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Good News/Bad News from AASLD
I've just returned from AASLD and was able to learn some good things and bad things. The good news is that both the Schering protease and Telaprevir are doing rather well with treatment naive and relapsers. The bad news is that patients who have treated before and are null responders (didn't have a 2 log drop by 12 weeks) will not respond to the protease inhibitors. A number of the hepatologists talked about this, among them Drs. Sulkowski, Shiffman, Terrault and Zezeum....all very well respected. If a patient had enough viral load checks, complied with treatment and didn't miss injections or ribavirin, had no dose reductions, and didn't have at least a 2 log drop by week 12, they are now considered interferon resistant. The combination of SOC and protease will not be enough to overcome that resistance. They feel that these patients will need combinations of protease and polymerase and that these are about 10 years out. I, for one, as a non-responder, is really bummed about this.
The other lousy news is from the HALT C trial regarding maintenance therapy. Unless a person can keep their viral load undetected (in other words, they relapse without interferon) it does not work. If the doctor can get them to undetected again and play with the dose of Peg to keep them at that level, it probably will work. HALT C showed no improvement in fibrosis scores, HCC, ascites, from maintenance in virus detected people. The only benefit was a reduction in the incidence of varices.
This was not a happy year for me at AASLD.
The other lousy news is from the HALT C trial regarding maintenance therapy. Unless a person can keep their viral load undetected (in other words, they relapse without interferon) it does not work. If the doctor can get them to undetected again and play with the dose of Peg to keep them at that level, it probably will work. HALT C showed no improvement in fibrosis scores, HCC, ascites, from maintenance in virus detected people. The only benefit was a reduction in the incidence of varices.
This was not a happy year for me at AASLD.
Susie,
From your comments I assume that you didn't get a 2log drop on SOC tx (I've heard so many criteria for non-responder). I'm really sorry for how you must feel.
Hopefully your grade and inflammation are low. What's your stats?
Were these presentations made by these docs that you attended at AASLD?
Thanks for attending and reporting back to us.
Mike
From your comments I assume that you didn't get a 2log drop on SOC tx (I've heard so many criteria for non-responder). I'm really sorry for how you must feel.
Hopefully your grade and inflammation are low. What's your stats?
Were these presentations made by these docs that you attended at AASLD?
Thanks for attending and reporting back to us.
Mike
I've come close to a 2 log drop, but never actually achieved that. I was diagnosed in 1992 and had cirrhosis at that time. I was really counting on the telaprevir. But I'll get over this, I always do. Thanks for your interest in my situation.
Susie,
I, too, am disappointed to hear this news. I'm in the same boat.... I was hoping that the maintenance study (HALT-C) was going to show better results. I don't really like the idea of having to go through 4 drugs w/Interferon, Riba, Polymerase and Protease inhibitors as I feel like the sides would be unbearable for most of us to have to deal with. My body has already endured 9 treatments and I am just tired... I was really hoping for some sort of low dose maintenance type of thing because I figured I could just manage this disease like diabetics do with insulin. I wish there had been better news..., I'm with you though, we'll get over it together, okay? Susan (another Sus)
I, too, am disappointed to hear this news. I'm in the same boat.... I was hoping that the maintenance study (HALT-C) was going to show better results. I don't really like the idea of having to go through 4 drugs w/Interferon, Riba, Polymerase and Protease inhibitors as I feel like the sides would be unbearable for most of us to have to deal with. My body has already endured 9 treatments and I am just tired... I was really hoping for some sort of low dose maintenance type of thing because I figured I could just manage this disease like diabetics do with insulin. I wish there had been better news..., I'm with you though, we'll get over it together, okay? Susan (another Sus)
Sorry to hear the news. I received my 8 week labs today and had a 1/2 log drop from the beginning of treatment. Then I came home and read this. Not one of the best days. I guess it's good to know your not alone but it would sure be nice to hear something a little more encouraging from them.
I was going to wait for Telaprivir to treat but my doctor convinced me to treat now. I wonder now if I had waited would it have been different. I'll never know for sure. We can pray for a miracle. You never know something may come along sooner than we think.
