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Treatment for Hep C will disqualify you from clinical trials for new Hep C drugs
Why get treated for Hep C using ribavirin and interferon when it will disqualify you from clinical trials for new Hep C drugs? Some trials will accept non-responders to PEGYLATED interferon but will NOT non-responders to nonpegylated interferon. Would it be advisable, if one is a non-responder to non-pegylated interferon, to undergo treatment with the pegylated variety just so one can fail that treatment and become eligible for clinical trials that require non-response to pegylated interferon? There are a few clinical trial that accept non-responders to pegylated, but here are NO clinical trilas that are open to non-responders to non-pegylated. Please note that SVR for Genotype 1 using ribavirin and peg-interferon are extremely low (less than 40%). The only effective drugs are in clinical trials, and likely will not be accessible to you for 10 years. Telaprivir is going on 10 years since it was first discovered, and it is still not available to the public.
Vertex Edges Merck In First Round of Hepatitis C Fight
By ROBERT LANGRETH
New details of studies of rival hepatitis C drugs from Merck and Vertex Pharmaceuticals were released today in advance of a crucial upcoming meeting of liver specialists at the end of the month in Boston. The drugs, so-called hepatitis C protease inhibitors, represent the first class of agents that directly target the hepatitis C virus. Both have substantially boosted the cure rate in big trials, raising excitement among hepatitis c specialists.
While the drugs haven’t been compared directly, it appears that Vertex’s telaprevir drug is is a nudge better. Unless differences in tolerability and side effects emerge, if both drugs are approved, doctors may look at the data and go with the Vertex drug first because its cure rates appear to be a few percentage points higher.
Here’s what Howard Liang of Leerink Swann wrote in a note today:
“Apples-to-apples” comparison of boceprevir vs. telaprevir in treatment-experienced patients is possible for the first time and appears to favor telaprevir. In prior relapsers, SVR was 69%-75% for boceprevir vs. 83-88% for telaprevir. In what we would call partial responders MRK has a different definition, SVR was 40-52% for boceprevir vs. 54-59% for telaprevir. Cross-trial comparisons are always difficult but we believe the totality and consistency of both treatment-experienced and treatment-naïve data give an impression that telaprevir may be more potent.
If there are significant side effects to the Vertex compound that haven’t emerged yet, it could totally negate Vertex’s apparent advantage. But if Vertex’s drug is perceived by doctors as slightly more effective, who does Merck sell its drug to?
Merck R&D head Peter Kim may have some answers to this question. He is going to the liver meeting where he will face lots of questions from Wall Street types about where Merck’s drug will fit in. He needs to rebut the doubts about his company’s drug.
http://blogs.forbes.com/robertlangreth/2010/10/01/vertex-edges-merck-in-first-round-of-hepatitis-c-fight/?boxes=businesschannelsections
By ROBERT LANGRETH
New details of studies of rival hepatitis C drugs from Merck and Vertex Pharmaceuticals were released today in advance of a crucial upcoming meeting of liver specialists at the end of the month in Boston. The drugs, so-called hepatitis C protease inhibitors, represent the first class of agents that directly target the hepatitis C virus. Both have substantially boosted the cure rate in big trials, raising excitement among hepatitis c specialists.
While the drugs haven’t been compared directly, it appears that Vertex’s telaprevir drug is is a nudge better. Unless differences in tolerability and side effects emerge, if both drugs are approved, doctors may look at the data and go with the Vertex drug first because its cure rates appear to be a few percentage points higher.
Here’s what Howard Liang of Leerink Swann wrote in a note today:
“Apples-to-apples” comparison of boceprevir vs. telaprevir in treatment-experienced patients is possible for the first time and appears to favor telaprevir. In prior relapsers, SVR was 69%-75% for boceprevir vs. 83-88% for telaprevir. In what we would call partial responders MRK has a different definition, SVR was 40-52% for boceprevir vs. 54-59% for telaprevir. Cross-trial comparisons are always difficult but we believe the totality and consistency of both treatment-experienced and treatment-naïve data give an impression that telaprevir may be more potent.
