Cr Hutchison's EASL abstract Part 2

[APKhaos]

Results: The total incidence of adverse events was similar in the control and TVR/PR groups (75% vs. 80%). Discontinuations due to adverse events were more frequent in the TVR/PR group (9% vs. 3%). Rashes were more common and some were more severe, and gastrointestinal (GI) events were more common, in the TVR/PR group. In subjects for whom results were available at Week 12, the proportion of subjects with undetectable HCV RNA at Week 12 was 88% in the TVR/PR group, and 52% in the control group (p=0.0001). (Taqman assay: LOD 10 IU/mL).
Conclusions: TVR/PR produced a higher frequency of HCV RNA undetectability than Peg-IFN-2a/RBV alone, in this 12-week interim analysis. The adverse event profile was similar in type of events, but rash and GI events were more common in the TVR/PR group. The Independent Data Monitoring Committee reviewed the data and recommended no changes to the study. An interim analysis, including data up to 12 weeks on-study in all subjects, as well as SVR12 data in subjects who have stopped all treatment at 12 weeks or earlier, will occur in March.
* PROVE1 Publication Committee, for the study team.

[chcnme]

Thanks so much for your input.  I arrived back from out of town just in time to listen to the webcast.  - in the NICK of time :)  

You guys have great day.    

APK - I'm glad you invested; glad we didn't sell - patience is a virtue.

[jmjm530]

The late breaking report hasn't tempered my enthusiasm for Telaprevir at all, but I don't think you're going to clean up in the market based on the 12-week
results :) But then again, I'm usually wrong on which way the market reacts.
Be well,

-- Jim

[jmjm530]

What if the article said that investors would be happy if VX-950 cured Hep C in 80-90 per cent of geno 1's with only 24-weeks of treatment? I think the 12-week expectation numbers are misleading because Vertex is being tested for 24 weeks as well and 24 weeks may well indeed be the magic bullet, or as magical as we can have it with this new generation of treatments.  Anyway...I think this will be my last post on this topic until after the late breaking oral presentation tomorrow.

-- Jim

[jmjm530]

It appears there will be 8 late-breaking presentations on Saturday, with the Vertex presentation being the last one at 5:45 local Barcelona time, 11:45 Eastern Time with data under "embargo" until the conclusion of the presentation which should be 12 Noon Eastern Time on Saturday (tomorrow). Then, an hour and half later (1:30 EST)Vertex will have a live investor webcast accessible on the Vertex web site.

-- Jim

[nygirl7]

Has anyone been on this drug for more than a year so that we COULD see how the SVR appears to be going?  UND is a great thing but we NEED to see is SVR.

ARGH!

And - do they think it's worth reformulating to get rid of all of the serious sides AND will that mean it's like a start over do over situation where they start from step one in the approval process with the FDA?

While an almost 10% drop out rate isn't THAT high "SOUNDING" it is very significant.

These are the things that I NEED TO KNOW!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

IT'S SO CONFUSING TELL US IN ENGLISH!!!!!!!!   ;)

[jmjm530]

"...We view the home run scenario of 75 percent SVR rate for telaprevir for only 12 weeks of therapy as possible but a long shot," Piper Jaffray analyst Rachel McMinn wrote in a research note. "We view an SVR rate in the 40 percent to 50 percent range as more probable."

Cowen and Co. analyst Phil Nadeau said investors are likely looking for at least a 40 percent sustained response. "If you see over 40 to 50 percent, people will be happy; less than 40 and people will be somewhat disappointed," he said....

http://www.reuters.com/article/ousiv/idUSN1034597520070410?pageNumber=1

[jmjm530]

Just to clarify, the analyst above is comparing SVR rate expectations for 12 weeks of VX-950 against 48 weeks of SOC. Apparently, they feel that if VX-950 matches SOC's SVR rate for geno 1's (40-50 per cent), then it will be a success. I don't think many of us would disagree. No comment was made on expectations for the 24-week dosing group, but that data doesn't look like it will be released yet.

