New Drugs. New Treatment Decisions.

[jmjm530]

Recently, someone at another discussion group asked me how I thought the newer protease inhibitors like Vertex should affect our current treatment decisions. Here’s an edited version of my answer.
-----------------------------

That's an excellent topic for discussion!

"To treat or not to treat" has always been a controversial issue.

Nowhere is it more controversial than genotype 1's with no or minimal liver damage, i.e. stage 0 or 1.

In this group, doctors are split. Some advocate treatment, the idea being you have a better chance for SVR if you hit the virus early in the cycle, when you're younger, healthier, and when the liver has little or no scarring.

Others advocate a "watchful waiting" approach with regular lipid monitoring and follow-up biopsy in 3-5 years. The idea here being why expose yourself to the side effects of these powerful drugs when your liver is still in decent shape.

In this debate, I tend to favor watchful waiting, although I respect anyone who decides to treat as long as they're making an informed decsion, weighing the pro's and con's. The only right answer is the one that's right for you.

That said, the new protease inhibitors in trials -- like Vertex --  seem to be shifting the "treat or not to treat" paradigm in this select population toward "not to treat".  Because even if we're off with the project 3-5 year release date,  this group still has time to wait.

PART II WILL SHORTLY FOLLOW...

[jmjm530]

PART ii

Less clear is the treatment approach with genotype 2's and geno 1's with signficant liver damage, i.e. stage 3 or 4.

Geno 2's with the current drugs, now have an overall 80 per cent chance of being non-detectible with only 24-weeks of treatment. And some select groups are showing similar success with only 12 weeks. For these reasons, many geno 2's are advised to treat now, even with no or minimal liver damage. This makes sense.

As to geno 1's at stage 3 or 4, the question is how long can they afford to wait? Because no one can guarantee these new drugs will pan out in time, treating now with current drugs is still a viable and often the best option. Keep in mind there was a similar excitement about BILN 2061 a few years ago that didn't pan out. So nothing is guaranteed.

Beyond "to treat or not to treat" an equally important issue is how will these upcoming drugs affect non-responders, relapsers and the tx decisions they have to make.

Recently, I spoke to a leading heptologist/researcher and asked what he's doing with relapsers these days. To my suprise he said he's not re-treating most of them with current drugs. The reason -- the promise of the upcoming protease inhibitors like Vertex

We all hope the new protease inhibitors will be the big breakthrough. Our entire community certainly deserves this.

But at this point we still have to be cautiously optimistic and carefully weigh how we factor these new drugs into our tx decision, but make no doubt about it, they certainly are a factor to consider.

And because new developments are happening so fast, the decision that makes sense today, may change tomorrow. One way or another.

-- Jim

[couldn't think of a nickname]

you basically summed up my line of thinking on it. Granted, I don't feel great, with chronic myofascial issues/muscle issues, which makes it seem far, far away. However, I have been following the course of this drug since I found out about it 4 years ago-meaning more than half the wait has passed, including the first trials in humans. I am 1B, got it from a blood transfusion 21 years ago, when I was a kid.

[miked]

I'm a 1b with 0-1 scarring.  After 36 weeks of tx I was stopped because of a viral breakthrough.

With all the buzz about VX-950, NM283, SCH-6, etc. I might have waited to tx. Right now I'm watching the news on all the  protease inhibators and would consider a clinical trial.  Does anyone out there have information about which drug to choose?  NM283 is being developed by a smaller company but with the backing of big pharma.  VX-950....I read yesterday that it's company committed to a bunch of leased space to accommodate their research needs.  My doc at IU Med. Center is high on SCH-6 but it's not even in a Phase I trial yet.....how do you choose?

After seven months off of PEG+RBV, I still catch myself in foggy moments and my neck and shoulder ache all the time...like arthritis and it began while on tx.  I've heard DDose comment about the same.

Mike

[jmjm530]

I believe the current trials, at least with Vertex, are only open to treatment naive folks but maybe more current info is at http://www.clinicaltrials.gov/

Depending how you feel physically, you might want to wait a bit considering your minimal liver damage. Also, and I'm not 100 per cent sure on this -- I think for at least the next year or so these drugs will be combined with peg interferon and/or riba. Down the road a bit they will be tested by themselves.