If there are significant side effects to the Vertex compound that haven’t emerged yet, it could totally negate Vertex’s apparent advantage. But if Vertex’s drug is perceived by doctors as slightly more effective, who does Merck sell its drug to?
Merck R&D head Peter Kim may have some answers to this question. He is going to the liver meeting where he will face lots of questions from Wall Street types about where Merck’s drug will fit in. He needs to rebut the doubts about his company’s drug.
http://blogs.forbes.com/robertlangreth/2010/10/01/vertex-edges-merck-in-first-round-of-hepatitis-c-fight/?boxes=businesschannelsections
"No trials that I monitored over the years ever mentioned it specifically. Every trial either required treatment naive, or non-response of some sort (either non-SVR or non-RVR) to PEG-interferon. Never did they mention just interferon, always it specified PEGYLATED. One I called and they said pegylated. Maybe I should have actually called more of them and spoken with a live person. "
Yes - I would consider calling and actually talking to someone. The person you spoke with may have simply been repeating what the information said but it's been awhile since non-pegylated interferon was used so perhaps they don't mention it anymore. It's at least worth a shot to pursue it. It doesn't make sense to me to exclude non-pegylated non-responders and include pegylated non-responders. We have a guy on here who did multiple clinical trials over the years and finally got his SVR with Telaprevir. I can bet you he did non-peglyated interferon at one point in this lengthy history with HCV and was still able to get into the Telaprevir non-responder trial. Worth a shot. Good luck with that.
Trish
Yes - I would consider calling and actually talking to someone. The person you spoke with may have simply been repeating what the information said but it's been awhile since non-pegylated interferon was used so perhaps they don't mention it anymore. It's at least worth a shot to pursue it. It doesn't make sense to me to exclude non-pegylated non-responders and include pegylated non-responders. We have a guy on here who did multiple clinical trials over the years and finally got his SVR with Telaprevir. I can bet you he did non-peglyated interferon at one point in this lengthy history with HCV and was still able to get into the Telaprevir non-responder trial. Worth a shot. Good luck with that.
Trish
I wish you luck! And if you have to choose infergen, let your tx be easier than mine and definitely not like Magnum's :) !
"Were you actually told that your treatment with non-pegylated interferon disqualifies you or is it that you just don't see any trials that mention it specifically? "
No trials that I monitored over the years ever mentioned it specifically. Every trial either required treatment naive, or non-response of some sort (either non-SVR or non-RVR) to PEG-interferon. Never did they mention just interferon, always it specified PEGYLATED. One I called and they said pegylated. Maybe I should have actually called more of them and spoken with a live person.
No trials that I monitored over the years ever mentioned it specifically. Every trial either required treatment naive, or non-response of some sort (either non-SVR or non-RVR) to PEG-interferon. Never did they mention just interferon, always it specified PEGYLATED. One I called and they said pegylated. Maybe I should have actually called more of them and spoken with a live person.
Believe only half of what you hear and doubt the other half. At this juncture EVERONE is guessing about the PI releases. Let the chips fall where they may (you can tell I live in Las Vegas), is my belief. Regarding the release of these PI's, every time I ask my contact at Vertex or my Gastro, the reply is always the same. "Not sure".
Magnum
Magnum
Thank you, I appreciate you sharing that info. Yep, you've got a full time job and then some. I limped to the finish line on SOC and I can't not work. Need the money and the insurance. I have a lot of responsibility at home too and the side effects from Infergen worry me. My whites tanked big time with SOC and I hated the effects of Neupogen about as much as the interferon. I'm mulling the options over in my mind, don't need to make any decisions right now but regardless my head has to be right. Actually, if biopsy shows I need to treat again sooner than later I'll see how I respond after 6-8 weeks with Infergen and a higher dose of ribavirin. If I'm not making good progress I'll stop.
