Aa
Vertex study data
http://biz.yahoo.com/bw/071102/20071101006689.html?.v=1
I just don't see this as blockbuster data?
I suspect the discontinuation data will be a problem for the fda.
In PROVE 1, the overall discontinuation rate through 12 weeks was 18% across all telaprevir treatment arms and 3% in the control arm. This includes discontinuations due to adverse events, withdrawal of consent and patients lost to follow-up. The incidence of treatment discontinuations through week 12 due to adverse events was 13% and 2% in the telaprevir and control arms, respectively. The most common reason for discontinuation was rash, with 7% of patients discontinued for this reason in the telaprevir arms during the first 12 weeks of treatment. After week 12, discontinuations due to adverse events were 8% each in the telaprevir and control arms. Over the full course of the treatment period, the incidence of severe adverse events was 27% in the telaprevir arms and 24% in the control arm.
In PROVE 2, the overall discontinuation rate through 12 weeks was 14% across all telaprevir treatment arms and 6% in the control arm. This includes discontinuations due to adverse events, withdrawal of consent and patients lost to follow-up. The incidence of treatment discontinuations through week 12 due to adverse events were 10% and 3% in the telaprevir and control arms, respectively. As with PROVE 1, the most common reason for discontinuation was rash, with 7% of patients discontinued due to rash in the telaprevir arms, compared to less than one percent in the control arm during the first 12 weeks of treatment. Through to week 12, the time of the interim safety analysis being reported, the incidence of severe adverse events was 17% in the telaprevir arms and 10% in the control arm.
I just don't see this as blockbuster data?
I suspect the discontinuation data will be a problem for the fda.
In PROVE 1, the overall discontinuation rate through 12 weeks was 18% across all telaprevir treatment arms and 3% in the control arm. This includes discontinuations due to adverse events, withdrawal of consent and patients lost to follow-up. The incidence of treatment discontinuations through week 12 due to adverse events was 13% and 2% in the telaprevir and control arms, respectively. The most common reason for discontinuation was rash, with 7% of patients discontinued for this reason in the telaprevir arms during the first 12 weeks of treatment. After week 12, discontinuations due to adverse events were 8% each in the telaprevir and control arms. Over the full course of the treatment period, the incidence of severe adverse events was 27% in the telaprevir arms and 24% in the control arm.
In PROVE 2, the overall discontinuation rate through 12 weeks was 14% across all telaprevir treatment arms and 6% in the control arm. This includes discontinuations due to adverse events, withdrawal of consent and patients lost to follow-up. The incidence of treatment discontinuations through week 12 due to adverse events were 10% and 3% in the telaprevir and control arms, respectively. As with PROVE 1, the most common reason for discontinuation was rash, with 7% of patients discontinued due to rash in the telaprevir arms, compared to less than one percent in the control arm during the first 12 weeks of treatment. Through to week 12, the time of the interim safety analysis being reported, the incidence of severe adverse events was 17% in the telaprevir arms and 10% in the control arm.
So this stuff inhibits the stuff that breaks down the "scaffolding that maintains architecture"? Would this be considered anti-fibrotic? Wonder where the data on the 500? jm
something a bit different
"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. ***@**** ***@**** "
Drug stocks dip; Vertex slides on drug competition concerns
10:22a ET November 5, 2007 (MarketWatch)
BOSTON (MarketWatch) -- Drug stocks dipped in early action Monday, as shares of Vertex Pharmaceuticals tumbled over concerns about potential rivals to the company's hepatitis C drug candidate, telaprevir.
The Amex Pharmaceutical Index fell marginally to 344.47 and the Amex Biotechnology Index declined 1.3% to 816.31.
Shares of Vertex Pharmaceuticals lost ground for the second straight session in the wake of positive clinical study results for several hepatitis C drug candidates at a scientific meeting of liver specialists held in Boston late last week.
While Vertex released favorable data for its product, telaprevir, positive results were also reported for rival products being developed by Swiss drugmaker Roche and privately-held Romark Laboratories.
Vertex shares were down 14% at $24.93.
Also slipping were shares of Schering-Plough Corp. , down over 1% at $29.59. The drugmaker is developing a treatment for hepatitis C similar to telaprevir.
In other Schering-Plough news, partner Novacea Inc. said that it was halting Phase III clinical testing for the prostate cancer drug Asentar due to a higher than expected death rate amongst Asentar users. Novacea said that despite the setback, it and Schering-Plough plan to continue developing the compound.
Shares of Novacea plunged almost 70% to $2.26.