-- Jim

[couldn't think of a nickname]

My first post was written before Part II came on. I did want to address BILN 2061, and I should mention I have talked to Boehringer Ingleheim in the past. They are NOT a publicly traded company, and apparently keep secrets better than some CIA agents. They would not tell me their plans for that drug, or about what they were planning in the future. Of course, there are no SEC filings to read for that either.
For those who might not know, BILN 2061 was a drug that eliminated the virus in vitro very quickly. Cardiac toxicity became the problem, and I believe the problem was in monkeys. Due to that issue, the program was suspended.
What Vertex did was they monitored EKG's and other heart functioning tests during their IB and there were no changes, problems, or abnormalities reported. Even though BILN didn't make it, I do belive it helped the others as to what to look for, etc. Was it Einstein who said that he who never failed, never accomplished anything?

Forbes did an article on this drug last January, before the last trial was completed.

http://www.forbes.com/business/2005/01/24/cz_sg_0124soapbox_inl.html
The thing I found interesting was that since the drug blocks an enzyme that is exclusive to the virus, and not the human body, there shouldn't be a side effect problem-UNLESS it is not broken down by the liver well-which was apparently the problem with BILN's drug. VX-950 has not had that problem.

Schering Plough is working on a small molecule PI as well, but there is very limited data on it, and they are behind VRTX by at least a year, or at least 1 phase. It remains to be seen if they can even match, let alone exceed the data out on 950 yet. Yes, I do own VRTX's stock from 9.18, from 5/04, based on a lot of the above.

[NYgirl]

Thanks jmjm - fascinating reading.

As a 1a/1b Grade 2 Stage 2 I've decided to opt for treatment asap.  

But...I was wondering last night (being a/b and reading perhaps overall tx response is lower) what else was coming down the pike.  Explainning in this thread what else is being cooked up is just what I was wondering.  

[v eggie dip]

I'm a bit confused, maybe you can help...

When they say these new drugs will be available in 3-5 years does that mean they will be available only in trials or as a regular routine of treatment options...and will interferon and riba still be a part of the cocktail in the 3-5 years?

As you know, I still have not decided to treat or not to treat (biopsy will play a big role in decision)...Hearing all the stuff on these drugs coming along with less side effects really interest me, however, keeping my age in mind (54) do I have the luxury of wating it out, and what will the "less side effects" mean?  i.e anemia...

Your input would be appreciated....

Thanks Beth

[omyst]

Something to keep in mind if you are a non-genotype 1

Protease inhibitors are small molecule drugs, VX-950 specifically targets geno 1b protease. Notice that all participants in the VX-950 trials were geno 1.

An earlier protease inhibitor BLN 2061, which also targeted geno 1 has been halted due to serious cardiac concerns, but data indicates that non-genotype 1's did not have as good a response.
VX-950 may not have the same drop off in non-genotype 1's, but that won't be known until tests on non-genotype 1's are conducted.

http://www.hivandhepatitis.com/2004icr/hepdart_2003/docs/011404_a.html

[couldn't think of a nickname]

VX-950 should be on the market as an approved drug in 3 years, if all goes according to plan, and so far, they are at, or ahead of schedule. Interferon will at the very least be additive, at best, synergistic. They are doing studies on it with and without interferon. They still feel there is good potential for this as a monotherapy, and I think Phase IB data does support that, without a doubt.
They just had a webcast of a presentation this morning, where they reiterated their views: IND (Investigational New Drug Application, which is filed with the FDA to support further clinical trials) will be filed soon, Phase IB to start soon (interferon and 950) Phase II to start this year and to be completed next year, with SVR data, Phase III in 2007, and an NDA filing BY (their words) 2008. An NDA is a New Drug Application, which is filed by a company to the FDA when they submit their drug for approval. In normal cases, a decision is made in 12 months or less. In this case, since it is considered an unmet medical need, the review will be a "priority", which means an answer in 6 months or less.

That is how the mid-late 2008 timeline for the drug to be approved is arrived at.

[couldn't think of a nickname]

I think I may have an answer as to the non geno-1 issue. NS3/4 is the enzyme that blocks the virus from the immune system, and I believe that to be the case (I could be wrong) in all genotypes. BILN did NOT target NS3/4, VX-950 does. 950 "uncoats" the virus (which is protected by NS3/4) and allows the immune system to now be able to identify it and kill it. The drug has a half life about equal to the half life of the virus, which is critical.
I have a call into VRTX (who has not been good at returning them) and I will ask them about that.

[cuteus]

all we need is to see what the SVR rates are per genotype and we can compare the effectiveness against current protocols. So far all I see is the clearance rate.

[jmjm530]

Your questions are good ones.

"couldn't think of a nickname" lays out one projected timetable, although I've heard the drugs could come to market sooner if fast-tracked for certain patient populations.

