made by the doctors running the trials themselves based on Vertex guidelines. Maybe the doctor needs to run it by Vertex to get their input, although based on what you say, it seems he might be able to make the decision himself based on input from the eye doctors you saw. I would just keep pressing your medical team so they don't drop the ball if you really want to get in. Probably wouldn't hurt to mention to your doctor that Vertex said it's basically his call. Sometimes you have to lead these MDs a bit, world class or not.

That said, I still think you should ask for another biopsy. Just don't see the urgency to treat if your liver damage hasn't progressed, especially in light of your past problems.  Even your doctor said in his report to "consider treatment", which to me means he left open the door for watch and wait. At least have the discussion with him. If indeed Vertex pans out -- and we might find out pretty soon (preliminary svr data within days or weeks from the 24-week group) -- you can always jump in at a later date.

So, if it were me, I'd both push to be included in the trial and push for the biopsy at the same time. Then make a decision after the biopsy.

All the best,

-- Jim

[ChrisDDD]

P.S.  Vertex didn't comment on my question about retinal bleeding being an automatic exclusion from PROVE 3, so I hope that means they don't see it as an issue and will defer to the treating doctor at the hospital, my best-in-the-world doc.

It also bears mentioning that, consistent with the article from HCV Advocate re retinal bleeding, that during Infergen/Riba I developed high blood pressure.  That is now under control with medication.

So if you put my three issues together with the article from HCV Advocate, I'm 52 (over age 45), had high blood pressure (which I no longer have), and was on interferon, I would be in with the 47% of patients who develop this problem on treatment.  Off treatment, it resolves.  It most definitely CAN lead to permanent loss of vision; therefore my reason for and willingness to undergo much more frequent ophthalmic examinations of my retina, now that we know this is an issue.  I had never had any retinal issues before the Infergen/Riba debacle, and also have pages and pages of notes from my local liver doc while I was on Peg/Riba that say "Eyes normal.  Fundi sharp and clear," etc.  No problem AT ALL with eyes on Peg.

[ChrisDDD]

Thank you both for your help and input.  Everything HCA said is correct about my treatment history.  I actually had forgotten that I had ever cleared, but I remembered just the other night being so excited when the study nurse for the '98 monotherapy (pre-Peg) said at week 4 I had cleared to zero, and then she cautioned me not to get too excited because it could bounce back.  It did, and I was kicked out of the clinical trial at 24 weeks as a non-responder.

Each treatment I have had, mono in '98, Peg/Riba in '00, and Infergen/Riba in '06, I had a significant reduction in VL that to me equates to PARTIAL responder, but the doctors insist it's NON-RESPONDER.  My local liver doc is pretty adamant about not even putting me on maintenance interferon after the retinal bleeding, but the retinal doc said though mine was the worst he'd ever seen, he would examine me as often as any liver docs recommended.  He really wants to help me.

I took my retinal photos to the retinal specialist at this large teaching hospital that will be running a VX-950 trial (is already running PROVE 1), and he didn't think the damage was as bad as the local doc did.  He said that now that we knew it was an issue, more frequent retinal exams would probably be well-advised in my case instead of the every 3 months recommended for most patients.  This second-opinion retinal doc works closely with my best-in-the-world liver doc, whom I saw two months later.  The best-in-the-world liver doc has all my records, which I sent certified mail tabbed and indexed for lab work, biopsies, VL, etc.  I also took my own file with me for our appointment June '06.  He agreed with my having stopped treatment NOT because of the retinal bleeding but because it wasn't working, and that no available treatment would likely ever work for me, which is why he was so enthusiastic about my getting into PROVE 3.

Now, here's my question.  We left it that this best-in-the-world doc would advocate vigorously for me to get into PROVE 3 and ask for a protocol deviation due to the retinal bleeding, but that Vertex would have the final say-so and that he could not override Vertex's decision.  I e-mailed Vertex about this, and here is a portion of their response:  "Vertex is not involved in the selection of subjects for clinical studies; this is up to the investigators at the clinical sites."  So is my best-in-the-world doc the investigator or will Vertex have its own investigator at the hospital?  I want to know WHO makes the decision!  Both keep telling me that the other makes the decision.  Am I misreading something here?  If my doc makes the decision, I'm in!?  The study nurse at the hospital insisted Vertex makes the decision.