I was going to wait for Telaprivir to treat but my doctor convinced me to treat now. I wonder now if I had waited would it have been different. I'll never know for sure. We can pray for a miracle. You never know something may come along sooner than we think.
thanks for the update. really sorry for the bad news for you. if you are the susie that has the other HCV forum you will be fine as i have been going to that site for over a year now and you are a very strong and good person. if i was you i would still try one of the PI's when approved and if not unde at 4 weeks stop. what do you have to lose by giving it a try? right now alot of what docs say are still guesswork. no one really knows. if you are the susie i'm thinking of you will be cured someday, you have helped to many people not to be paid back with something good. good luck and god bless
so sorry to hear this new for you.
not to spread false hope, but it was encouraging to read of the discovery of the role of the genome proj. regarding activin suppression.
there was another new sulfa drug that England's been working on, dr.David Ward maybe, sheesh mind is a sieve... have to go find it again now. both these approaches deal with reversal of fibrosis, which would be the other approach, to find something that, in spite of viral load or not will repress or reverse the process of fibrosis.
I would think one day, they'll do both simultaneously, and that the race will be one as to how to turn the gene off (there are four of them).
the one in england is available now though and may be a stop gap you could press for, even if on a transplant list I'd still check it out.
will try to find that link for you. hope it helps!
not to spread false hope, but it was encouraging to read of the discovery of the role of the genome proj. regarding activin suppression.
there was another new sulfa drug that England's been working on, dr.David Ward maybe, sheesh mind is a sieve... have to go find it again now. both these approaches deal with reversal of fibrosis, which would be the other approach, to find something that, in spite of viral load or not will repress or reverse the process of fibrosis.
I would think one day, they'll do both simultaneously, and that the race will be one as to how to turn the gene off (there are four of them).
the one in england is available now though and may be a stop gap you could press for, even if on a transplant list I'd still check it out.
will try to find that link for you. hope it helps!
http://64.233.167.104/search?q=cache:Klfsamq6jiIJ:www.ncl.ac.uk/icm/people/profile/derek.mann+newcastle+university+liver+fibrosis&hl=en&ct=clnk&cd=2&gl=us
getting there
getting there
Hey Susie - fancy meeting a nice girl like you in a hepC forum. Okay, so you know how we're given all these contradictory stats and anecdotal stuff - I just came across an article from Japan about a study on HCC recurrence. Apparently, patients who are cured of HCC have a significantly lower recurrence rate, and significantly increased survival when treated with 24 months SOC dose monotherapy IFN-a post-HCC cure. The hits just keep comin in.
well finally, this is what I get for not earmarking everything of importance, someone just posted this a couple days ago, but since I can't take sulfa drugs I hadn't flagged it.
it may help you, especially if you don't drink, even though they were trying it on drinkers, make sense that it would help non-drinkers even more.
http://news.bbc.co.uk/2/hi/health/5382172.stm
it may help you, especially if you don't drink, even though they were trying it on drinkers, make sense that it would help non-drinkers even more.
http://news.bbc.co.uk/2/hi/health/5382172.stm
Hey Susie, must have missed you there...took Amanda to the meetings as well... I actually did not hear the news about the 2 log drop and the PI's....As a matter of fact, I really think that if Amanda had triple therapy in Prove3 she would be SVR right now...and she is a perfect example of a previos non-responder...so she never even had a 1 log drop, was in Prove 3/no riba group...cleared between week 1 and 2 and had breakthrough at week 20...so there is hope and if you can try the triple therapy, I say go for it!!!!
Sorry I missed you there..
Jodi
Sorry I missed you there..
Jodi
Hi.......I've been out of town and I am not well read on the results of the trial but I want to throw out a few concepts and see how they resonate. You see.....I think there was good news offered.
1) The results of Telaprevir may be lower than expected or desired but they still represent a vast improvement over current TX/SOC;
a) Treatment times cut in half
b) Lower relapse rates
c) dramatically higher RVR rates
d) The ability to at least try a treatment and if you don't RVR one can quit treatment. EVEN in FAILURE of treatment we see an improvement.
e) There has not been any evidence so far of long term toxicity issues. Rather, so far those (the handfull we've seen at this board) who treated....even with severe sides during treatment have had a good even great recovery.
f) There still looms the possibility that we may see proof that this compound may have higher cure rates on the prior treatment failures (in the Prove 3 trial) than Boceprevir; still way too early to make a call on that but several Prove 3's here seem to have achieved RVR's quite early and were able to maintain them. This bodes well as a predictor of SVR. It's true that this has little to do with the results of AASLD but keep the results in perspective
g) In a month or two we may see the commencement of PROVE 4 (Phase 3 trial) and we may also see the shape and scope of the trials. I think the HCV and investment community would love to see what the compound can provide if full dosage and full term treatment as allowed (via the use of rescue drugs).