So, yes, the drug currently is in trials and currently being tested with and without inteferon. What they will end up with of course will depend on the trials.

As far as whether you should treat or not treat, this is a very personal question of which I tried to offer some guidelines in my first post. Once you get your biopsy back you'll have more information.

As far as having "less sides" -- yes, that's the word.

-- Jim

[scruffy]

Good topic Jim. Thanks. frank

[MichaelT]

Concerning the continuation of interferon in future treatment soups, I believe that if the goal is virus elimination, interferon + riba + inhibitor <i>x</i> will be the cocktail. We have as a general model treatment for HIV. Before anyone jumps my butt, please note the use of the word <i>general</i>. Uh, I believe it was protease inhibitors that turned the corner for HIV treatment. They were not a cure, but increased life spans and maintained better levels of general health longer. What is probably similar is that various inhibitors aren't likely to be a cure in and of themselves for hepC, but, as a sledgehammer to knock it to the ground and interferon/riba as the bullet to the head, so to speak.

[jmjm530]

Recollection a little foggy, but I do remember reading about the similarities and difcferences between the use of protease inhibitors between HIV and Hep C. If I remember correctly, they differentiated between the two types of viruses and I believe the conclusion was that the protease inhibitors could actually eradicate the virus, not just knock it down as with HIV.

Intially, yes, it will probably be cocktailed with peg and riba, but this is as much an FDA requirement as anything else. The longer term goal is to use it either as mono-therapy or what many guess would be another type of cocktail but without inteferon or ribavirin. Exciting stuff!

-- Jim

[couldn't think of a nickname]

There are critical differences between HIV and HCV that are important as far as "cures". First, HIV is a retrovirus that integrates into the DNA (I belive, I am not an expert here). There are hidden reservoirs of HIV which is why it hasn't been cured-yet (I'll elaborate later). HCV is an RNA virus with no hidden reservoirs and many in here have been "cured", even if that definition means different things to different people. Many scientists will tell you that the cocktail approach to HCV will become a thing of the past. Targeting the NS3/4 enzyme is a breakthrough that many believe (including myself) will transform treatments just like the cocktail approach to HIV did-In other words, the cocktail approach is the best approach for HIV, but will be the least effective FUTURE approach for HCV. Remember, 950 did what combo treatment couldn't do, and faster. In 14 days, 950 alone had a 4.4 log drop, whereas in 28 days, current therapy averages a 2.4 log drop. That is 100 times more potent in half the time. That tells me that the cocktail approach may not be needed. Granted, many may choose interferon to go with it, because that would probably be like killing a gnat with a sledgehammer.

My family doc told me a few years ago that PI's would transform HCV therapy and better things were coming, and he said there could be real cures. He did not know about 950 though until I told him about it.

My note on HIV: Recently, I was viewing the drudgereport, and saw a headline about a possible cure for HIV, so I read it as it intrigued me. In England, there were 4 people with HIV that were given standard treatment, but they added an anti-convulsive drug and another compound to it. 3 of the 4 completed the trial, and those 3 had an average 75% reduction in "hidden" virus. The reason why they did this test, was, that apparently HIV hides in a certain cell that the anti-convulsive drug is active against. That drug brought out the hidden virus so the haart could kill it. Expanded trials are underway, but it was seen as a significant breakthrough.

[couldn't think of a nickname]

Very good discussion you started. I think a lot of good questions are being asked, and a lot of good info is being distributed.

[v eggie dip]

Thanks Jim for your info, this was a valuable thread for me...

After I receive the results of my biopsy I am hoping to come to you and cuteus for your personal opinions...You both seem to have a weath of knowledge on this virus and cuteus you are female and although you're younger than me we seem to have some pre exisisting conditions in common as well as genotype and you made it, you're my inspiration...

Thanks again to you both...Beth

[cuteus]

it is ultimately up to you, even if mild damage, to decide how badly you want hcv out of your life. I firmly believe that if drs intervene promptly against anemia and prevent oxygen deprivation damage, there will be less long term effects, and less people quitting tx. It is not fun ot tx, but what a reward it is after it is all over, and you can say; I WAS hcv positive.


here are some techno stuff about viruses:
http://vir.sgmjournals.org/cgi/content/full/81/7/1631
http://cmr.asm.org/cgi/content/full/11/4/614
for those who have the inclination to understand the ins and outs of hep c and others.

[v eggie dip]

thanks cuteus, I will check it out

[NYgirl]

Hey C

What do you mean treat against oxygen deprevation and anemia?

This sounds like something I need to know (we) for the future if it will help us stay in tx and help with the sx!