Sorry this is kind of long, but I find the following very pertinent, and e-mailed it to both this study nurse at the hospital and my best-in-the-world doc:  

"See:http://www.hcvadvocate.org/news/newsRev/2006/HJR-3.4.html

"As reported in the January 2006 Journal of Hepatology, Louis D

[HCA]

I have read the latest posts.
The most important information is that there are no clinical complications of liver disease known to be developing.
'Partial Responder' is an antiquated phrase which has been rightly dumped.
We now know that there is no such animal,and that Chris is indeed a proven non-responder.
The ramifications of the Prove trials are enormous-millions of lives,billions of dollars.The entire pharma market and the stock market is watching Vertex like a hawk-possibly one of the most imoortant drugs of our time.
Everyone wants smooth progress through to FDA approval.
Can the big Doc swing it for you,and would it be wise for him to do so?
I am sure wants to help you but there are thousands upon thousands of patients clamouring at the gates!
The better the trial results the better for everyone.
Why when they have the pick would they choose a bruised apple like you (or me)?
Would you select a patient with a history of interferon induced retinal bleeding regardless of the comforting articles?
It's not so much the worry of permanent opthalmic damage but the fact that if they have to pull you out it will have to be included in the data presented to the FDA.
I hope you get on,but I'm not sure that anyone is going to stick their neck out for you.
I may well be wrong-I have been wrong before-but I think the most likely scenario is that you hang in until the drug comes to market.
I think you have time for that.
Keep pushing to get on the trial,you may be included but don't despair if your'e not!!!!!!!!!

[ChrisDDD]

First, thank you both for your help.  You make such excellent points.  My question still remains that I DID ask my "big Doc" (easier than best-in-the-world doc) who makes the decision, and he continues to say it's Vertex.

HCA, I couldn't agree with you more as to who Vertex would pick; i.e., if I were Vertex, I wouldn't pick me.  The good thing that could come out their picking me, however, would be to demonstrate that those 47% of patients who have had retinal bleeding on interferon do not have that problem on VX-950, opening the door to people like me.  Of course, as we all know, that's a big IF.

I've read other posts here expressing the same enthusiasm I (we?) have about VX-950 receiving FDA approval.  I certainly would not want to be an impediment to that fabulous goal in, like Jim said, having to be pulled from the trial for X reason.  That could set Vertex back, and that could hurt many, many people or even cost them their lives.  I don't wish that on anybody.

I'll let you know how it goes, but I don't know if I'm going to be in any hurry to get into HCV-796.  I want the VX-950.  And, yes, I agree with both of you that everyone is watching this drug as hopefully the new cure for this rotten disease.  I'm also now watching Vertex as a stockholder!

[Forseegood]

Hi, hope the SVR is suiting you well, as I'm sure it is...read in some thread the vertex data is coming in a few months? do you have a beat on this or a timeline, however rough? I just had some other stuff done (no, not a facelift, ha ha!) and I've been taking a little VAKA from all things hep c, (you know how that is) anyway, just wondering since I haven't been following too close lately...hope youre well and enjoying your Japanese beer with a few sushi now and then...

[jmjm530]

Some if not all of the 24-week arm have already or will soon finish treating. That means preliminary SVR data will soon be at hand. The post-tx four-week data should be major news and the post tx 12-week data even bigger news. I've asked several Vertexers when the viral load test results will be released but haven't heard back. Yes, still enjoying Sushi and that Japanese Brew -- shame on you Forsee for starting up another alkie thread :) -- but as of this afternoon, I hopefully will be switching to a Spanish brew or at least a spanish brewty :)Hope all is well. Too lazy to google "VAKA" -- so what kind of trouble you getting yourself into now?

-- Jim