Vertex Telaprevir EASL info: 68%

Yippee!

From an Australian paper:

RADICALLY improved treatments for one of the world's worst health scourges are looking more likely after scientists reported patients were cured more quickly and more often if an experimental new drug was added to the normal therapy.

http://tinyurl.com/6ctjkq

Excerpt from a financial article at the Motley Fool:

Yesterday, at the European Association for the Study of the Liver (EASL) conference, Vertex reported heartening new clinical trial data for its lead drug, telaprevir.

Vertex dispelled any ambiguity about the PROVE-2 results. Its new efficacy data showed that 68% of telaprevir-treated patients were ultimately cured of hepatitis C, compared to only 48% of patients in the control group. Obviously, that's a far more promising outcome, and it matches PROVE-1's 20-percentage-point improvement on current treatments' cure rates.

http://tinyurl.com/6xc2ry

And I bet the late breaker news on boceprevir and others will be good as well. The 2011 is a bummer to read...I am barreling down the road toward treatment, but if I fail at least there is hope for a Plan B now.

[Marcia2202]

That's great news... I wish they would announce when it is finally going to be on the market. ????? It's like having someone dangle a delicious piece of chocolate cake in front of your mouth.... but you can't reach it.

Marcia

[HectorSF]

"Neil Graham, the Adelaide-trained doctor who is leading the hepatitis C program for telaprevir's maker, Boston-based drug company Vertex, said that if subsequent trials went well, an application to register the drug could be lodged with US regulators in 2011.

Hector

[fretboard]

The 68% is very good news and goes along with what the nurse at UCD told me about how things have been going with their study trials.  She told me when I went there to join a trial that their overall percentage rate was close to 70% with the persons who completed and reached SVR.  I'm barrelling down the road to that "whiter shade of pale", as well.  I was told that I would receive the consent form around mid- May.  Here's to hoping that all goes well and we all have minimum sx.  God Bless  

[drofi]

no, 68% is not good. The patients were native to therapy, no relapsers or nonresponders. Handselected patients. In addition, the 32%  who failed SVR might have resistent clones now against the complete class of proteaseinhibitors and have lost this option for ever, even when there are second generation PIs available.
If one has enough time, it might be better to wait for quadrupel therapy (eg with Telaprevir and R1626) to avoid resistent clones.

drofi

[Marcia2202]

Thank you for the information. :-)

Marcia

[jmjm530]

Drofi: no, 68% is not good. The patients were native to therapy, no relapsers or nonresponders.
---------------------------------
The study compared treatment naive to treatment naive. 68% SVR compared to 48% SVR but perhaps more important IN HALF THE TIME. 24 weeks for Telaprevir as compared to 48 weeks of SOC. That's half the exposure to interferon. What's more, the Telaprevir group had an 18% drop out rate compared to 4% SOC. That could be read two ways -- but one way is that the 68% SVR figure could be a lot higher if they are able to come up with effecive solutions to combat the rash and/or shorten Telaprevir exposure in the future to perhaps even eliminate the rash. I'd say these results are "radically improved" over SOC, using the words of the Australian paper. As to the potential of losing the option to treat with PIs forever, I haven't seen anything published to suggest that this risk outweighs the benefits.

I agree that anyone who can afford to wait for potentially even better treatments -- perhaps one day without interferon -- should. However, if I made a decision to treat -- either because of advanced stage or other reasons -- personally I would not hesitate to choose PI triple therapy over SOC.

-- Jim

[foofighter]

Come on, it is good news. Even better news depending on who you are. The head doc at our transplant center here, looked me in the eye and said "You realize you have a less than 10% chance of responding to treatment."

And of course I won't have a 68% chance with telaprevir either...but better than without! And check out the what Toughluck reports for his trial. Rescue drugs, dermatological help and more. So maybe that dropout rate will plummet and it will be even higher.

I am trying hard to stay hopeful. It is good news.

