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.

[miked]

This board recently debated the correlation between RVR and SVR for the VX950 studies.  The paragraph about RVR was of particular interest to me....


RVR:
In PROVE 1 and PROVE 2 combined, on an ITT basis, 77% of patients receiving telaprevir in combination with peg-IFN and RBV achieved a rapid viral response at 4 weeks (79% in PROVE 1, 75% in PROVE 2), defined as undetectable HCV RNA <10 IU/mL as measured by the Roche TaqMan® assay, compared to an average of 12% of patients across the control arms of PROVE 1 and PROVE 2 (11% in PROVE 1, 13% in PROVE 2; p<0.001 for the comparison in each study).

For those patients that achieved RVR, completed 24 weeks of telaprevir-based therapy, and had data available for SVR analysis, 91% achieved an SVR 24 or SVR 12. This finding demonstrates a correlation between RVR and SVR in a 24-week telaprevir-based treatment regimen.

Mike

[copyman]

i would much rather have the odds of getting the rash then the odds acheiving SVR with the present drugs, 10% chance of getting rash with a 91% chance of SVR with RVR vs 40% chance of SVR with present combo drugs. no brainer

[3txsofar]

Perhaps we have expected too much and thus some are disappointed.  But I see a drug that allows treatment in half the time - 24 weeks oppossed to 48 - and improves SVR by at least 50% as a blockbuster.

[Andiamo1]

I agree and I don't see any way the FDA will disallow a drug that can save so many more lives than the current SOC.

Remember, these trials do not allow rescue drugs and once they are allowed I think the dropout rate will be close to the same as SOC with some additional due to the rash.

[Upbeat]

First studies demonstrating greater than 60% sustained viral response with half the standard treatment duration in genotype 1 chronic hepatitis C patients Co announces results from interim analyses of PROVE 1 and PROVE 2, two Phase 2b clinical trials evaluating the investigational hepatitis C protease inhibitor telaprevir, dosed in combination with pegylated interferon and ribavirin. In 24-week telaprevir-based treatment regimens, genotype 1 treatment-naive HCV patients achieved sustained viral response rates of 61% and 65% in PROVE 1 (SVR 12 and SVR 24) and PROVE 2 (SVR 12), respectively. In addition, clinical researchers reported a correlation between achieving rapid viral response and achieving SVR in a 24-week telaprevir-based regimen. Interim analyses of telaprevir safety from PROVE 1 and PROVE 2 appear consistent with prior analyses, with the most common adverse events, regardless of treatment assignment, being fatigue, rash, headache and nausea.

[Andiamo1]

The non responder/relapser study is the one that I am in and is ongoing.  There is no data on SVR, since no one has been in the study long enough.  Judging by the RVR results, the numbers should be about the same as the naive study.

Meanwhile, Vertex stock is off by more than 20% today.  Partly due to the Alinia study.

[3txsofar]

The horse's mouth - the Vertex CEO - will be on CNBC at 10:40 EST.  

[Andiamo1]

According to the CEO, the 60% SVR rate includes an 18% dropout.

Now I am really puzzled about why they don't allow rescue drugs.

[Proactive]

I understand what everyone is saying. While the fda may have volumes of bylaws regarding trials, drug approval etc., it really comes down to a simple formula (imo) do the benefits of the drug outweigh the risk to the patient. It appears it certainly does in certain subgroups(I also thought there was talk of shortening soc in these same subgroups?), I think the jury is still out on others,-again
(do benefits outweigh risk),,,In light of the new fda warnings on labeling of some of our "rescue drugs", does the fda want to risk possibly more patients to some of these drugs very drugs they added labeling to? As the devils advocate in me come out, I have to take myself out of the patient's shoes and attempt to place my feet in the shoes of otheres..Also keep in mind that rescue drugs aren't a part of soc, lower dosing and discountinuation is, even though many of us get them.
Back to painting, thought I'd feel a bit better if I got out, we'll see how long it last (g)

[miked]

Eric,

What's your thoughts about "Judging by the RVR results, the numbers should be about the same as the naive study."?

I was very glad to hear that they are linking RVR to SVR.

Mike

[Proactive]

I really think the side issue is the biggy, and may be overcome, but it could take awhile to do it..
I've said enough on the subject, although don't some of these drugs get approved on some kind of continued investigational status?
I'm out, later

[Andiamo1]

The dropout rate will improve once rescue drugs are given.

The SVR rate for RVR people is 91%  

[willows]

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

[glucklich]

Where is RVR linked to SVR for non respponders? Are we getting ahead of ourselves here?

[willows]

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

[wyntre9]

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

[miked]

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.

[glucklich]

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..

[Andiamo1]

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.

[3txsofar]

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.

[jamimapuddle]

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.

[Sincebirth]

"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.

[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."

Does someone know new data how many get ETR after 48 weeks of SOC?

Regards, drofi

[moahunter]

"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).

[moahunter]

If RVR SOC.

[Andiamo1]

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?

[glucklich]

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.

[orleans]

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

[drofi]

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

[Andiamo1]

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.

[orleans]

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

[Andiamo1]

Here is a link to a nice comparison done by 3txsofar

http://www.medhelp.org/posts/show/340173

[mikesimon]

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.

[Proactive]

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, [phone],, or Alfred P. Spada, Ph.D., Sr. VP R & D,[phone], , both of Conatus PharmaceuticalsInc. ***@**** ***@**** "

[orleans]

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