:)

[cuteus]

I am not very good at explaining technical stuff, but hemoglobin is how the cells transport the life giving oxygen to all the organs. Less red cells=less hgb= oxygen deprivation, which can't be a good thing, right? Riba destroys red cells at a rapid rate.
check this article on the importance of treating anemia, sponsored by the makers of Procrit of course, but interesting to know;
http://www.mydna.com/resources/news/200407/news_20040715_bbanemia.html

[NYgirl]

Thank you I get it. I am printing this out so that WHEN my doctor thinks I am being egotistical and know more than HE he will have reasons to LISTEN to me.

I do not believe doctors are NOT fallible...and I want to be armed and prepared.  I want to get better...much more than he wants me to get better if you know what I mean.

Thanks for the link.

[jmjm530]

I have a feeling Cuteus' is out binging on Champagne celebrating her SVR so I'll jump in. :)

One of her points has to do with agressively treating anemia on treatment.

To oversimply, anemia is when your hemoglobin drops to ten or below, or when you have more than a two-point drop from your pre-tx level in less than a couple of weeks.

So, let's say your hemoglobin now is 13. If it drops to 11 after two weeks or so on treatment, you may start feeling very fatigued, dizzy when you stand up, even out of breath. It's anemia caused by the ribavirin.

What you want to do is first make sure your doctor does a hemoglobin test at least every other week during the first 12 weeks of treatment. I had mine done weekly. That way you will know what is going on.

If you do develop anemia, the solution is to treat it with weekly injections of a drug called Procrit. It's really a miracle worker and in most cases will get your hemoglobin up to par within 2-4 weeks. Unfortunately, many docs are too slow on the draw and people suffer the symptons of anemia needlessly, or worse -- they have to reduce their ribavirin dose or even go off treatmen.

Vigilant monitoring of your hemoglobin level and early intervention with Procrit is what you want. This is something I recommend to everyone to discuss with their doctors prior to being treated.

-- Jim

[NYgirl]

Ah my doctor DID say I had to have a blood test ONCE A WEEK EVERY WEEK during treatment to watch my red blood cells.

Now I know why.  I had no idea how important this could be.

I am going to "attempt" to work through this (need the insurance) and if I get fatigued and the Procrit will help (have seen the tv commercials for chemo patients) I am on it.

I am so glad I asked.  It's so important to know what we are coming up against.

Is the main reason you get fatigued due to the anemia you think?

Thanks Jim and Cuteus (ps not too much champagne C...you aren't used to it anymore) LOL hahahah!  YAY!

[MichaelT]

Yes, yes, yes, I know there is a difference between HIV and HCV and I did state "general" model as an acknowledgement of the differences. Investigations for HIV treatment have resulted in investigations applicable to HCV treatment.

Currently we do not have much to base a belief that any of the various inhibitors will be a cure. We have hopes. I have no crystal ball, but I envision, if not a continuous combo of inhibitor/interferon/riba, an initial assualt with that combo with follow up treatment with just inf/riba. Anyway you slice it and dice it, a shorter, more effective treatment, with less treatment induced damage is the goal.

[jmjm530]

It doesn't happen to everyone, but just be prepared. Anemia, within the first four weeks or so, is the number one reason people either have to stop treatment or have their ribavirin dosages reduced. Either one can dramatically affect your chance of SVR. And even if they don't stop your treatment, you will not have a lot of fun huffing and puffing around the house.:)

It's good your doctor's office is taking weekly blood counts. The results are usually in within 1-2 days. Ask that they call/mail/fax you the results as soon as they're in. In my case, I have it noted on my requistion form and the blood results are faxed to me directly by the lab.

Fatigue on tx is not only caused by anemia. The interferon can also wear you down.

-- Jim

[miked]

Wow....you're the first one to mention that you're investing in the stock market based on this insider knowledge! LOL.

Obviously I want the biggest return on investment - my life.  

With that said, what's your opinion about all of the protease inhibitor companies' stocks???  I've had it on my to do list for three months to by stock in Vertex, Idenix, Schering or all three.  Any tips?

[couldn't think of a nickname]

LOL but I would be careful-none of this is insider knowledge-everything I know is public knowledge. I found out about it by looking for news on HCV. I actually don't follow the other companies that much, because my orginal path made me believe this might be best in class....and it does look that way. I did not know much about Schering's at all until very recently. Vertex actually mentions it in their presentations. It, too, is a small molecule PI that has been highly active in replicon assays, but there is no other data yet, nor in humans. It will have a high barrier to reach in order to surpass 950. I am not that excited about Idenix's drug, simply for the fact that even though it is better than current therapies, (or with current therapies) it's data is not as impressive. I think that in this area, any company that comes out with good data or approval will see their stock react well.