f) Also keep in mind.....if any improvements can be made in countering the sides of Telaprevir we won't see them in the Prove 1 results. Improvements may be seen in Prove 3 results. Further refinements may also be seen in the criteria seen in the upcoming Phase 3 trials. (another assumption here too; I'm assuming they will get the greenlight to move to Phase 3)
g) Straying from the concept of the AASLD..... but we've seen no evidence provided in the conference which suggests that the compound won't proceed to Phase 3 trials. If that happens we will see the culmination of what this compound may do. This could entail shorter treatment times (might some be able to treat in less than the "12 and 12 treatment"), a potentially lower dropout rate (due to rescue drugs and greater confidence in the treatment)
Regarding Boceprevir; Many of the same issues will pertain to this compound as well. The trial id still early Phase 2....... there will be improvements during the duration of Phase 2. Once again the real proof of what the drug may do won't be till Phase 3. I continue to feel that both drug companies may shelter the real data so as to keep their competitors in the dark. That will also keep us in the dark along the way but I'll assert that scant information does not equal proof of poor performance. Now we have at least another (and in fact there are several more) possible alternatives to Telaprevir.
Alinia offers a possibility of a drug which is already approved, low in price and while it may be too early to have solid SVR rates we can be hopeful that we may soon have a third drug which can be combined with current SOC. This drug may increase RVR & SVR rates. It seems to be cheap and largely free of troublesome side effects. It may also loom as a drug which could also raise the efficacy rates of the Telaprevir or Boceprevir treatments should they be approved. Even people who have failed in the past can possibly soon treat and with a greater expectation of a better chance of clearing. Thsi may be very important for people with advanced liver disease.
This is a long enough post...... but there are other new compounds which look promising. We may have more assurance that one will make it through approval. In this, I think that the future looks far brighter than it did a year ago.
If there have been failures...... or disappointments I would still suggest that even in failure the drug companies end up with a better understanding of the virus. We already have a 40-50% SVR rate. The treatment time is about to decrease, the SVR rate is soon to increase and lots of new treatments are in the pipeline.
I understand that it's an expected result; things may not be as great as we had hoped for but keep things in perspective. The half empty glass just filled up another 25%.
best,
Willy
1) The results of Telaprevir may be lower than expected or desired but they still represent a vast improvement over current TX/SOC;
a) Treatment times cut in half
b) Lower relapse rates
c) dramatically higher RVR rates
d) The ability to at least try a treatment and if you don't RVR one can quit treatment. EVEN in FAILURE of treatment we see an improvement.
e) There has not been any evidence so far of long term toxicity issues. Rather, so far those (the handfull we've seen at this board) who treated....even with severe sides during treatment have had a good even great recovery.
f) There still looms the possibility that we may see proof that this compound may have higher cure rates on the prior treatment failures (in the Prove 3 trial) than Boceprevir; still way too early to make a call on that but several Prove 3's here seem to have achieved RVR's quite early and were able to maintain them. This bodes well as a predictor of SVR. It's true that this has little to do with the results of AASLD but keep the results in perspective
g) In a month or two we may see the commencement of PROVE 4 (Phase 3 trial) and we may also see the shape and scope of the trials. I think the HCV and investment community would love to see what the compound can provide if full dosage and full term treatment as allowed (via the use of rescue drugs).
f) Also keep in mind.....if any improvements can be made in countering the sides of Telaprevir we won't see them in the Prove 1 results. Improvements may be seen in Prove 3 results. Further refinements may also be seen in the criteria seen in the upcoming Phase 3 trials. (another assumption here too; I'm assuming they will get the greenlight to move to Phase 3)
g) Straying from the concept of the AASLD..... but we've seen no evidence provided in the conference which suggests that the compound won't proceed to Phase 3 trials. If that happens we will see the culmination of what this compound may do. This could entail shorter treatment times (might some be able to treat in less than the "12 and 12 treatment"), a potentially lower dropout rate (due to rescue drugs and greater confidence in the treatment)
Regarding Boceprevir; Many of the same issues will pertain to this compound as well. The trial id still early Phase 2....... there will be improvements during the duration of Phase 2. Once again the real proof of what the drug may do won't be till Phase 3. I continue to feel that both drug companies may shelter the real data so as to keep their competitors in the dark. That will also keep us in the dark along the way but I'll assert that scant information does not equal proof of poor performance. Now we have at least another (and in fact there are several more) possible alternatives to Telaprevir.
Alinia offers a possibility of a drug which is already approved, low in price and while it may be too early to have solid SVR rates we can be hopeful that we may soon have a third drug which can be combined with current SOC. This drug may increase RVR & SVR rates. It seems to be cheap and largely free of troublesome side effects. It may also loom as a drug which could also raise the efficacy rates of the Telaprevir or Boceprevir treatments should they be approved. Even people who have failed in the past can possibly soon treat and with a greater expectation of a better chance of clearing. Thsi may be very important for people with advanced liver disease.