Trinity
Trinity
4 months ago my doc returned from some kind of conference in CA on hep C and he was still pretty disappointed with the timelines. I also read those articles, since 2006, and every year the promise there is "another 12-18 months"... So, realistically, I tend to agree with my doc's estimate, nevertheless - it would be awesome if he is wrong. I personally chose not to wait but try to treat as soon as I could for 3 reasons.
First - the longer you have the virus, the harder it is to get rid of. And I suspect I was infected as a newborn in 1976.
Second, HCV is so unpredictable, I've known people who seemed to be able to manage their condition without treatment successfully for a long time and then their health detiorated drammatically within a very short period of time all of a sudden. I didn't want to take chances. I guess, one have to choose which risks he wants to choose - risks of sx or risks of losing your health too soon, too fast.
Third, on a personal level, I have long-term goals, my life is about to get crazy busy on a professional level. So, I chose to undergo tx now, and not to risk my career in case if sx are too harsh.
These post-tx month before you get your SVR or non-SVR verdict are pretty intense :) I am still waiting to know if infergen worked for me. 5 more months. I will post my results then.
First - the longer you have the virus, the harder it is to get rid of. And I suspect I was infected as a newborn in 1976.
Second, HCV is so unpredictable, I've known people who seemed to be able to manage their condition without treatment successfully for a long time and then their health detiorated drammatically within a very short period of time all of a sudden. I didn't want to take chances. I guess, one have to choose which risks he wants to choose - risks of sx or risks of losing your health too soon, too fast.
Third, on a personal level, I have long-term goals, my life is about to get crazy busy on a professional level. So, I chose to undergo tx now, and not to risk my career in case if sx are too harsh.
These post-tx month before you get your SVR or non-SVR verdict are pretty intense :) I am still waiting to know if infergen worked for me. 5 more months. I will post my results then.
I am a stay-at-home mom now, so, no, I was not able to work... unless taking care of too super active 2 year olds (my twins) while my husband was deployed to Iraq doesn't count :) I would say my kids keep me very busy for 12-14 hours a day. And it's not like we sit around and relax, we are really active. I'd say when I did work and didn't have kids, my life was a lot more relaxing :)
I do understand that my "easy" tx on infergen was rather an exception than a rule. My hemoglobin dropped to 8 by the 4th months of being on this drug and only now is slowly getting back up. Other blood values were pretty scary. I remember when my regular PCM saw me she couldn't believe at first that I could make it myself to the office, as my blood values were so low. I lost 30 lbs during treatment. However, my liver doc was against using procrit, he simply managed me within the 8-9 hemoglobin range with riba reduction - my weight allowed it, as even 800 of riba a day was my max dosage as per weight, and I started tx with 1200 daily. So no matter what, even with reduction I was at pretty high riba levels. During last 2 months of tx I experienced some brain fog and heart murmurs - all of that is gone now, 1 month post tx. I am waiting for my PCM appointment to have my heart checked out now, just in case, as some heart conditions run in my family. Other than that - I definitely expected infergen tx to be much harsher than it was.
I do understand that my "easy" tx on infergen was rather an exception than a rule. My hemoglobin dropped to 8 by the 4th months of being on this drug and only now is slowly getting back up. Other blood values were pretty scary. I remember when my regular PCM saw me she couldn't believe at first that I could make it myself to the office, as my blood values were so low. I lost 30 lbs during treatment. However, my liver doc was against using procrit, he simply managed me within the 8-9 hemoglobin range with riba reduction - my weight allowed it, as even 800 of riba a day was my max dosage as per weight, and I started tx with 1200 daily. So no matter what, even with reduction I was at pretty high riba levels. During last 2 months of tx I experienced some brain fog and heart murmurs - all of that is gone now, 1 month post tx. I am waiting for my PCM appointment to have my heart checked out now, just in case, as some heart conditions run in my family. Other than that - I definitely expected infergen tx to be much harsher than it was.