[Marcia2202]

I'm sorry to hear that the doc believes you have such a small chance... I pray that you are in the 10% and not in the 90 ... Or else that you can get your hands on telaprevir as soon as possible.  God bless. Marcia

[SteveHepC]

Jim:
My enzymes are normal, but my Viral Load is over 2 million. I responded then relapsed, I'm 2B. The treatment was very hard on me.......sides were terrible. My Gastro is a good one, and he thinks that because I'm 68, with no symptoms......it makes sense to wait. In the meantime, I take about 12 supplements.....including DGL, NAC, Alpha Lipoic Acid, L-Glutamine, Milk Thistle, Super Omega-3, Multi Vitamin with lots of 'D', Vitamin C, LIV 52, CoQ-10, and Mushroom Extract. I also excersize and drink mucho filtered water. If anyone knows about supplements, please speak up.
Thanks,   Steve

[jmjm530]

Not sure what you mean by "symptons" , but certainly on top of the list is how much liver damage you have determined by biopsy. If you have signficant liver damage, then you should consider treatment regardless of symptons. If you don't have significant liver damage, you have the option to wait. Normal enzymes and viral load don't necessarily correlate with liver damage. How recent was your biopsy that hopefully you've had and what stage did they say you were? If you haven't had a biopsy, I'd say that would be the next step in terms of making any treatment decisions.

-- Jim

[SteveHepC]

Biopsy not an option.........St Jude Mechanical Heart Valve requires that I take mega doses of Coumadin. Doctors won't do a biopsy........too dangerous. I bleed massively just from a pricked finger. MRI's and CT Scans show no Liver abnormalities/enlargement. No ascities, no spleen enlargement. None of the markers like Total Protein, Albumin, LDH, Platelets indicate damage. 'Symptons"! Very funny. I mean, of course, no dark urine, no fatigue, no jaundice, no loss of apetite, no wierd colored stool.
Thanks for your response.

Steve

[Marcia2202]

How accurate are MRI and CT scans to determine fibrosis/cirrhosis?

Marcia

[SteveHepC]

Google CT Scan, Cirrhotic liver. They show pictures and compare it to normal....The difference is amazing. However, they cannot determine stage of fibrosis. I'm trying to get up the money to fly to California for a Fibroscan.

Steve

[Marcia2202]

I thought so, that they cannot determine fibrosis. I'm sorry to hear that you cannot do the biopsy and hope you'll be able to do the fibroscan soon.  It really strikes me each time, that a super power like the USA doesn't have free medical care... Well, lets not get into politics.....

Someone suggested I see some videos, when I first joined the forum. There is a very interesting one called 'Why You Should Treat Your Hep C now!'  on www.hcvsupport.org

To find it you scroll about half way down the page to the left under 'Resource Directory' there is something called 'Videos Presentation'. It's the third.

I found it very informative...

Marcia

[drofi]

Quote: “As to the potential of losing the option to treat with PIs forever, I haven't seen anything published to suggest that this risk outweighs the benefits.”

Have a look to this paper, perhaops you did not notice it.
“The emerging field of HCV drug resistance”
http://tinyurl.com/yocrjc
I have the fulltext, it is a great paper. The truth sometimes hurts.

In addition to the published data cited in the paper: The first Boceprevir study resultet in 15% SVR for tripple therapy in former nonresponders. The other 85% developed resistancies against Boceprevir.
The PI and PolI are a great chance in future, but as known from HAART for HIV, resistance is a huge problem and should be avoided by combination of different classes.

regards, drofi

[scaredwife]

My husband was on the boceprevir trial for 48 weeks and relapsed. He's 1b and was UND somewhere between 20 and 24 weeks. He was treatment naive. Does this mean that he developed clones that are resistant to PIs?

[jmjm530]

This is from your link. Perhaps there's something more specific to treatment in the subscribed version. It's a very general statement that I assume the research professional Hep C community is well aware of as this topic comes up often, but apparently not everyone sees it as "huge problem" and sees Telaprevir as "no good".
That includes my doc who runs multiple trials, including Telaprevir, as well as others who have posted here. That said, it doesn't mean some degree of risk potentially exists, but my take so far is that PI's appear to be a better alternative than SOC for those who decide to treat. Anecdotally, I have first hand experience of what 54 weeks of interferon can do to your body and life. Things would have been a *whole* lot different for me had I only treated 24 weeks.
----------
Background: With 170 million people infected worldwide and an inadequate current standard of care, hepatitis C virus (HCV) infection represents a major unmet medical need. Multiple companies are working on the discovery and development of specific HCV antiviral drugs, including inhibitors of HCV polymerase, protease and NS5A. Because of the error-prone nature of viral RNA replication, resistance mutants will develop that could present a potentially significant challenge to developing antiviral treatment regimens. Objective: Here, we review the major drug classes currently in preclinical and clinical development and the resistance mutations specific for each class that have been identified from cell culture and/or in vivo studies. Methods: We have analyzed currently available scientific literature to create a comprehensive review of the current state of the art in the field of HCV resistance to specific antiviral agents, in vitro and in vivo. Results/conclusion: Most specific HCV inhibitors described in the literature can select resistant viral variants in cell culture and in the clinic. Interplay of a mutant's fitness and its level of resistance will determine its clinical importance. Combinations of non-cross-resistant classes of dugs will be key to successful antiviral therapy. The number of drugs in a combination as well as the optimal duration of antiviral treatment, are important issues that need to be addressed in future studies.