This is a long enough post...... but there are other new compounds which look promising. We may have more assurance that one will make it through approval. In this, I think that the future looks far brighter than it did a year ago.
If there have been failures...... or disappointments I would still suggest that even in failure the drug companies end up with a better understanding of the virus. We already have a 40-50% SVR rate. The treatment time is about to decrease, the SVR rate is soon to increase and lots of new treatments are in the pipeline.
I understand that it's an expected result; things may not be as great as we had hoped for but keep things in perspective. The half empty glass just filled up another 25%.
best,
Willy
I am interested if the info you mentioned about non-responders (to SOC) not having a chance with protease inhibitors has been released to the public yet?
I have heard no mention of prove 3 data from Vertex yet. Prove 3 started dosing non-responders a little over 24 weeks ago and the study is not over yet.
Is interim data available somewhere? Or is all this talk just talk?
Cheese
I have heard no mention of prove 3 data from Vertex yet. Prove 3 started dosing non-responders a little over 24 weeks ago and the study is not over yet.
Is interim data available somewhere? Or is all this talk just talk?
Cheese
Wow, I guess it's time for me to rethink my paradigm and sit down in again with my big brain doc. My last biopsy took me from stage 2 to stage 3, but Doc Scott convinced me to wait until telaprevir was approved to tx again. Now I'm not sure I'm a classic null responder, I had a 2 log drop at week 12, but virus spiked back 10 fold at 24 weeks. When I think real hard, I remember Doc saying I was inteferon resistant...not a memory I'm glad to have..in light of your news.
Mutha freakin apricots, this changes everything. I'm gonna go cry for a bit and then figure out a new plan. Things will have to get better tomorrow.
Willow
Mutha freakin apricots, this changes everything. I'm gonna go cry for a bit and then figure out a new plan. Things will have to get better tomorrow.
Willow
Sounds like by the definition given previously, you're a responder who had a viral breakthrough -- as opposed to a non-responder or relapser. That sub group was not addressed in Susie's post, so no reason to be discouraged. In fact, I'm sure the whole story is more complex than stated, and hopefully more positive -- at least for the non-responders. Keep in mind that previous non-responders have responded with variations of SOC, and maybe some variation of triple tx -- still not trialed -- will be the winning combination.
All the best,
-- Jim
All the best,
-- Jim
Will you marry me? Well, accept my thanks anyway for the comfort. I'm just rattled because I distinctly remember the doc tellin me that I was interferon resistant. But you are right, it will take time for the data to be sorted out. Come to think of it, aren't we all interferon resistant? I mean, who in their right mind would not resist it? I say let's mount a campaign and eradicate interferon from the planet, right after we find the FDA fool who approved it as tx for the virus and force that fool to watch "Judge Judy" daily until common sense returns.
My reticence about being dang sure a person needs to treat and is really ready to tx was a prophetic notion, I think. I know you share a version of the caution too. If only I knew then what I know now....but how to make sure about something like interferon? I keep remembering the absolutely gawdawful movie the gyno made me watch before my first child was born....simply because I had stated I wished to try natural childbirth. At the time, the movie was a major annoyance, well, except for my husband blanching white and excusing himself for a smoke...and I popped out the most beautiful baby au natural. Too bad I did not have such luck with the ole interferon and riba...and perhaps with this news from AASLD, someone will create protocols a bit more stringent now, at least until a combo of PI's is approved and tested.
To be a null responder, or interferon resistant now has a bigger price tag...dang...just when I was getting used to the usual run of the mill long term effects.
I'm a bit bitter right now...late in the evening like this is probably a good time for it. Tomorrow is another day...great day for a new plan. As soon as I figure out what it is. Thanks, jmjm
My reticence about being dang sure a person needs to treat and is really ready to tx was a prophetic notion, I think. I know you share a version of the caution too. If only I knew then what I know now....but how to make sure about something like interferon? I keep remembering the absolutely gawdawful movie the gyno made me watch before my first child was born....simply because I had stated I wished to try natural childbirth. At the time, the movie was a major annoyance, well, except for my husband blanching white and excusing himself for a smoke...and I popped out the most beautiful baby au natural. Too bad I did not have such luck with the ole interferon and riba...and perhaps with this news from AASLD, someone will create protocols a bit more stringent now, at least until a combo of PI's is approved and tested.