[Kalio1]

happy with a 40% sustained response? Huh? SOC has better SVR rates, why would that make anyone "happy?"

seems to me the old adage "good news travels fast" applies here, if they had good news, they'd be sharing it.

Still no SVR data, gimme a break.

[jmjm530]

The reason they would be happy with 40-50% SVR is that you're getting the same SVR rate for geno 1's as with SOC. The difference, however, is that you're only treating 12 weeks instead of 48. Keep in mind that this expectation is only for the TWELVE WEEK GROUP. I would guess that the expectation for the 24-week group would be closer to 75-85 per cent SVR. That would be almost double the SVR rate in half the time compared to SOC. If that's not a breakthrough, not sure what is. Let's just hope that these expectations bear out. So far no formal SVR data has been presented and hopefully we'll get it tomorrow.

-- Jim

[chcnme]

This is like a full-time job (worse) trying to figure out what they're saying or what the data they are presenting means.  I read the 40% stuff a few days ago  (that this would be considered "good news")  and thought the same thing. I guess I'm expecting some marvelous, "conclusion" or one-paragraph in one poster presentation that says something similar to what all the top dogs and what's-his-name CEO Boger were saying 3 months ago - or however long they've been touting, ya know?  Oh let me shut-up. And what's even worse - none of my docs (Duke doc included)  will say a word about their opinion, or  - if they do - it sure isn't ranking up there with "oh we are jumping for joy at Vertex".  Hep C sux.  Bye ya'll - I'll be back later to read. Guess I'll go get some of that wonderful stress relieving exercise I need.

[jmjm530]

Maybe our posts crossed but wouldn't you think that similar geno 1 SVR rates (40-50 per cent) in ONE THIRD THE TIME would be great news? And remember, they're only talking about expectations about the 12 week group, I'm sure the expectations will be higher for the 24-week group. Of course, we're all looking for the magic bullet but any significant difference in treatment results/duration should be applauded and I think what the analysts are discussing would be "significant" by any measure. Hopefully tomorrow's presentation will bear out the expectations, right now all any of us are doing is speculating.

-- Jim

[chcnme]

Yeah our posts did cross.   I guess I'm just a little worried - that's all.  I think it would be OK news but not necessarily great news, especially in light of the rash and GI sides that will occur within the first few weeks in some who will opt to treat with VX (and will have to stop treatment on account of those sides) in what we've been hoping will be a shorten duration of treatment with VX  (and I've been hoping for one with a more powerful punch than a reported 40 - 50%.)   VX has gotten huge applauses from me for years up until this time, and I think my frustrations now (or lack of applause on this particular note) is a combination of being tired of waiting, and tired of waiting for the data on VX, anticipation, anxious,  etc., and just hoping it'll be good data and what I've wished for -- something that will give more assurance that it's been worth the wait and that it's STILL worth waiting for another year or two.   Yep - that magic bullet would be nice, and for now - it's all speculation, but back to the 40% - for patients and investors that's OK news, and it'll do, but it's not what I consider *great* news. Maybe I'm expecting too much too early. I'll  just sit on  my hands until the data is in and hope for the best :)

[chcnme]

Thanks APK.  I am getting kind of lost trying to keep it straight in my head on what's going to be reported on, but I guess whatever it is the wait will be over with by Saturday :)

If this (below) has already been posted somewhere (I looked but didn't see it anywhere, but it was a real quick look).  Does anyone know (or wonder) why VX-950 presentations are being done as "late breakers" on Saturday?   Are there other late breaker presentations or have the late breakers been reserved exclusively at the EASL for Vertex?  Just curious.  
=====================================

Press Release Source: Vertex Pharmaceuticals Incorporated

Vertex Pharmaceuticals Announces New Data for Investigational HCV Protease Inhibitor Telaprevir to be Presented at 42nd Annual Meeting of the European Association for the Study of the Liver (EASL)
Wednesday April 11, 8:30 am ET  
In vitro results support expansion of telaprevir clinical development into genotype 2, 3 and 4 HCV patients