[Trish77]

Steve,

If your next step is a Fibroscan, do you have information on why that is superior to a CT Scan?  How much does a Fibroscan determine fibrosis?  Does any insurance cover this if it's your only option?

I can, and will, read up on it but I confess it's not my immediate priority.  It IS, however, of great interest to me....you are right in the middle of exploring this so I'm asking your take on it.  Thank you and good luck to you.

Trish

[foofighter]

Two different animals. Fibroscan is specifically made to diagnose liver fibrosis. Which is good, because now and again you may have a questionable result even with biopsy.

http://www.echosens.com/en/ex1.html

From what I understand, CT will show advanced liver disease by revealing a bumpy, nodular surface but have difficulty representing what is going on inside the liver fibrosis-wise when it is at a lower stage.

My Fibroscan results matched my CT. Not always are you able to get perfect scan results, but I was fortunate to have the best Fibroscan Operator out there : )

There is lots of info on these boards discussing this exact topic.

[foofighter]

Der. I see you already have jumped into one of those discussions with Mike and have at least the knowledge I just posted.

The scan I had was out of pocket and I traveled to Los Angeles. I was put in touch with HR though Forseegood and I know that there are at least a few other people that have made the trip as well. I think

Other peeps here know of other docs who have machines, that possibly are covered by insurance.

Steve, willl you be seeing HR for your scan when the time comes?

[Trish77]

Foo:  Der. I see you already have jumped into one of those discussions with Mike and have at least the knowledge I just posted.
--------------------------------------------------------------------------------------------------------
No, actually I didn't have the information you posted.  If you posted that link during that discussion, I missed it. I did read up on other things but nothing that gave me the sort of definitive data I was after.  The link you posted today gets me a little closer after reading  a study linked from that page. It states:

CONCLUSIONS: FibroTest and FibroScan have excellent utility for the identification of HCV-related cirrhosis, but lesser accuracy for earlier stages. Refinements are necessary before these tests can replace liver biopsy.

That gets me closer to the kind of information I'm after, which is when would each of CT Scan, Fibroscan/FibroTest or biopsy be appropriate.  I'll keep reading as I have time.  Thanks.

Trish

[Trish77]

Steve, in your case I can see why a Fibroscan is what you're after when a biopsy is out of the question.  I wish you good luck in getting the necessary requirements in order.

Trish

[Andiamo1]

It seems that you have not watched the latest Vertex presentation just released on their website.  They have specific numbers for RVR from the Prove 3 trials.

You also state that trial participants are hand picked.  That is not true.  I am stage 3, failed 7 previous treatments and I was 67 years old; they picked me!  I think anyone hand picking for positive outcome would run from me :).

If you fail to achieve SVR when you use a protease inhibitor you will likely have more resistant strains to the protease inhibitor you used and any other SIMILAR protease inhibitor.  You will not have a general resistance to all protease inhibitors.  Perhaps all that target NS3,  but definitely not all PIs.  In addition, within 6 months most of those strains will revert to wild type virus, so Telaprevir will still help eliminate the wild virus and you will need something that targets other than NS3 along with it.

[geterdone]

These three links will give you a better understanding of the vx-950 trials along with the just released presentation at the EASL.

Jasper

Chart showing the Prove trial phases.
http://www.vpharm.com/current-projects/drug-candidates/telaprevir-VX-950.html

News release about the EASL.
http://investors.vrtx.com/releasedetail.cfm?ReleaseID=306390

EASL presentation.
http://investors.vrtx.com/events.cfm

[kespr]

Just listened to the web cast from vertex from April 24 from EASL and the numbers from the late breaker news on the 107 study(Phase 1 & Phase 2 null responders and relapsers from control groups) look great. Even though they don't have SVR numbers there is great hope for null responders

[drofi]

There is a difference between RVR and SVR, please don't forget this. The press release of companies does not impress me very much anymore. Vertex has told us much better numbers all the years before, but always selling evrything as a great success. Yes, for vertex the glass is halffull, but for the relapsers from there studies it is half empty.