As an aside, I think the way I found out about VRTX and 950 was that during the bubble days, it was a high flyer, and my news feed might have had a press release about 950. I remember that in replicon assays, it eliminated the virus in 14 days with no rebound. I have followed it, and every press release and web cast since. After the stock crashed from the bubble, it spent 18 months basing. I bought it at the low end of that basing pattern. It has since done very well, with the 950 news and data being the catalyst. My personal rule of thumb is, that when a stock doubles, sell half, manage the other half. I have sold nothing because I feel that this can be a blockbuster. The risk is, if something negative happens, or there are delays, the stock will suffer. It is the chance you take.

With all of that said, Schering's drug could turn out to be better than NM283, but there is no data yet.  Being better than 950 might be tough. They are also significantly behind VRTX, by at least 1 phase, and at least 1 year. First to market is big. Anything that comes after would probably need to be either more efficacious, or safer, or both in order to dominate. If docs get comfortable with something, they may be reluctant to change. The advantage for Schering is, that they are a big name, already known by hepatologists. Phase I is a big step for drugs like these-BILN never made it out of there.

[couldn't think of a nickname]

Mike, I should add that I believe there are 9 compounds in various clinical stages, and 950 has been considered best in class.
One company that neither of us mentioned is Human Genome Sciences (HGSI). I believe that they have a replacement for pegylated interferon in late phase II right now. It is called Albuferon and uses their albumin-fusion technolgy (they are also using that tech. for an anthrax vaccine funded by the gov't). Albuferon has a much longer half life than Peg. Int. and only needs to be taken once every 2-4 weeks. It is possible that if a form of interferon is needed/desired in the future, it could be one or 2 shots of that with a drug like 950. Talk about transforming the treatment paradigm-it would be possible to use a single agent, but if not, 1 or 2 shots instead of 48.
And, you are right, the best return on investment is always the health aspect.
I think many are focusing on possible monotherapies, which is great, but if interferon is needed, HGSI could be a future player.

And no, I don't know all of the other players in this market. I do think the 3 you named are the ones getting/will get much of the future attention. I hope that word of these developments does get out there so that people will be less afraid of a diagnosis and more likely to treat. Only 5% of those infected treat, and maybe 25% know they have it. Those numbers need to change.

[rearfang]

WOW! That was a workout!
Miked--so good to hear from you!
Lauren

[iceboy]

Hello all

I have been away working like a dog. It’s great coming back and seeing the knowledge flowing. I managed to squeeze in the biopsy and have now my full profile. Seems like I fall into the category being discussed here. I would dearly like if you can comment or give me your opinion on if to treat or not. I have more or less decided to treat, though my doctor says I could wait, but she booked me in with a liver specialist in a week to have a final discussion. The specialist just came back from a conference with fresh knowledge. (In short, the docs state there will be other treatment options in 5 years time.) Regardless of my profile, the doc says she would recommend treatment if I was other genotype, and that is also influencing my decision as it must be the same side effects from the TX regardless of genotype (will come back to that later)

so my profile;

1b
378000 VL (Low)
Normal Enzymes
No scaring
Lowest mark on inflammation
41 year old
Probably had the virus 23-25 years

Other health issues;
Joint pains
Brain fog
Skin disorder
Spherocytons (inherited blood disorder)

So, What I have been able to gather so far and is pulling me towards to treat is that I could possibly clear in 24 weeks (just a comfort if TX is killing me) I’m healthy and with this profile, I should have better chances of clearing. If the doc says she would recommend treatment if it was other genotype, are my chances of beating this not optimal at this stage with this profile? As far as I can understand, the only reason doc does not particularly recommend treatment, is because the chances of clearing 1b are so slim, and the treatment is so tough with risk of long term effects!!? treatment would be based on peg and riba

Down sides
Financial, but I’ll cope somehow
Spherocytons. My blood levels are low because of this, but that is natural low. Doc is not concerned about this, and says they have drugs to increase blood levels, if needed! (or adjust the riba dosage) makes me iffy, knowing this is one of the bigger factor for results of treatment!!?? I found out that building up blood levels before treatment does not work. The drugs only build up what has been damaged.
Side effects in general.