BARCELONA, Spain--(BUSINESS WIRE)--New data supporting the clinical development of telaprevir (VX-950), one of the most advanced investigational oral protease inhibitors for the treatment of hepatitis C virus (HCV) infection, will be presented at the 42nd Annual Meeting of the European Association for the Study of the Liver (EASL) in Barcelona this week. In total, nine abstracts related to telaprevir have been accepted for presentation at the EASL conference, including an abstract that describes telaprevir activity against genotypes 2, 3 and 4 in vitro. A late-breaker oral presentation will take place on Saturday, April 14 at 5:45 p.m. Central European Summer Time (11:45 a.m. Eastern Daylight Time). Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX - News) is developing telaprevir in collaboration with Tibotec.

"Hepatitis C is a major global health problem with a significant unmet medical need. Despite treatment advancements in the last 10 years, there is an urgent need for new therapeutic options that can offer patients shorter course therapy and better efficacy," said John Alam, M.D., Executive Vice President, Medicines Development, and Chief Medical Officer of Vertex. "The data to be presented at EASL demonstrate the recent progress made in our clinical evaluation and understanding of telaprevir as a novel treatment for hepatitis C, underscoring our commitment to evaluate telaprevir's potential in important sub-populations, such as those with genotype non-1 hepatitis C."

Telaprevir is one of the most advanced specifically targeted antiviral therapies for HCV (STAT-C). STAT-Cs represent a new approach to hepatitis C treatment by directly targeting the enzymes the virus uses to replicate.

Oral Presentation: Telaprevir Demonstrates Potency Against Genotype 2, 3 and 4 in vitro

Chao Lin, Ph.D., of Vertex, will present an abstract titled, "Telaprevir (VX-950) is a Potent Inhibitor of HCV-NS3 Proteases Derived from Genotype Non-1 HCV-Infected Patients" at 6:15 p.m. CEST (12:15 p.m. EDT) on Thursday, April 12.

"While genotype 1 accounts for the majority of hepatitis C cases, the proportion of those living with genotypes 2, 3 and 4 is significant," continued Dr. Alam. "In this in vitro study, telaprevir demonstrated similar potency against the NS3-4A protease derived from those patients with genotype 2, 3 and 4 to the in vitro results demonstrated with telaprevir in genotype 1. These results support our plans to begin to study telaprevir in genotypes 2, 3 and 4 in 2007."

Late-Breaker Presentation

A late-breaker presentation titled, "Results of an Interim Analysis of a Phase 2 Study of Telaprevir (VX-950) with Peginterferon alfa-2a and Ribavirin in Previously Untreated Subjects with Hepatitis C," will be presented by John McHutchison, M.D., Principal Investigator for the PROVE 1 study and Director of Gastroenterology and Hepatology Research at Duke Clinical Research Institute, on Saturday, April 14 at 5:45 p.m. CEST (11:45 a.m. EDT).

In accordance with EASL embargo policy, these data remain under embargo until conclusion of the late-breaker session on Saturday, April 14 at 6:00 p.m. CEST (12:00 p.m. EDT).

Additional Telaprevir Presentations

Additional data presented at EASL will include viral kinetic data that continue to support further evaluation of telaprevir-based therapy to clear the hepatitis C virus with shorter treatment duration, and in vivo and in vitro viral replication and viral sequencing dynamic modeling studies that suggest telaprevir-resistant variants have reduced replication capacity compared to wild-type HCV. Poster presentations will begin on Thursday, April 12.