Andiamo, obviously you did not read the cited review about resistance, only the abstract. Read this:
"The fraction of  this mutant decreased in the follow-up period but it was still
present after 3 – 7 months. Variants with the mutations at
residue 155 represented the most fit resistant species. After
the end of treatment, and through the follow-up period,
their fraction in the population was only modestly reduced.
The R155 mutants confer about 10-fold resistance to
VX-950 and other protease inhibitors. A study with a Merck
protease inhibitor in a chimpanzee also found that the
R155K mutant was detectable in the virus population for
more than 8 months after the end of treatment [60] ."

There are many more facts described in the review, but please read it before you argue against it.
We have to thank all the guineapigs running through these studies and being heroes for comming generations of patients.

[Bigfloyd]

Not to be overly negative, but a couple points for the Vertex hopeful:
1) The stock market remains skeptical and VRTX continues to just tread water after declining significantly over the past 6 mos.. The stock took another hit after last week's announcements.
2) The PI's are considered to be at least 3 years out (which has been the case for years now).

If you are waiting to treat based on the imminent release of these and other new drugs, you might want to think again!  The reality is that the PI's are not a cure as originally hoped for, they have SX's that are worrisome, and now are focused only on increasing efficacy of Peg/Inf and Riba while shortening treatment.

[Andiamo1]

drofi: You did not read my comment.  I said that "In addition, within 6 months most of those strains will revert to wild type virus"  the key word there is "most."

Also, the studies showed a direct correlation between RVR and SVR.

There could be many long term effects of all the drugs we take.  There clearly are for SOC and there probably will be some for PIs as well.  Telaprevir is a very different drug than BILN and it was put through all the animal studies that BILN was subject to.

There are many ways to interpret data.  The glass can be half full or half empty - your choice.

It would be nice to take a single pill and have a  100% chance of being cured.  Telaprevir is not that, but it is a substantial improvement over SOC and there are studies to show that. What SXs are worrisome?  Are they more worrisome than SOC SX?  So far, nothing I have read comes close to the permanent SX of SOC.  If you know of some, please post them instead of calling them "worrisome".

I am no expert on this and I think this discussion is healthy if we can all learn something by it.

Since when does the stock market care one whit about the efficacy of a drug or whether it poisons someone.  The price is driven by traders in hedge funds that are looking to get in and out and  make a few bucks.  The rest of it is driven by analysts that have some knowledge of the drugs, but are not experts.

I bought it at 16, sold half at 26 and still have the rest.  All that in one month!  Not too shabby a performance.

[Bigfloyd]

"Since when does the stock market care one whit about the efficacy"

Vertex says their company is built on Telaprevir. The current consensus is that Vertex has a lead over the competition, but that that lead is likely to be short lived. Efficacy is what drives FDA decisions. Many analysts are qualified experts. Their job is to discern the facts from the bs.

"If you know of some, please post them instead of calling them "worrisome"." Sorry about that. I thought Telaprevir sides were well known on this board. Certainly they have been addressed in many of the press releases from Vertex and elsewhere. The primary concern is rash. This is not the Riba rash that many have experienced. It's a show stopper rash. One of my docs described it as Stevens-Johnsen rash and that he heard 1 person had died of it.

I have followed Vertex for the last year and half. In that time, Vertex moved from saying to expect approval in 2009 and now say 2011. And what they are really saying now is that they hope to start the registration process in 2011. Don't hold your breath.

For you, it is all probably moot since you are already in a trial. For the rest of us, I am concerned that some will read the optimism as meaning there is real treatment improvement right around the corner.

Nice move on the stock trade btw.

[Andiamo1]

I think that Telaprevir is such a substantial improvement over SOC that it will be approved before 2011. Vertex is filing for approval for treatment failures bypassing phase 3 trials.  |They are using data from Prove 3.  If you listened to the latest presentation on the website, you will see some impressive numbers for relapsers, non - responders and null responders.