To be a null responder, or interferon resistant now has a bigger price tag...dang...just when I was getting used to the usual run of the mill long term effects.
I'm a bit bitter right now...late in the evening like this is probably a good time for it. Tomorrow is another day...great day for a new plan. As soon as I figure out what it is. Thanks, jmjm
Susy wrote; "If a patient had enough viral load checks, complied with treatment and didn't miss injections or ribavirin, had no dose reductions, and didn't have at least a 2 log drop by week 12, they are now considered interferon resistant"
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I'm not challenging this. I think that it may very well be true. The question however is; what will be the ultimate RVR rate (and SVR rate) for prior nonresponders in protease inhibitor trials? I don't think we know the answer yet for Vertex although if one based the results on Andiamo or Miked one would not be pessimistic; rather the opposite. They are in Prove 3 (and therefore past treatment failures) who cleared in one and two weeks respectively (or pretty close to thereabouts). Another trial participant, dmhrdh was able to clear, but not as quickly partially possibly due to a reduction in ribiviren. This is an example of a case where rescue drugs may have been of some assistance. Until we are able to see the results of a complete optimal treatment we cannot expect optimal results. I'm not positve that the Boceprevir trials were the optimal results that one can expect in treating treatment failures. They also may not reflect what we can expect from the Telaprevir trials. In these trials so far it appears that there have been several members of this board who attained (and maintained) RVR, at least 3 who have cleared by week 12. As time goes on we will have more results. The real question is the issue of SVR. So far it looks a long ways from discouraging, at least to me.
I don't recall......but don't about 80-90% of those who stay on treatment (SOC and TVR) end up with a RVR? With standard SOC during the trials I believe that about 11% (the control arm) on SOC hit an RVR. Yes.....that still leaves out some people but it is a much smaller group, no? The quote above may pertain to that group but even so....... I don't believe that any of them were issued rescue drugs. Would the results have been the same if they had been allowed the use of some of these drugs (for instance Procrit or Neupogen)?
I just happen to believe that it is better to dwell on the positives....and there are more than a few.
Willy
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I'm not challenging this. I think that it may very well be true. The question however is; what will be the ultimate RVR rate (and SVR rate) for prior nonresponders in protease inhibitor trials? I don't think we know the answer yet for Vertex although if one based the results on Andiamo or Miked one would not be pessimistic; rather the opposite. They are in Prove 3 (and therefore past treatment failures) who cleared in one and two weeks respectively (or pretty close to thereabouts). Another trial participant, dmhrdh was able to clear, but not as quickly partially possibly due to a reduction in ribiviren. This is an example of a case where rescue drugs may have been of some assistance. Until we are able to see the results of a complete optimal treatment we cannot expect optimal results. I'm not positve that the Boceprevir trials were the optimal results that one can expect in treating treatment failures. They also may not reflect what we can expect from the Telaprevir trials. In these trials so far it appears that there have been several members of this board who attained (and maintained) RVR, at least 3 who have cleared by week 12. As time goes on we will have more results. The real question is the issue of SVR. So far it looks a long ways from discouraging, at least to me.
I don't recall......but don't about 80-90% of those who stay on treatment (SOC and TVR) end up with a RVR? With standard SOC during the trials I believe that about 11% (the control arm) on SOC hit an RVR. Yes.....that still leaves out some people but it is a much smaller group, no? The quote above may pertain to that group but even so....... I don't believe that any of them were issued rescue drugs. Would the results have been the same if they had been allowed the use of some of these drugs (for instance Procrit or Neupogen)?
I just happen to believe that it is better to dwell on the positives....and there are more than a few.
Willy
I posted this on another thread, very preliminary stuff, but it does seem to be a different direction
"Conatus Pharmaceuticals Reports Positive Results of CTS-1027 in Multiple Preclinical Studies of Liver Disease
SAN DIEGO, November 05, 2007 /PRNewswire/ -- Conatus Pharmaceuticals Inc. today reported positive preclinical results on its lead compound, CTS-1027 in multiple models of hepatitis, an inflammatory liver disease. The results were presented in a poster session today at the American Association for the Study of Liver Diseases (AASLD) in Boston, MA.
CTS-1027 significantly reduced liver damage following oral administration in four different preclinical models of liver injury. CTS-1027 markedly reduced aminotransferase (ALT) activity and improved survival and liver histology in the TNFalpha/Gln model. CTS-1027 was equally effective dosed at the same time as the insult or post-insult in the LPS/Gln model. CTS-1027 significantly reduced ALT activity in the Fas and Con A models. Dosing was well below or equivalent to exposure levels previously tolerated in human clinical studies.