"Novel Mode of Viral Decline During Telaprevir (VX-950) and Peg-IFN Combination Treatment Predicted by a New Combined Intracellular and Cellular Hepatitis C Viral Dynamics Model," will be presented by A.U. Neumann of Bar-llan University, Israel.
"Telaprevir (VX-950)-Resistant Variants Exhibit Reduced Replication Capacity Compared to Wild-Type HCV in Vivo and In Vitro," will be presented by Chao Lin of Vertex.
"Ultrasound Evaluation of Perihepatic Lymph Nodes During Antiviral Therapy with the Protease Inhibitor Telaprevir (VX-950) in Patients with Chronic Hepatitis C Infection," will be presented by Mireen Friedrich-Rust and Nicole Forestier, Saarland University Hospital, Germany.
"Neopterin and ALT as Markers of Inflammation in Chronic Hepatitis C Patients During Administration of the HCV NS3-4A Protease Inhibitor Telaprevir (VX-950) in Combination with PegInterferon Alpha 2A," will be presented by Huub Gelderblom, University of Amsterdam.
An oral presentation titled, "Molecular Basis for VX-950 Resistance," will be presented by Stefan Zeuzem, Saarland University Hospital, Germany, at 5:15 p.m. CEST (11:15 a.m. EDT) on Friday, April 13.
Two presentations discussing in vitro data of telaprevir in combination with other oral direct antiviral therapies will also take place during EASL.

Full abstracts are available on the EASL website: www.easl.ch/liver-meeting.

Webcast of Investor Presentation

Vertex intends to provide a live webcast of its investor presentation from Barcelona beginning at 7:30 p.m. CEST (1:30 p.m. EDT) on Saturday, April 14. The presentation may be accessed from the 'Events Calendar' on the homepage of Vertex's website at www.vrtx.com. A replay of the webcast will also be available on the Company's website until April 27, 2007. To ensure a timely connection, it is recommended that users register at least 15 minutes prior to the scheduled webcast.


continued....
http://www.vrtx.com/Pressreleases2007/pr041107.html

[Sincebirth]

All of this is confusing so I have some questions about data to be release for tommorow.

Question1 -- Will we get tomorrow SVR (12week) data, SVR (24week) data or just undetectable status at end of tx.

Question 2 -- Specifically which group or groups will data be given for?
Will data be given for people doing VX-950 + SOC for a total of 12 weeks?
Or for people doing VX-950 + SOC for 12 weeks plus 12 week SOC follow up?

Thanks,

Darryl

[nygirl7]

There is no real SVR data at all.  

SVR is the goal not UND.  We don't know yet if using a drug to falsely manipulate an UND (which is not neccesarly a REAL UND where you KNOW no virus is left anywhere) wont end up backfiring in the fact that without the "extra" weeks of treatment - we won't see many many relapses because the virus is still there.

If we have real SVR info that is different.

"Maybe our posts crossed but wouldn't you think that similar geno 1 SVR rates (40-50 per cent) in ONE THIRD THE TIME would be great news?"

Not when the drop out rate went up so greatly.  


A lower SVR rate with a higher drop out rate versus a higher SVR rate with less drop out rate.  That to me is the better option even if people have to treat longer. The GOAL is to achieve - not to do it as fast as possible.

That's my only real point.  Hoping for a 40% SVR rate and treating for less time?  Heck we could do that NOW by having geno 1s just treat for 24 weeks.

Right?  

[chcnme]

Me too, Jim  (just going to wait and try to decipher it and then form an opinion.)  

I want to ask something, though  (on what APK posted).    And I'm also looking forward to anyone who has an answer to sincebirth's questions.

On what APK posted, it says  (at the end)  "The Independent Data Monitoring Committee reviewed the data and recommended no changes to the study."

QUESTION:  Is this IDM committee part of the FDA's "fast track" or part of the FDA's "overseeing" committees (for lack of better words)  or part of the New Drug Application with the FDA, which VX announced a while back they already filed for -- do you know?

And then it says "An interim analysis, including data up to 12 weeks on-study in all subjects, as well as SVR12 data in subjects who have stopped all treatment at 12 weeks or earlier, will occur in March."

QUESTION:   That sentence is confusing me.   What does "12 weeks on-study" and "SVR12 data"  mean.   Are they saying they are going to be reporting something in March 2008 from the PROVE1 one study - still?  As if... we have to wait until March 2008?

lol - I will totally understand if you don't want to attempt to explain.  