Any way, hope you are all hanging in there.
all the best.
iceboy

[iceboy]

Hi Mike

can you tell me how your treatment was. I mean, did you have the 2log drops at the right times, did you reduce riba etc.etc. was there anything suggesting why you viral load went up at this late stage and to what level? sorry, Im just curious.

all the best

[go-girl]

I was just @ "Hepatitis Central" there are some good articles on the left hand side,scroll down to almost the bottom there is an enrollment taking place to do with Shcering Plough Canada for a new drug to take with interferon, interesting articles to check out.

[couldn't think of a nickname]

Ice, it sounds like you are in pretty good shape, considering. I am 1b, have had it for 21 years from a blood transfusion (21 units actually), but the last couple of years my enzymes have been elevated, and I do have a pretty good dose of muscle aches/pains. I had an ultrasound of the whole region 5 years ago and nothing of interest was mentioned to me, so apparently, things were fine. I also had an endoscopy to remove a gallstone stuck in a duct, and again, the GI didn't mention anything of note to me. That is my profile, and I am choosing to wait. It won't be 5 years, more likely 3 for a better option (might be just under 3 now). The sides from current treatment combined with the time, and the 50/50 chance is what has kept me from treating. My PCP tells me he thinks it's ok to wait as long as my platelets are good. He says that is more important than VL or enzymes, and that when liver disease advances, platlets drop slowly over time. My platelets have fluctuated a bit, but last Feb., they were 224,000, which is higher than last year even though my enzymes were up.
Whatever you decide, good luck. This decison is a very individual thing, and there is no right answer.

John

[couldn't think of a nickname]

"This decison is a very individual thing, and there is no right answer."

I shouldn't type when I first wake up. I meant to say there is no WRONG answer. I got up at 7, but I won't be awake until 9.

[jmjm530]

Assuming "no scarring" means stage 0, if it were me I wouldn't treat now. I'd wait for those newer drugs that should be around within 5 years. And even if they're a little late, as long as you monitor your liver on a regular basis with another biopsy in 3-5 years you should be fine.

What I think your doctor is saying is that if you were a genotype 2, then they'd recommend to treat. But you're not a genotype 2, you're a genotype 1. Here's the difference. Geontotype 1's have about a 50% of being cured with 48 weeks of treatment. Geno 2's have about a 80% cured of being cured with 24 weeks of treatment. Very big difference. Much less drug exposure for geno 2's with much better results.

When you doctor says you could clear in 24 weeks, they're referring to the new European directive that allows 24 week treatment for SELECTED geno 1's. In order to qualify you first have to have a pre-tx viral load under 600,000 IU/ml which do. You also have to be non-detectible at week 4 in treatment. Just remember, only 40% people clear the virus at week 4. That means if you went this route, you would have a 60% chance of not clearing.

So, I'll offer you an alternative to not treating now. You could treat and then have a very sensitive PCR test (50 IU/ml or under) at week 4. If you're non-detectible, then treat for another 20 weeks and be done. If you're detectible at week 4, stop treatment and wait to treat another days with the newer drugs. The concept behind this approach is to expose yourself as little as possible to the toxicity and side effects of interferon and ribavirn while still offering yourself a a very good chance at cure.

All said, this is what I'd do, but I'm not you, don't have an intimate knowledge of your complete medical history or personal issues. You could very legitimatley decide to treat for 48 weeks now.

Whatever you decide, don't feel rushed or pressured, you have time to make the decision. See what your liver specialist says, I'm sure they'll talk about the newer drugs. And run the 24 week approach by them if it appeals to you. Let us know how things pan out.

-- Jim

[miked]

"Couldn't think of a nickname" - Thanks for all of the info.  Is VRTX still a good buy in your estimation?  It's at $18 something right now; up 15%.

"Lauren" - Good to see your doing well too.  I've been feeling great and have been lurking periodically.

"Iceboy" - I started tx last year as a 1b; 3 million copies; age 46; caucasian; male; minimal scarring and in great health.  My VL dropped from 3 million to 15,000 at week 12; then to 9,000 at 18 weeks; then 5,000 at 24 weeks.  Then my VL climbed while on tx to 12,000 and they stopped me at 36 weeks.  There was no reduction in PEG-Intron or Riba throughout tx.  Right now I'm seeing Dr. Paul Kwo @ IU Med. Center who categorizes me as a "partial responder".  If I was to treat again using the conventional drugs, I would only do so by increasing the amount of PEG (off-label) and/or increasing the frequency of PEG injections to something like every 4-5 days versus weekly.  Dr. Cecil Bennett in Louisville uses this off-label approach with 1b's because the increase in volume and/or frequency of PEG better decays the virus.  With that said, how does one stand up to a shot of increased PEG every four days???  At week 36 of conventional tx I wasn't about to give up but it really took a toll on my body....weight went from 205 to 170 and generally felt like shxx most of the time.  You have age and low VL in your favor.  If I were you I'd tx but talk to your doc in advance about treating past 48 weeks (72 for 1b's) and also will he give Procrit if blood platelets go down.  Good luck and let us know what your decision is.