"CTS-1027 represents a potential new and exciting approach to treat patients infected with Hepatitis C Virus (HCV), and in the treatment of other liver diseases. Our initial goal for the development of CTS-1027 is to establish safety and efficacy in patients infected with HCV who have failed or can not tolerate standard of care," stated Alfred Spada, Ph.D., SVP Research and Development. "We plan to initiate a Phase 2 clinical trial within the next few months."
CTS-1027 is an oral, small molecule, matrix metalloproteinase (MMP) inhibitor under development for chronic use to protect the liver from damage due to a variety of insults including virus infection, obesity, alcohol use, and autoimmune diseases. Preclinical studies demonstrate strong efficacy in multiple models of liver disease. In previous clinical trials in other therapeutic areas, CTS-1027 was chronically administered to over 500 people, some for over 18 months.
Matrix metalloproteinases (MMPs) are a well studied family of proteolytic enzymes. In the liver, as in other solid organs, MMPs play a key role in maintaining the integrity of the extracellular matrix. Excessive MMP activity has been demonstrated to occur in the liver in response to a variety of acute and chronic insults. This results in the loss of scaffolding that maintains the normal architecture of the liver and the recruitment and activation of inflammatory cells that perpetuate liver damage. In addition, important cytokines in the progression of liver damage, such as TGF-beta, stimulate the expression of MMPs from hepatic stellate cells, the main cell type involved in the pathology of fibrosis. MMPs are also well recognized to play an important and direct role in regulating inflammation. These dual activities of tissue remodeling and modulating inflammatory networks make MMPs an attractive target in the setting of acute and chronic liver disease.
Conatus Pharmaceuticals Inc. is a privately-held specialty pharmaceutical company engaged in the development of innovative human therapeutics to treat liver disease. Chronic liver disease affects millions of people worldwide and can be caused by many different conditions or "insults" to the liver including Hepatitis C and other viral infections, obesity, chronic alcohol abuse or autoimmune diseases. Conatus was founded by the executive management team of Idun Pharmaceuticals in July 2005 following the successful sale of Idun to Pfizer.
http://www.conatuspharma.com
CONTACT: Steven J. Mento, Ph.D., President and CEO, +1-858-457-7222,, or Alfred P. Spada, Ph.D., Sr. VP R & D,+1-858-457-7223, , both of Conatus PharmaceuticalsInc. ***@**** ***@**** "
"Conatus Pharmaceuticals Reports Positive Results of CTS-1027 in Multiple Preclinical Studies of Liver Disease
SAN DIEGO, November 05, 2007 /PRNewswire/ -- Conatus Pharmaceuticals Inc. today reported positive preclinical results on its lead compound, CTS-1027 in multiple models of hepatitis, an inflammatory liver disease. The results were presented in a poster session today at the American Association for the Study of Liver Diseases (AASLD) in Boston, MA.
CTS-1027 significantly reduced liver damage following oral administration in four different preclinical models of liver injury. CTS-1027 markedly reduced aminotransferase (ALT) activity and improved survival and liver histology in the TNFalpha/Gln model. CTS-1027 was equally effective dosed at the same time as the insult or post-insult in the LPS/Gln model. CTS-1027 significantly reduced ALT activity in the Fas and Con A models. Dosing was well below or equivalent to exposure levels previously tolerated in human clinical studies.
"CTS-1027 represents a potential new and exciting approach to treat patients infected with Hepatitis C Virus (HCV), and in the treatment of other liver diseases. Our initial goal for the development of CTS-1027 is to establish safety and efficacy in patients infected with HCV who have failed or can not tolerate standard of care," stated Alfred Spada, Ph.D., SVP Research and Development. "We plan to initiate a Phase 2 clinical trial within the next few months."
CTS-1027 is an oral, small molecule, matrix metalloproteinase (MMP) inhibitor under development for chronic use to protect the liver from damage due to a variety of insults including virus infection, obesity, alcohol use, and autoimmune diseases. Preclinical studies demonstrate strong efficacy in multiple models of liver disease. In previous clinical trials in other therapeutic areas, CTS-1027 was chronically administered to over 500 people, some for over 18 months.