[Willy50]

Darryl, I don't know if anyone knows positively.  They may NOW know just 24 hours before the presentation but I sure don't know.  Vertex has for certain said they would present information about the group of 20 trial participants who treated for 12 weeks with TVR, Interferon and Ribiviren and then stopped all treatment.  I believe that they will have "official"  6 month SVR rates, drop out rates, etc for that group.  All that I have heard is that they are only talking about that group.  The rationale I believe is that is the only group that they have complete information on.  (this really isn't true since there were about 24 people who treated in early 2006; 12 with monotherapy and 12 with TVR, interferon and ribiviren.  I believe that some of that group were given the choice of continuing with SOC.  At this point those folks would be done with any treatment and have 6 or 9 month SVR's.  I've heard no word on what happened to these folks and whether they will be mentioned.

It's true that Vertex has lots of other partial information but their pattern has been not to share it until it is complete.  That means we may not see or hear information about the Prove 1 arms that treated for 12 weeks with triple and then followed up with SOC (of various lengths of time).  It is also possible that they will not share information on the Prove 2 no-ribiviren arms even though they would also likely have the results of the first 12 weeks of treatment with TVR and Interferon ONLY.  There were 80 people in that arm I believe and so they really have quite a bit of data.  Vertex has mentioned that the ultimate SVR rate that is associated with the use of ribiviren correlates to the anti-viral response rate in the early weeks of treatment.  This means that if people respond quickly and completely the liklihood is that the antiviral response will be durable.  In this sense they have a good tool for predicting the SVR rate based on the early results of the trial.  My guess however, is that it is too early to provide theory and hypothesis.  Vertex will only be providing scientific data and results (complete results; not partial) : (

The stock itself has done a bit of a nosedive today.  It has dropped about 7.5% at the time of this posting.  What does that mean?  I've no idea.  One possibility is that there is will be less news at the conference than was desired.  It could signal mixed results of trials.  I think that some of it was that investors are still acclimating to the notion that there won't be a "home run."  For me the prospect of possibly cutting the treatment in half or to a third of the duration sounds very good even at the same cure rate.  Keep in mind, this is still only Phase 2 and the very earliest results of the first large trial.  Efficacy rates and treatment times could still be further improved and refined.  

IF the efficacy rate shows that (for instance) ribiviren could be reduced in duration or dosage some of the side effects could be eliminated.  ALSO remember that although the dropout rate was triple in the TVR arm compared to the SOC arm in the first 12 weeks the yearly drop out rate for SOC is about 13% whereas the Vertex arm was 9% in 12 weeks.  

Even after the EASL is over there will simply be new questions, new interpretations, new gripes about not enough information.  It's a drag but I hope they throw us a few crumbs of information this weekend so we can keep our hopes up while we bide our time waiting for the next release of information.

best,
willy

[Sincebirth]

I agree with you nygirl that ultimately SVR is the goal.  But the good news if the 12 week arm has a 40 to 50% chance of svr is that one could conclude that 24 weeks or 48 weeks of Vx+SOC would result in a much higher SVR rate potentially 70 to 90%.  

Personally I really only care about getting rid of the virus and treatment time is a secondary concern.  But the implication of better success for shorter treatment indicates better success for longer treatment.

I would look at 40 to 50% SVR 12 as good news.  

I am currently on week 64 of treatment going 72 weeks (like you).  I consider myself pretty tough and detemined.  Will try to tough out 24 or 48 weeks of VX if neccessary to finally achieve svr.

[Sincebirth]

I agree willy.

SIDE EFFECT DISCUSSION:
The REAL deal breaker info for this drug will be the side effect news.  The 12 week drop out rate of 9% on VX compared to 3% SOC.  If all of these people dropped due to the SEVERE rash, that could be bad news.  

Hopefully they will give data that individualizes the reason for drop-out.  If it is for normal SOC sides than that would be good news because rescue drugs can be administered when not in the trial setting resulting in a much lower drop out rate.  