The phase three trial will have rescue drugs and a dermatologist to treat the rash, so the numbers will improve substantially again, since here will be fewer dropouts.

This is an emotional topic for me, so sorry if I appear antagonistic.  Those of us that are stage 3 have no time to wait and this drug appears to have a good chance of treating many of the people that had no chance with SOC.

Right now, the latest data suggests 60 -68 percent SVR rates.  That will improve when the move to twice daily dosing and provide rescue drugs and help with the rash.

[geterdone]

Why do you feel that dosing twice a day is better than 3x in a 24 hour period?

Thanks!
jasper

[hippygem]

It says 2010.

RADICALLY improved treatments for one of the world's worst health scourges are looking more likely after scientists reported patients were cured more quickly and more often if an experimental new drug was added to the normal therapy.

More than 180 million people worldwide, including 250,000 in Australia, are infected with the hepatitis C virus, which, if untreated, can lead to liver cirrhosis and cancer. Currently the only treatment is a 48-week course of two drugs, pegylated (or slow-release) interferon and ribavirin, which are notorious for causing a "brain fog" that makes it hard for people to stay at work.

Results from two studies presented to a European conference of liver specialists show that when a new drug called telaprevir was taken alongside the usual drugs for the first 12 weeks of treatment, the success rate increased from 41per cent of treated patients to 61per cent. More significantly, the treatment time for those given telaprevir was halved from 48weeks to 24 weeks.

In a separate but related study due to be presented last night, the success rate for patients given telaprevir rose to 68per cent.

Telaprevir is the most advanced of a new class of drugs for hepatitisC infection called protease inhibitors, which work by blocking a key stage of the virus's replication cycle.

Presenting the findings at the conference of the European Association for the Study of the Liver in Milan, John McHutchison, the Melbourne-trained lead investigator and professor of medicine at Duke University in the US, said that if these results were borne out in a larger trial about to start, the drug had the "potential to halve treatment duration in most subjects".

"This is a very big step forward," Professor McHutchison told The Weekend Australian. "If this goes well in phase III trials (about to start), we will be able to decrease the duration of therapy from a year to six months. This is a huge advance - but we have still got our hurdles."

Professor McHutchison said side effects from telaprevir were an issue and included an itchy rash and anaemia. As a result, more patients dropped out of telaprevir-based treatment (18 per cent) compared with normal therapy (4 per cent).

Australian experts at the conference welcomed the results as "absolutely exciting". Greg Dore, head of the viral hepatitis clinical research program at the Sydney-based National Centre in HIV Epidemiology and Clinical Research, said that although there was some additional toxicity from telaprevir, its ability to halve treatment time would be a huge benefit.

Neil Graham, the Adelaide-trained doctor who is leading the hepatitis C program for telaprevir's maker, Boston-based drug company Vertex, said that if subsequent trials went well, an application to register the drug could be lodged with US regulators in 2010.

[Andiamo1]

The three doses have to be 8 hours apart. In my case that meant 8am 4pm and midnight.  You are supposed to take it with 300 calories of food and eating that much at midnight was a pain for me.

I did discover Dove Unconditional Chocolate and that sure improved things -- LOL.

Eric

[moahunter]

While these results appear hopefull on the surface, I also think people have to be a bit careful in assuming that this represents a better treatment just around the corner. For some people who have failed SOC, then yes, this could be the answer. But as to whether it is worthwhile to add another drug to the mix, that also has side effects (some of which we may not yet know), in the hope that will enable a shorter treatment period, I think the jury still remains out as to whether it is worth it. For some people, it may not be. The protocol may end up, try SOC first, see if you are RVR, and if not, restart a month later with this new treatment. The ideal protocol will probably take years to work out, just as it has with SOC.

Lets face it, people are struggling on our boards with SOC as it is. I'm not yet convinced that adding another drug, which results in a slightly higher response rate but more sides, is going to be as meaningful as some expect. Yes, it will help some. But, my fear, is that things like the "rash" may just scare more people away from treatment.

[Willy50]

I've been waiting to read about the fallout from EASL.  It appears that the news stories are beginning to trickle out about comparing Telaprevir to Boceprevir.  The consensus seems to be that Vertex is still in the lead.  In my opinion they are significantly so.

They seem to have the strongest proven efficacy.
To date with lots of data they have proven that they can effectively halve the treatment time WHILE increasing the SVR about half again over SOC.
They are on track to be first to market.