[couldn't think of a nickname]

That is a tough question mike, I could argue both sides of the fence on whether it is still a good buy, at least in the short term. On the one hand, they are losing money, and have doubled in price since April on a drug that is 3 years away, and it has a market cap of about 1.7 bil.
On the other hand, they have 9 drugs in the pipeline, 2 HIV drugs approved, a third that has been fast-tracked (they collaberate with GSK so they get royalites on those), MRK is funding 3 different phase IB studies on a promising cancer compound, they have an RA drug that looks good, and a number of these will have data  out over the next 3-9 months, including the other HCV drug MMPD. And, it could be argued that 950 could bring in more revenue than their current market cap, but not for a few years.
Each time I felt it would pullback, it wouldn't drop that far, and then go up again. This is a stock that could be a mover on news, which cannot be timed.
For me, I am holding what I have, but haven't decided to move some stuff around to buy more. If I didn't own any, it might be a different story.
I do think that further positive 950 data will help the stock.
If you did buy it, only buy what you are comfortable with, and keep a floor as to how much you are willing to take as far as a decline.
On the chart side, the breakout in May was real, and strong. The long term trend is now up for the first time in about 5 years.
I would feel badly if I said that it is good to own and then you lost money on it, so I wouldn't do that-but good luck with whatever you decide.
I'll go back to your bottom line-the return would be gravy, but the bottom line is even more important to all of us.

[jmjm530]

Miked,

Sorry you didn't clear the first time. I agree with some of your thoughts regarding extended treatments for "partial" responders but I don't find the relevancy in Ice's case.

Ice has no liver damage, can legitimately decide not to treat, so I don't think exposure to these toxid drugs and side effects for even longer than the normal course makes sense. To me, it's a matter or risk/reward.

If you have severe liver damage, then it makes sense to risk the effects of the drugs in order to get cured. If you have no or little liver damage, then it makes a lot less sense. The approach I suggested for Ice was either to wait. or to expose himself as little as possible(4 or 24 weeks) to those drugs.

If getting rid of the virus at all costs is the issue, I would agree with your advice, but I think we all have to factor in the costs to make the right decision.

I wish you well in your future treatment decisions.

-- Jim

[MichaelT]

Jah. The Albuferon is <i>still</i> interferon, but maintaining theraputic levels once speculated to be about a month.

[cuteus]

and others with extra hepatic symptoms, you might want to add to your list of tests the cryoglobulin assay. If they are present, it can lead to vascular and kidney problems. Remember, HCV is not a liver disease only. If the test is negative and you can manage the aches with OTC, wait a year or so, to see where these trials are going. As you age, your svr chances decrease along with it. The effects of the tx are temporary in the majority of cases, as long as the anemia is controlled. Those temporary sides should not keep anyone from treating, unless they are ready to live in peace with the virus.

[iceboy]

What would I do without you guys. Thank you so much for responding. Jim, you put into words what I was trying to formulate with the shorter treatment plan. Sounds like a "very" intresting option you are talking about....... by the way, the doctor has not mentioned the European directive that allows 24 week treatment. I feel like I have to prepare my presentation of this plan.(and yes, you are assuming right, stage 0)

Like we know, this is a funky virus that behaves somehow differently in each individual, and so little is really known about it. Cutus, I totally forgot to ask for tests for the cryoglobulin. Im pretty convinced I have some sort of that going, and I have read that goes away with tx? (I have one old test with gamma-globulin over limit. does that have anything to do with cryo? Mike, it very scary thinking about this longer treatment. How is it, Im very thin, only 68 kg (I think 150 pounds?) I don´t find anything about if that is disadvantage for tx?

fondly, ice

[fishdoc]

Greetings from the deep south.  I am a 48 year old female, and I found out in 93 or 94 about my Hep C. I have had two biopsies, and don't plan on having another. I have only had a couple of elevated enzymes results, by only a few points.  I have had this most likely 28 to 30 years.  I have decided I am going to try the treatment, I have "waited and watched" and it seems to me a 50/50 shot is finally worth the effort.  Plus, even though I have normal enzymes, minimal biopsy results, 600,000 viral load (the only time I had that done), type 1a, I have intermittent bouts of illness that I am fairly certain are related to the virus.  One question I have is related to insurance.  I have the opportunity in October of switching to another carrier, the current one I would have had to spring for a $2500 deductible, but the blue cross blue shield i am looking at has a "$35 dollar copay for mail in non generic prescriptions", with care mark as their pharmacy.  I am troubled by the fact that pegasys/copegasys is on the list of "requires approval".  I don't want to switch and then suddenly be told no.  Does anyone have any experience with that?  Second question, in looking at research, it seems like the best clinical results are the pegasys/copegasys brand.  Is this still true?