Tired, not typing well
Correction: at this point I don't feel like I've got a whole to to lose.
Correction: at this point I don't feel like I've got a whole to to lose.
"Will we still be alive to have it? Or be too old to have it?"
That's based on degree of liver damage. I'm a stage a late state 3 and I did 72 wks of SOC to no avail except maybe slowing down the fibrosis. It wouldn't be prudent for me to treat with SOC again and except different results. You've never treated with pegylated interferon so you really don't know how you'll respond. If it looks like the FDA is dragging their feet approving the PI's by next year and biopsy shows fibrosis is advancing I will consider Infergen. My job is very demanding to and quite honestly I don't how the hell I'm going to do it but I'll do it even with a 25 percent chance of SVR. Of course I want better odds but I also don't want to transition over to full blown cirrhosis. This whole hepc thing is friggin balancing act, a game of chance and at this point I don't feel like I've got whole to loose. Maybe an SVR or only stopping the fibrosis from advancing, to me either way it's a win win.
Trinity
That's based on degree of liver damage. I'm a stage a late state 3 and I did 72 wks of SOC to no avail except maybe slowing down the fibrosis. It wouldn't be prudent for me to treat with SOC again and except different results. You've never treated with pegylated interferon so you really don't know how you'll respond. If it looks like the FDA is dragging their feet approving the PI's by next year and biopsy shows fibrosis is advancing I will consider Infergen. My job is very demanding to and quite honestly I don't how the hell I'm going to do it but I'll do it even with a 25 percent chance of SVR. Of course I want better odds but I also don't want to transition over to full blown cirrhosis. This whole hepc thing is friggin balancing act, a game of chance and at this point I don't feel like I've got whole to loose. Maybe an SVR or only stopping the fibrosis from advancing, to me either way it's a win win.
Trinity
Were you actually told that your treatment with non-pegylated interferon disqualifies you or is it that you just don't see any trials that mention it specifically?
Check this out . Combination therapy with both protease and polymerase inhibitors from Vertex-- http://files.shareholder.com/downloads/VRTX/0x0x365624/4005613a-8d1a-4876-843d-91a88520ee71/VRTX_News_2010_4_15_Webcasts.pdf
I wonder how long before their polymerase inhibitor will be available. It would be real nice to get into a clinical trial at the next stage.
I wonder how long before their polymerase inhibitor will be available. It would be real nice to get into a clinical trial at the next stage.
I would want to kill the damned thing. But I am realistic. The probability of SVR after 48 weeks RBV & peg-IFN for genotype I previous non-responders is only 10%. So likely, I would fail treatment anyway, unless I extended treatment to 96 weeks (24 months), which would be difficult to handle.
"At best, we're looking at perhaps 1 more year."
Then maybe it'll be better to wait it out. I've waited this long. I suppose another year is OK.
"Do you mean consensus interferon when you say non pegylated interferon?"
In many of the Telaprivir and other trials, the requirement for inclusion was failed treatment with pegylated interferon, or treatment naive. In my case, the interferon I had was not pegylated. This was back in '99-'00. I would have sought treatment again with pegylated interferon except that after further research, I found that with genotype 1 and previously failed RBV & IFN treatment, I would only stand a 10% chance of SVR.
At that point, I did some math with my viral load levels (using an exponential decay model) and determined that 20 - 22 months or so of RBV & peg IFN therapy would reduce the viral load below 1 single particle to a 50% probability. (I'm a math major.) This is provided my hematocrit would hold up.
I held up pretty well during the previous RBV & IFN treatment, working full-time in a demanding programming job. The only thing where I slowed down was that instead of taking a wilderness backpack hunting trip that year, I went on a wilderness horseback hunting trip that year. So, I figured I was strong enough to handle 22 months, especially if I took off some time from work and gradually cut back on activity. I worked as a consultant, contractor or temp doing programming.