It would also be interesting if the patients that got the rash all experienced it early and not acquired the rash at different random times through the duration of treatment.  That could indicate that "If you get the rash, you will know early" and the drop out rate would probably stay around 9% for the duration of treatment.  Meaning 9% of people that use VX get the rash.  If people started getting the rash after the first 12 weeks we may see a much higher drop out rate than 9% for longer VX treatments.

VIRAL SVR DISCUSSION:
Knowing the way this virus spreads through the body, I will be surprised if 12 weeks of any treatment will give higher SVR numbers.  That is not enough time for eliminating infected hepatocytes for most people.  Some people the infected hepatocytes can last for 60 weeks before releasing the virus.  I don

[Sincebirth]

I am going on record with some predictions for this drug.  No real medical knowledge here just a lot of reading and hunches!

Hunch 1 - My prediction is that we are looking at 12 weeks of VX+SOC treatment for those of us that are natural rapid responders with 80 to 90% SVR.  These are the people that would usually be undetectable at week 4 on SOC.

Hunch 2 - For those of us that would usually go 48 to 72 weeks we are probably looking at 12 weeks of vx+SOC then an additional 12 to 24 weeks of SOC.  Total treatment time 24 to 36 weeks.  (70% SVR).  

The problem is that with VX it is so powerful you would not know if you are a natural rapid responder.  The drug knocks down the blood borne virus so quickly there is not enough information to gleam any meaningful viral kinetics and therefore would be taking a risk not treating longer than 12 weeks.

Hunch 3 - VX will only be dosed for the first 12 weeks and SOC for some time after.  It seems the drug is good for knocking down the virus quickly but you need the interferon to finally kill it for good.

Hunch 4 - Rash sides affect 10 to 15% of patients and have to go off treatment.  Patients will have to be monitored closely during initial treatment.  The sides may affect Vertex's fast track status of the drug and Phase 3 trail data may have to be provided before FDA approval.  

Hunch 5 - Ryba will need to be administered with the cocktail but at a lower dose.  And VX will be administered twice daily (BID).   These will ultimately help with the rash sides.

Again just speculating.

[APKhaos]

Some strong analysis here! Just read quickly, so I may have missed some nuances.

The timing is the thing.

ARM B - 12 weeks of VX+SOC is the only arms where there has been any significant post-tx data available sufficient to report SVR numbers.

pln and I are at the sharp end of the Arm C cohort - 12 weeks of VX + SOC followed by 12 weeks of SOC. Our 12 weeks post-tx lab results came back just this week, so its hard to imagine that a large enough subset of Arm C subjects are at 12 weeks post-tx. Even if there were, the data became available much to late to be analysed, reviewed, and published in time for presentation at EASL. The US conference late in the year is a likely time for some insight into SVR from our group.

As for the street, who would know? I'd think that 80% SVR with 24 weeks [12 VX+SOC, 12 SOC] of treatment would very likely result in this becoming the standard of care. Lifting the clearance rate from 50% to 80% with HALF the length of treatment is a step forward in the treatment of HCV, right?

An 80% SVR with just 12 weeks of treatment would be very remarkable, but its almost to much to wish for when treating a virus that has as many tricks as the this does.

The data is not yet available to tell which of these outcomes, or another unanticipated outcome, is likely. Its frustrating, but there really is no other way.

[jmjm530]

Your hunches are in line with my thinking, but I think they will be able to target RVRs with VX-950 by the use of earlier and more frequent vl testing. Hopefully the current study data will lead the way and/or follow-up studies will no doubt explore this angle. Of course, all speculation, cause if I knew for sure I'd be buying up the stock right now, and I ain't.

-- Jim

[APKhaos]

Full Disclosure: I finally broke down and bought VRTX recently, while it was bouncing along the high 20's. C'mon in Jim, the water's....um.....indeterminate, because the temp control is being managed by a bunch of manipulative trolls without a clue and with a short attention span. It was ever thus.

[miked]

I already knew this?

Like Jim asked, "Will they be releasing SVR data?"  Anyone know anything?