Yup, that's what is says alright. It also says 61% 12 week SVR with NO relaspes from prove 1 between post week 12 and 24. I guess that means 4% relaspe rate on prove 2. Andiamo, I'm not treating but am a little confused:) Some of the #s here don't seem to add up between the RVRs, EOT, and SVRs jerry
I have to confess, I have severe brain fog these days. That said, I read the numbers as 61% SVR for Telaprevir combined with SOC and 40% SVR with SOC only.
Hi, yes my quoting is correct: http://biz.yahoo.com/bw/071102/20071101006689.html?.v=1 and search vor n=79
This would probably mean a lower rate of ETR from Triple Therapy with telaprevir than from SOC. Or did I miss something?
regards, Drofi
This would probably mean a lower rate of ETR from Triple Therapy with telaprevir than from SOC. Or did I miss something?
regards, Drofi
I"n the 48-week telaprevir treatment arm (12+36; n=79) of PROVE 1, 65% had undetectable HCV RNA (<10 IU/mL) at end of treatment."
Hey, I've not seen these #s before. Are you sure you are quoting them correctly? Seems like SOC gets 80% eot und, then comes relaspe. jerry
Hey, I've not seen these #s before. Are you sure you are quoting them correctly? Seems like SOC gets 80% eot und, then comes relaspe. jerry
I felt the same way after I quit Telaprevir , after 6 days it was like I was clean of it and saw everything more clearly and energetically. I could listen to people talk and not fall apart inside my head.
I certainly felt a general malaise that I could not describe easily that disappeared once I stopped Telaprevir and continued with SOC drugs. I don't know how much that increased the dropout rate.
Anyone else in Prove 3 experience this?
Anyone else in Prove 3 experience this?
"I thought that 91% SVR for RVR was true for soc too? I'm new to tx, so i'm just trying to wrap my mind around all these numbers and statistics"
You are correct, but that is for 48 weeks of SOC. This is for 24 weeks. And lots more people get RVR on the new drug.
My understanding is that it is possible to stop SOC at 24 weeks now with similar, almost 90% SVR. I hope this drug helps more people succeed though, and that the side effects are tolerable, given it seems to be another poision in the mix (as any new drug will be).
You are correct, but that is for 48 weeks of SOC. This is for 24 weeks. And lots more people get RVR on the new drug.
My understanding is that it is possible to stop SOC at 24 weeks now with similar, almost 90% SVR. I hope this drug helps more people succeed though, and that the side effects are tolerable, given it seems to be another poision in the mix (as any new drug will be).
I"n the 48-week telaprevir treatment arm (12+36; n=79) of PROVE 1, 65% had undetectable HCV RNA (<10 IU/mL) at end of treatment."
Does someone know new data how many get ETR after 48 weeks of SOC?
Regards, drofi
Does someone know new data how many get ETR after 48 weeks of SOC?
Regards, drofi
"I thought that 91% SVR for RVR was true for soc too? I'm new to tx, so i'm just trying to wrap my mind around all these numbers and statistics"
You are correct, but that is for 48 weeks of SOC. This is for 24 weeks. And lots more people get RVR on the new drug.
You are correct, but that is for 48 weeks of SOC. This is for 24 weeks. And lots more people get RVR on the new drug.
I thought that 91% SVR for RVR was true for soc too? I'm new to tx, so i'm just trying to wrap my mind around all these numbers and statistics.
From a late edition of the news today from Reuters -
"We wait for competitors to provide meaningful clinical data that would trump Vertex," said Richard Smith, an analyst at JP Morgan, which has or recently had a banking relationship with Vertex. "We remain positive on the prospects for telaprevir and while the road is likely to be rocky for the stock, we thing long term investors will be rewarded."
Earlier editions had quotes from a number of investment houses that have less of a reputation than JP Morgan.
"We wait for competitors to provide meaningful clinical data that would trump Vertex," said Richard Smith, an analyst at JP Morgan, which has or recently had a banking relationship with Vertex. "We remain positive on the prospects for telaprevir and while the road is likely to be rocky for the stock, we thing long term investors will be rewarded."
Earlier editions had quotes from a number of investment houses that have less of a reputation than JP Morgan.
I am a patient of one of the top Hepatologists. I am relaying his thoughts that RVR is RVR no matter what. His advice to me was that I am safer in the 48 week arm because of my age, not because of previous failures.
The CEO of Vertex last week gave the 91% SVR for RVR people.
I certainly agree that we will not know for sure until the Prove 3 results are in and that will not be for a while. The older debates were not just about RVR meanings for treatment experienced people, they were about the meaning of RVR when a PI is used. That has been put to bed with Prove 1 results.
The CEO of Vertex last week gave the 91% SVR for RVR people.