I was starting to provide for the long period of treatment, even if I had to go to several doctors. But then, I read about protease inhibitors (VX-950) being very effective against HCV. So, I decided to forgo my plans for extended treatment, and wait a few years until it came out. Also, if the treatment failed, I did not want to create a more resistant strain of virus. Well, I've been waiting and waiting and waiting. Every year, it'll be next year.
Each year, I have to make a decision whether to get the pegylated treatment plan or wait for the protease inhibitor to come out. If I did the Ribavirin & peg interferon only, I'd arrange for up to 48 months of treatment. I want to kill the damned thing. I'm 58 now. Will I even be able to handle the 48 months? Better do it soon before I get much older.
But if it'll only be another year, maybe it's worth waiting. But it's only been another year for the last 4 years, since 2006.
Plus, there are polymerase inhibitors in development also -- http://www.outsourcing-pharma.com/Preclinical-Research/Roche-s-oral-polymerase-inhibitor-exhibits-hep-C-efficacy. Clinical trials Filibuvir -- http://www.clinicaltrials.gov/ct2/show/NCT00987337?term=polymerase+inhibitor&rank=10
In the long term there will be "quadruple therapy", with both protease and polymerase inhibitors, which promises to be very effective. The question is how long. Will we still be alive to have it? Or be too old to have it?
Then maybe it'll be better to wait it out. I've waited this long. I suppose another year is OK.
"Do you mean consensus interferon when you say non pegylated interferon?"
In many of the Telaprivir and other trials, the requirement for inclusion was failed treatment with pegylated interferon, or treatment naive. In my case, the interferon I had was not pegylated. This was back in '99-'00. I would have sought treatment again with pegylated interferon except that after further research, I found that with genotype 1 and previously failed RBV & IFN treatment, I would only stand a 10% chance of SVR.
At that point, I did some math with my viral load levels (using an exponential decay model) and determined that 20 - 22 months or so of RBV & peg IFN therapy would reduce the viral load below 1 single particle to a 50% probability. (I'm a math major.) This is provided my hematocrit would hold up.
I held up pretty well during the previous RBV & IFN treatment, working full-time in a demanding programming job. The only thing where I slowed down was that instead of taking a wilderness backpack hunting trip that year, I went on a wilderness horseback hunting trip that year. So, I figured I was strong enough to handle 22 months, especially if I took off some time from work and gradually cut back on activity. I worked as a consultant, contractor or temp doing programming.
I was starting to provide for the long period of treatment, even if I had to go to several doctors. But then, I read about protease inhibitors (VX-950) being very effective against HCV. So, I decided to forgo my plans for extended treatment, and wait a few years until it came out. Also, if the treatment failed, I did not want to create a more resistant strain of virus. Well, I've been waiting and waiting and waiting. Every year, it'll be next year.
Each year, I have to make a decision whether to get the pegylated treatment plan or wait for the protease inhibitor to come out. If I did the Ribavirin & peg interferon only, I'd arrange for up to 48 months of treatment. I want to kill the damned thing. I'm 58 now. Will I even be able to handle the 48 months? Better do it soon before I get much older.
But if it'll only be another year, maybe it's worth waiting. But it's only been another year for the last 4 years, since 2006.
Plus, there are polymerase inhibitors in development also -- http://www.outsourcing-pharma.com/Preclinical-Research/Roche-s-oral-polymerase-inhibitor-exhibits-hep-C-efficacy. Clinical trials Filibuvir -- http://www.clinicaltrials.gov/ct2/show/NCT00987337?term=polymerase+inhibitor&rank=10
In the long term there will be "quadruple therapy", with both protease and polymerase inhibitors, which promises to be very effective. The question is how long. Will we still be alive to have it? Or be too old to have it?