They may actually have a shot at using the Prove 3 treatment failures trial as a registration trial.  That means that when the results of Prove 3 are all in (In only about a month) they can submit the data to the FDA and say; this is the only treatment that exists for prior treatment failures that improves response rates significantly better than SOC.  The FDA could decide to rapidly approve the drug combo for treatment failures.  It is conceivable that the drug could be approved (and only for past TX failures) fairly soon.  The retreatment SVR rate for past SOC failures is generally thought to be in the single digits.  Vertex could bring this much much higher and likely in a shorter period of time.

Yes, it's true that triple therapy may not be without it's dangers.  SOC is dangerous enough as it is; read the black label warnings on the treatment that come with the drugs.  Read the boards; there are threads about many TX related post treatment side effects; auto-immune disorders, IBS, CFS, dental issues, metabolic issues, depression, persistent pain which follows TX.  I am not trying to be critical of SOC but I am saying that it is not without it's inherent problems.  I am excited that a drug compound is soon to be available which could at the minimum halve our exposure to interferon and ribaviren.  The new Phase 3 trial will have one arm in which the participants have only 8 weeks of triple therapy followed by 16 weeks of SOC.  

IF there is little difference between response rates between the "8 & 16" compared to the "12 &12" then one could conclude that an even shorter course of triple therapy could be needed.  One might not even need to treat for 24 weeks.  The results of this trial won't be out for quite some time but I would venture a guess that some phase 3 trial participants will be posting here and you could get a preview WELL before the trial concludes.  Obviously, a shorter triple therapy course of treatment should be safer, have fewer rash issues while still netting a shorter SOC couse of treatment.  

I believe that triple therapy may prove to be safer and healthier than some of the enduro treatments we are now faced with.  The new results are showing that ever so called "null responders" do indeed respond with tremendous rapid viral load reductions.  A question that remains is if the viral load can be rapidly brought down whether standard SOC can take them the rest of the way home.

By the Fall liver conference (AASLD) I think there may be answers to a few of these questions.

Best,
Willy

[Andiamo1]

Right on!!

[moahunter]

Agreed - if SOC can significantly be shortened, tripple therapy may make sense. Any new treatment option is good, and it is exciting that new drugs are coming.

But, as at the moment, people will be left in a position of balancing whether the risks of chemicals outweigh the benefits. The extent to which new drugs tip that balance will be entirely individual, and will be a combination of factors, including success rate, cost and availability (we don't yet know to what extent insurance will or will not cover new therapy's, and not everyone is insured), side effects (both perceived and real), and the hazard that a failed attempt with a new treatment may result in resistance to better treatments in the futurer.

I will be really excited when we get a replacement for Riba, or interferon, or at least better forms of Riba or interferon that will make life easier for those treating (which seem to be on the horizion). But until then, while these new drugs offer hope to some, and possibly an enhancement to many, they are not the silver bullet yet, that some might be hoping for. With each new chemical in the mix, I fear the perception of starting treatment, level of drop outs, and cost benefit (including financial), may get worse, not better.

[drofi]

Boceprevir resistant variants were
detected in the majority of subjects not achieving SVR:


BOCEPREVIR (B) COMBINATION THERAPY IN NULL RESPONDERS (NR): RESPONSE
DEPENDENT ON INTERFERON RESPONSIVENESS



E. Schiff1, F. Poordad2, I. Jacobson3, S. Flamm4, B. Bacon5, E. Lawitz6,
S.Gordon7, J. McHutchison8, R. Ghalib9, T. Poynard10, M. Sulkowski11,
C.Trepo12, M. Rizzetto13, S. Zeuzem14, P. Marcellin15, P. Mendez16,
C.Brass16, J.K. Albrecht16