Matrix metalloproteinases (MMPs) are a well studied family of proteolytic enzymes. In the liver, as in other solid organs, MMPs play a key role in maintaining the integrity of the extracellular matrix. Excessive MMP activity has been demonstrated to occur in the liver in response to a variety of acute and chronic insults. This results in the loss of scaffolding that maintains the normal architecture of the liver and the recruitment and activation of inflammatory cells that perpetuate liver damage. In addition, important cytokines in the progression of liver damage, such as TGF-beta, stimulate the expression of MMPs from hepatic stellate cells, the main cell type involved in the pathology of fibrosis. MMPs are also well recognized to play an important and direct role in regulating inflammation. These dual activities of tissue remodeling and modulating inflammatory networks make MMPs an attractive target in the setting of acute and chronic liver disease.
Conatus Pharmaceuticals Inc. is a privately-held specialty pharmaceutical company engaged in the development of innovative human therapeutics to treat liver disease. Chronic liver disease affects millions of people worldwide and can be caused by many different conditions or "insults" to the liver including Hepatitis C and other viral infections, obesity, chronic alcohol abuse or autoimmune diseases. Conatus was founded by the executive management team of Idun Pharmaceuticals in July 2005 following the successful sale of Idun to Pfizer.
http://www.conatuspharma.com
CONTACT: Steven J. Mento, Ph.D., President and CEO, +1-858-457-7222,, or Alfred P. Spada, Ph.D., Sr. VP R & D,+1-858-457-7223, , both of Conatus PharmaceuticalsInc. ***@**** ***@**** "
i was told if i treat with SOC then I cannot treat with the new protease inhibitor unless I relapse.
I can see from above post this is true
Charm
I can see from above post this is true
Charm
this was not the information that we had all expected. I find it a total mind blower.
I have an appt with My Doc who attended the meeting and I will se him Friday.
Trying to look on the positive side but not sure what that is anymore.
I was told I would be resistant because of SOC.....bummer bummer bummer
I need to vent I will get over it.
Im starting tx next week and need to go thru this with a positive mindset.
I have an appt with My Doc who attended the meeting and I will se him Friday.
Trying to look on the positive side but not sure what that is anymore.
I was told I would be resistant because of SOC.....bummer bummer bummer
I need to vent I will get over it.
Im starting tx next week and need to go thru this with a positive mindset.
Where have you been??? Haven't seen you around in awhile and good to hear that you're still alive!
Susan400
Susan400
The study you refer to - or at least the one I found - also seems to indicate that using the Riba/Peg combo for SVR patients without HCC is useful to reduce the chances of contracting HCC. Am I reading this right -- are they saying we should continue to treat with Interferon and Riba even AFTER we are SVR?? They throw in some things about the condition of the liver, age, length of time with disease and such but they seem to say that continued tx with Interferon and perhaps Riba reduces the chances of liver cancer fivefold. I dont know what to think about this whole article but thanks for the post. I was running out of things to worry about. LOL
Are you still blogging? Still writing? Havent seen you in a while. What is your status these days? You had some significant reduction of fibrosis last I heard. Any new discoveries?
Are you still blogging? Still writing? Havent seen you in a while. What is your status these days? You had some significant reduction of fibrosis last I heard. Any new discoveries?
Willows; are you certain that your doc said that you are Interferon restant? I too had a viral breakthrough on SOC tx at Week 32. At Week 12 I got a 3log+ drop and then began a slow VL decline until it rose at Week 32. If you got a 2log drop at Week 12 you responded to INF and ARE NOT a null responder which is what Susie is talking about. I'd talk to your doc very specifically about this.
Susie; I'm curious, was this data given in a formal presentation at AASDL or was it sidebar comments or perhaps meeting discussions by these docs. What I'm picking at is this may just be initial observations or speculation. There's no data anywhere on the topic.
Two AASDL presentations that I am anxiously awaiting the details are:
1.) November 5th @ 8:15 AM - PROVE2: Phase II Study of VX950 (TELAPREVIR) in Combination with Peginterferon ALFA2A With or Without Ribavirin in Subjects With Chronic Hepatitis C, First Interim Analysis C. Hezode; P. Ferenci; G. M. Dusheiko; S. Pol; T. Goeser; J. Bronowicki; S. Gharakhanian; D. Devonish; R. Kauffman; J. Alam; J. Pawlotsky; S. Zeuzem
This presentation gives interum data about the Arm C which is 12week VX950+INF+RBV followed by 12 weeks of SOC. This protocol is the same as Prove 3 Group D that I finished treatment for.