Any use of these lousey meds should be taken with the intent to be successful, not to fail. These are powerful and can have long-term after effects. I suppose that a person could go into treat with less than full inent but to me it doesn't make a lot of sense. With an experienced doc there are modifications that could be may to enhance chances of success. Or, just wait until better stuff comes along - not in a trial setting.
"Unless a person failed treatment many years ago with non-peg the chances are slim that a first attempt would be with anything other than peg."
That's me.
That's me.
I have coverage, both through one of my employers and the VA. My concern is access to effective treatment, at all, insurance coverage or not. It seems that the only way to get effective treatment is via clinical trials. Too bad one can't obtain the drugs in Mexico free from U.S. government restriction. Too bad there's not a black market.
Time marches on. We're all getting older and the damage is piling up. Life is slipping away. It takes decades for drugs to go through all the government mandated trials. There's got to be a way around the system. Maybe there are other countries where they would be more readily available. I'd pay cash money.
Here's another drug coming up, polymerase inhibitor -- http://www.clinicaltrials.gov/ct2/show/NCT01180790?term=hepatitis+c+phase+2&recr=Open&rank=38. It would be nice to be able to add this to the mix, especially for us non-responders. Unfortunately, these trials are only open to the treatment naive. Likely, it'll be at least 10 years before this ever hits the market.
Here's a whole mess of other drugs under development. I wonder how long it's going to take these to hit the market. Let's hope we all hold out for another 10 years. http://www.hivandhepatitis.com/hep_c/hepc_news_alter.html#stat
Time marches on. We're all getting older and the damage is piling up. Life is slipping away. It takes decades for drugs to go through all the government mandated trials. There's got to be a way around the system. Maybe there are other countries where they would be more readily available. I'd pay cash money.
Here's another drug coming up, polymerase inhibitor -- http://www.clinicaltrials.gov/ct2/show/NCT01180790?term=hepatitis+c+phase+2&recr=Open&rank=38. It would be nice to be able to add this to the mix, especially for us non-responders. Unfortunately, these trials are only open to the treatment naive. Likely, it'll be at least 10 years before this ever hits the market.
Here's a whole mess of other drugs under development. I wonder how long it's going to take these to hit the market. Let's hope we all hold out for another 10 years. http://www.hivandhepatitis.com/hep_c/hepc_news_alter.html#stat
Unless a person failed treatment many years ago with non-peg the chances are slim that a first attempt would be with anything other than peg.
Hey Trin,
Yes geno 2"s do really well with the PI's so I was more than disappointed when my doc told me that the PI's will not be approved for Geno 2's. I asked him if he was sure and he said yes. Would they rather pay for extended doctor visits, treatments and possibly liver transplants. It is because Geno 2's are supposedly easier to tx. Well I am here to say that that is not always true. Anyway I am upset so.......
Yes geno 2"s do really well with the PI's so I was more than disappointed when my doc told me that the PI's will not be approved for Geno 2's. I asked him if he was sure and he said yes. Would they rather pay for extended doctor visits, treatments and possibly liver transplants. It is because Geno 2's are supposedly easier to tx. Well I am here to say that that is not always true. Anyway I am upset so.......
I think your doc is incorrect when he states 2 to 3 years at best for new PIs. Everything I have read says its going to be 15 to 18 months at most.
Off topic, but were you able to work while undergoing treatment with Infergen? As you know I haven't ruled Infergen out completely if the PI's get stalled and biopsy shows fibrosis has advanced.
Trinity
Trinity
That was one of the questions I asked my doc when we were making decision wether to switch to infergen when I didn't respond to pegasys. He told me that the way things are going now, we will not get the new PIs approved for another 2-3 years (at best), and that even if I fail infergen tx, that would not disqualify me from the new drugs tx in the future. As for clinical trials - I am not too fond of them. I prefer my insurance to cover the treatment, not to take extra risks with trials. However, for someone who is more open or doesn't have healthcare coverage, trials would be an excellent option, I agree.
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