I certainly agree that we will not know for sure until the Prove 3 results are in and that will not be for a while. The older debates were not just about RVR meanings for treatment experienced people, they were about the meaning of RVR when a PI is used. That has been put to bed with Prove 1 results.
Willow, I am right there with you with the irrational exhrberance.
I know so little.
But I do know the virus has a nasty habit of creeping back and UND means undetectable and does not mean cleared. I was on the B arm of the study ( or at least I think so) and frankly despite all the crappy Sx I would not have it any other way. Don't know how others went through 2 more than Tx's w/o success. I barely survived the first and amd inching my way through the second and that is with the presunmed RVR..
I know so little.
But I do know the virus has a nasty habit of creeping back and UND means undetectable and does not mean cleared. I was on the B arm of the study ( or at least I think so) and frankly despite all the crappy Sx I would not have it any other way. Don't know how others went through 2 more than Tx's w/o success. I barely survived the first and amd inching my way through the second and that is with the presunmed RVR..
RVR is linked to SVR for Prove 1 and Prove 2 (see my post above) which is treatment naive patients.
My question to Andiamo1 was why he thought the same for non-responders....that is still an open question yet to be detemined for us Prove 3 trial participants.
I'm one of the first here to complete Prove 3 tx because I was in Arm D (12 weeks VX950+RBV+INF followed by 12 weeks SOC). My Week 26 labs were drawn last week and I'm anxious to hear that my PCR two weeks post tx is still UND.
My question to Andiamo1 was why he thought the same for non-responders....that is still an open question yet to be detemined for us Prove 3 trial participants.
I'm one of the first here to complete Prove 3 tx because I was in Arm D (12 weeks VX950+RBV+INF followed by 12 weeks SOC). My Week 26 labs were drawn last week and I'm anxious to hear that my PCR two weeks post tx is still UND.
Laid out on the couch listening to cnbc and just heard the head of vertex's interview.
Interesting.
65% success rate and shorter TX time according to him (....)
He's wondering why the stock is off 10%.
wyntre
Interesting.
65% success rate and shorter TX time according to him (....)
He's wondering why the stock is off 10%.
wyntre
We may be getting ahead of ourselves, I can't help it. I really need to tx again and would like to only do 24 weeks of tx.
But the question of RVR and SVR has been linked for a while now, I think it is a fine point you make, because it HAS not been sorted out between non-responders and tx naive folks. But I feel pretty confident that the correlation can be used for any patient with the virus, if you reach RVR, there is a better chance you will maintain SVR. I think the numbers will be different, but no one has compiled exact numbers yet. Just my irrational exhrberance. And great need.
Willow
But the question of RVR and SVR has been linked for a while now, I think it is a fine point you make, because it HAS not been sorted out between non-responders and tx naive folks. But I feel pretty confident that the correlation can be used for any patient with the virus, if you reach RVR, there is a better chance you will maintain SVR. I think the numbers will be different, but no one has compiled exact numbers yet. Just my irrational exhrberance. And great need.
Willow
Where is RVR linked to SVR for non respponders? Are we getting ahead of ourselves here?
From the boatload of info I have read this morning, with the 91% success rate for folks with RVR and then SVR, the research community has finally concluded that the two are linked. Now the stock is down because the investment community wanted to see about 70%, but we don't care, the investment community is feeling a bit lemming like these days, what with the market wobbling like it is.
Two things I read that made my day here in "stage 3, non-responder" land...."telaprevir is definitely marketable" and "60 to 65% with 24 weeks of tx". I'm rocking and rolling about this and as Andiamo says...the numbers should be pretty comparable with non-responders. So when Doc Scott says to me....Jackie, let's try again...24 weeks with 60% of a chance..I'm gonna jump on it.
The stock will rebound, this up and down stuff has gotten kind of repetitive with biotech, especially Vertex. In the grand scheme of things, not sure how important the daily price of Vertex is...just the numbers they are gathering for the FDA. Today is a good day for numbers, I think.
Willow
Two things I read that made my day here in "stage 3, non-responder" land...."telaprevir is definitely marketable" and "60 to 65% with 24 weeks of tx". I'm rocking and rolling about this and as Andiamo says...the numbers should be pretty comparable with non-responders. So when Doc Scott says to me....Jackie, let's try again...24 weeks with 60% of a chance..I'm gonna jump on it.
The stock will rebound, this up and down stuff has gotten kind of repetitive with biotech, especially Vertex. In the grand scheme of things, not sure how important the daily price of Vertex is...just the numbers they are gathering for the FDA. Today is a good day for numbers, I think.
Willow
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