1 University of Miami School of Medicine, Miami, Florida, USA;

2 Cedars-Sinai Medical Center, Los Angeles, California, USA;

3 Weill Medical College of Cornell University, New York, New York, USA;

4 Northwestern University, Chicago, Illinois, USA;

5 St. Louis University, St. Louis, Missouri, USA;

6 Alamo Medical Research, San Antonio, Texas, USA;

7 Henry Ford Hospital, Detroit, Mchigan, USA;

8 Duke University Medical Center, Durham, North Carolina, USA;

9 The Liver Institute at Methodist Dallas, Dallas, Texas, USA;

10 A.P.H. Paris, Hopital Pitie-Salpetriere, Paris, France; 11_Johns Hopkins

Univ, Baltimore MD, USA; 12_Hospices Civils De Lyon Hotel Dieu, Lyon,

France; 13_Opedale Molinette, Torino, Italy; 14 Univsitaetsklinikum Des

Saarlandes, Homburg/Saar, Germany, 15_A.P.H. Paris, Hopital Beauj, USA



Background and Aims: Boceprevir is a mechanism-based inhibitor of the
HCV-NS3 protease. We studied the efficacy and safety of boceprevir and
Peginterferon-alfa-2b (PEG-IFN-alfa-2b) in 357 genotype-1 ‘null’ responders
to peginterferon/ribavirin (P/R).

Methods: All patients had documented <2log10 decrease in HCV-RNA after 12wks
of P/R therapy or failure to achieve an undetectable HCV-RNA if treated more
than 12 weeks. All patients received PEG-IFN-alfa-2b (1.5µg/kg/wk) plus
boceprevir 100/200/400 or 800 mg po TID, or B400/R; the control was P/R/B
placebo with cross-over to active boceprevir (400/800) at TW17 for
detectable HCV-RNA at TW12.

Results: Safety analysis by independent Drug-Safety-Monitoring-Board (DSMB)
determined that

lower doses of boceprevir were less effective and resistance to boceprevir
was increased in the absence of Ribavirin (R). Therefore DSMB recommended
all patients who showed a viral response to boceprevir (HCV-RNA 24wks, with P/R/B800. Early response to therapy (HCV-RNA
Undetectable 36 wks were major factors
determining SVR. End of therapy (EOT) response rates ranged from 6%-32%,
being higher in the P/R/B400 and P/B800 groups and highest in control
patients who had boceprevir added to their regimen [14/34 (32%)]. Response

to the addition of boceprevir was evaluated in the control arm based on P/R
response at TW12; all 4 patients with a >2 log10 decrease at TW12 had
undetectable HCV-RNA on P/R/B, compared to 50% with a 1-2 log10 decrease,
and 20% of those with 2 log10 viral drop at TW12 may be good candidates for P/R/B800
therapy. Initial therapy with P/R, prior to the addition of boceprevir,
provides additional benefit.

[drofi]

Results: Safety analysis by independent Drug-Safety-Monitoring-Board (DSMB)
determined that

lower doses of boceprevir were less effective and resistance to boceprevir
was increased in the absence of Ribavirin (R). Therefore DSMB recommended
all patients who showed a viral response to boceprevir (HCV-RNA 24wks, with P/R/B800. Early response to therapy (HCV-RNA
Undetectable 36 wks were major factors
determining SVR. End of therapy (EOT) response rates ranged from 6%-32%,
being higher in the P/R/B400 and P/B800 groups and highest in control
patients who had boceprevir added to their regimen [14/34 (32%)]. Response

to the addition of boceprevir was evaluated in the control arm based on P/R
response at TW12; all 4 patients with a >2 log10 decrease at TW12 had
undetectable HCV-RNA on P/R/B, compared to 50% with a 1-2 log10 decrease,
and 20% of those with 2 log10 viral drop at TW12 may be good candidates for P/R/B800
therapy. Initial therapy with P/R, prior to the addition of boceprevir,
provides additional benefit.

[drofi]

For unknown reasons I can not copy the complete text, but it is cited in another thread:

http://tinyurl.com/58abvf

[willing]

drofi:
>For unknown reasons
I think you may be running afoul of one of the helpful improvements that have befallen this site of late. Terms that are recognized as medical keywords in posts are decorated with a "hoverize" feature (try hovering your mouse over a word with a slight dotted underline). As best I can tell this is thoroughly useless, but makes it impossible to reliably copy/paste text from posts You can work around it by using "View Selection Source" and then passing the html through a filter  that strips the span and hoverize tags.

willy50: >They seem to have the strongest proven efficacy.
putting aside the investment-related releases, which I think are less than useful, I'd be curious to know whether you saw any data that indicated superiority of telaprevir over boceprevir. I pored over this a bit (in the post drofi linked) when the easl abstracts first came out and it seemed that the RVR rates for telaprevir and the boceprevir with lead-in were near identical. Is new information available?