2.) November 6th @ 800 AM - Evaluation of Viral Variants During a Phase 2 Study (PROVE2) of Telaprevir with Peginterferon alfa-2A and Ribavirin in Treatment-naïve HCV Genotype 1-Infected Patients. T. Kieffer; Y. Zhou; E. Zhang; M. Marcial; R. Byrn; T. Pfeiffer; J. Miller; A. Tigges; D. Bartels; A. Kwong; P. Ferenci; G. Dusheiko; S. Zeuzem; J. Pawlotsky
I was excited to hear the Prove 1 and Prove 2 correlation between RVR and SVR. For VX950 tx RVR is defined as UND by Week 4. I started May 4th and became UND somewhere before May 18th. As Willy references, most Prove EVRs maintain their UND status throughout tx. After tx 91% of EVRs go on to be UND at post-tx Week 12. Of post-tx Week 12 UND, 100% are UND at 24 weeks after stopping tx, which is considered cured. For Prove 1&2, if a relapse occurs, it would within 4 weeks after successfully completing tx.
The numbers between Prove 1 and Prove 2 vary greatly. These may not be totally accurate but in Prove 1 like 2% of patients relapsed while in Prove 2 like 14% relapsed. Why the differnece between studies? Is it the cars that Europeans drive or the small portions of food they eat? :-)
Today I'm on pins and needles because soon (like yesterday) I'm to receive the results of my Week 26 (two weeks post tx) labs. It's in God's hands now and I hope he has good news.
One closing thought to Susie2007....any thoughts about future treatments with Albuferon, VX-950 and Ribivirin? It's not going on (yet) but that combo always seemed ike a powerful punch. I believe that many INF resitant people respond to Albuferon.
Mike
Susie; I'm curious, was this data given in a formal presentation at AASDL or was it sidebar comments or perhaps meeting discussions by these docs. What I'm picking at is this may just be initial observations or speculation. There's no data anywhere on the topic.
Two AASDL presentations that I am anxiously awaiting the details are:
1.) November 5th @ 8:15 AM - PROVE2: Phase II Study of VX950 (TELAPREVIR) in Combination with Peginterferon ALFA2A With or Without Ribavirin in Subjects With Chronic Hepatitis C, First Interim Analysis C. Hezode; P. Ferenci; G. M. Dusheiko; S. Pol; T. Goeser; J. Bronowicki; S. Gharakhanian; D. Devonish; R. Kauffman; J. Alam; J. Pawlotsky; S. Zeuzem
This presentation gives interum data about the Arm C which is 12week VX950+INF+RBV followed by 12 weeks of SOC. This protocol is the same as Prove 3 Group D that I finished treatment for.
2.) November 6th @ 800 AM - Evaluation of Viral Variants During a Phase 2 Study (PROVE2) of Telaprevir with Peginterferon alfa-2A and Ribavirin in Treatment-naïve HCV Genotype 1-Infected Patients. T. Kieffer; Y. Zhou; E. Zhang; M. Marcial; R. Byrn; T. Pfeiffer; J. Miller; A. Tigges; D. Bartels; A. Kwong; P. Ferenci; G. Dusheiko; S. Zeuzem; J. Pawlotsky
I was excited to hear the Prove 1 and Prove 2 correlation between RVR and SVR. For VX950 tx RVR is defined as UND by Week 4. I started May 4th and became UND somewhere before May 18th. As Willy references, most Prove EVRs maintain their UND status throughout tx. After tx 91% of EVRs go on to be UND at post-tx Week 12. Of post-tx Week 12 UND, 100% are UND at 24 weeks after stopping tx, which is considered cured. For Prove 1&2, if a relapse occurs, it would within 4 weeks after successfully completing tx.
The numbers between Prove 1 and Prove 2 vary greatly. These may not be totally accurate but in Prove 1 like 2% of patients relapsed while in Prove 2 like 14% relapsed. Why the differnece between studies? Is it the cars that Europeans drive or the small portions of food they eat? :-)
Today I'm on pins and needles because soon (like yesterday) I'm to receive the results of my Week 26 (two weeks post tx) labs. It's in God's hands now and I hope he has good news.
One closing thought to Susie2007....any thoughts about future treatments with Albuferon, VX-950 and Ribivirin? It's not going on (yet) but that combo always seemed ike a powerful punch. I believe that many INF resitant people respond to Albuferon.
Mike
So for alll the people who have relapsed after tx they will be able to tx with a P.I.?
Does that also apply for people that have had breakthru's during tx? will they too be able to tx with a P.I.?
To my understanding if you dont have a 2 log drop within 12 weeks you should stop tx and P.I.'s will not be offered
Just trying to absorb this.
t y
Does that also apply for people that have had breakthru's during tx? will they too be able to tx with a P.I.?
To my understanding if you dont have a 2 log drop within 12 weeks you should stop tx and P.I.'s will not be offered
Just trying to absorb this.
t y
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