[shads]

I am genotype 1 with a low viral load and stage 0-stage 1. What frustrates me most in deciding whether or not to treat is that neither the liver function tests nor the viral load tests are clear indicators of the state of your liver. You can have a
high AST/ALT and a low viral load. You can have a high viral load and normal liver function tests. You can have a low viral load and a scarred liver. You can have a high viral load and little or no liver damage. Additionally, some of us can only guess at when we were infected and so how quickly or slowly the disease is progressing.
I had a biopsy 8 months ago. If I were sure that my liver is still at 0-1, I might wait for more clarity on protease or NM283 or other treatments in clinical trials. I wish there were non-invasive procedures( the biopsy is expensive and can add to scarring) that could tell you every few months about the state of your liver. I saw at http://janis7.hepc.com/labs3.htm#blood%20tests that new tests are being developed but are still fairly experimental. If only we could have a monthly look at the liver and monitor closely the progression of the diseaes it would be easier to make a decision.
Does anyone know about new tests ot have more info about the tests mentioned on the janis site or any other thought or comments?

[cuteus]

these bottom threads are forgotten after a while, try the upper ones. Hep c is a very frustrating disease indeed!

[kconn14]

I'm wondering if any of you have any input on TMC435? It's being developed by Tibotec and from the results of studies, do far, looks pretty good. But I've read this thread and am impressed with the amount of knowledge shown here. I'm geno 1 stage 3/4 and only found out about it 4 months ago. So, I'm told, I have to make a decision pretty quickly. Someone on another thread mentioned this drug and in investigating I find there's a new trial about to begin where I live.
Should I or shouldn't I? That is the question since I don't like the odds much from standard tx but have pretty much been told I don't have much choice. Oh, and I'm 64 but in good general health. My VL is 3.5 mil and ALT/AST are slightly elevated but the rest of my stats are within normal ranges.
Any info would be greatly appreciated.
Thanks,

Karen

[HCA]

Karen,
You have dropped in on a four year old discussion and none of the participants are around this forum any more.
Things have changed since then and the first of the protease inhibitor drugs telaprevir should be availible in 2011.
With regard to the trial for TMC435 you can learn more by applying.They may accept you or they may not-they are very picky.
In any event prospects for geno 1 patients are better than ever,so you have every chance of a succesful outcome.

[nygirl7]

Kconn just so you realize this thread is almost five years old now and Jmjm hasn't bee posting in quite a while over here.  Ditto most of the rest of the names on the thread sadly - they treated and were cured and are long gone...sad for us great for them!

I just didn't want you to think that Jm is ignoring you. We wish he (and the others my old friends) were still here! I have SVR but am still here but usually people move on in time......I'm just slow!

[WriteItDown]

Hi Karen,

You might want to have a look at the thread I started when my husband was deciding whether to not to participate in the trial.  It's a tough thing to decide, I know!

http://www.medhelp.org/posts/Hepatitis-C/Your-opinions-on-new-Hep-C-trial-of-TMC435/show/1001531

[HectorSF]

For those wanting the details of the new treatments and known results I would suggest viewing video link below by my hepatologist, Norah Terrault at U.C.S.F. Dated 3/12/2009.

It looks like Telaprevir will come to market 1st, in 2011 followed by Boceprevir then many others.

The bottom line is that SVR rates are increased dramatically. There will be many new challenges also. Adverse effects, treatment duration, resistance, etc. etc. But adding a third drug will be a new huge step especially for us Genome type 1s.

Dr. Norah Terrault of UCSF presents an update on treatment of Hepatitis C including use of triple therapy and other novel anti-viral agents. At UCTV.
http://www.uctv.tv/search-details.aspx?showID=15736

Enjoy!
Hector

[WriteItDown]

That was interesting, thanks for posting it.

[Debbie556]

The release for the VX-950 will be out sooner that you think, the clinicals will be completely done and results sent in just after the first of the yr. I know it works and is worth the wait. and it a 24 wk treatment...