LATE BREAKING VX-950 PROVE I SUMMARY

Interim Results Presented at EASL from PROVE 1 Clinical Trial of Investigational Drug Telaprevir in Patients with Genotype 1 Hepatitis C

PROVE 1 data support potential to shorten treatment duration in treatment-na

[jmjm530]

PROVE 1 Summary

    * 88% and 79% of patients receiving telaprevir achieved a rapid viral response (RVR) as measured by plasma HCV RNA <30 IU/mL and <10 IU/mL, respectively, at 4 weeks.
    * Six of 9 patients in one treatment arm who completed 12 weeks of treatment, and who had achieved an RVR as defined by the study protocol (<10 IU/mL), continued to have undetectable HCV RNA 20 weeks after stopping all treatment (

[jmjm530]

Press Release here: http://www.vpharm.com/Pressreleases2007/pr041407.html

Investor webcast later today:

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

[copyman]

how common is a lung disorder called sarcoidosis with HCV? i seem to recall reading something about this or someone that posted here had this condition and thought they got it from HCV or tx? anyone ever hear of this or have information on this? thanks

[copyman]

sorry posted in wrong place. i was so excited reading the vertex news that i hit the wrong button

[jmjm530]

Not the silver bullet as many hoped for, but "ecouraging" in the words of Principal Investigator, John Hutchinson. It appears that 12-weeks of dosing is not going to be enough with the present protocol (Telaprevir, Peg, Riba) with efforts now going to concentrate on 24-week dosing in the future with and without ribavirin. It is important to note that what has been presented is for the 12-week dosing group only, and as many of us have predicted all along, the 12-week group was always the long shot with the 24-week group being the favorite.  Hopefully, the preliminary SVRs we've seen here from the 24-week group will be representative of the study in general. While not specifically stated, I wonder if the relatively low SVR rates for the 12-week dosing group will mean that Vertex will drop the 12-week group from future trials.

Here is how the 17 participants in Arm "D" did:

Analysis of PROVE 1 Patients who Finished All Treatment at 12 Weeks
Seventeen of 175 patients received at least one dose of telaprevir in

[jmjm530]

Maybe a little too quick in the above post to dismiss the 12-week dosing approach entirely. In the subset of those who were non-detectible at week 4 and continued to be non-detectible at week 10, 66% (6 of 9) were still non-detectible 20 weeks post treatment. So, it's possible that for certain patient sub-sets, 12 weeks might be an option to consider, especially if they are having a difficult time with side effects. Still, doesn't look like 12 weeks is going to be the general approach for now.

[Sincebirth]

Looking at the data:

Arm D
Total patients = 17
Adverse events patients = 4 of 17 (24%) (But only 11% for whole study group)
RVR patients = 9 of 17 (53%)
RVR patients that achieved SVR20 = 6 of 9 (67%)
Total patients that achieved SVR20 = 6 of 17 (35%)
Total patients that potentially could have achieved SVR20 = 10 of 17 (59%)  These additional 4 patients did not stop treatment and could have potentially achieved SVR if stoped treatement.

Basically we are looking at a SVR rate of 35% to 59% for 12 weeks of treatment.  Probably closer to the 35% range.

I think this is about what everybody expected for the study.  I am personally pleased with these results and indicates good effectiveness of the drug.

Keep in mind that these percentages dont really reflect the general HCV infected public because the patients that Vertex selects for the studies are "hand selected" to potentially have higher SVR rates.  (i.e. Low initial HCV RNA count and other specific criteria)

This is also VERY important:

"""The most common reason for treatment discontinuation in the telaprevir arms was rash (7 patients), and the median time to discontinuation in these patients was 64 days."""

64 days (9 weeks) is when most people had to go off the drug due to the rash.  This is important because the patients that got the rash, most experienced it early and did 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 11% for the duration of treatment. Meaning 11% of people that use VX get the rash. And you just need to monitor people in the first 12 weeks of treatment.

[Willy50]

You are fast on the draw........

We are now how many years past the introduction of pegalated interferon and only recently have they been really looking at the notion of RVRs and building treatments around response.  Only until very recently have they started abandoning the notion of a one size fits all treatment.  How many who have treated SOC have gotten a PCR at 4 weeks?

When certain groups respond and clear in days.....not weeks, I think it begs the question as to whether new tiers for treatment legs are needed.  Could the same methodology which recommended shortening geno 1 RVRs be further applied to people who clear in days?  That group could conceivably treat for 12 weeks.  A different treatment protocol could be formulated for those who manage to clear in 2 or 4 weeks (and longer).  

This is just a study.  It is very ridgid.  If a study were contructed where groups were all treated with triple dosing and THEN put into appropriate SOC trial durations based on the initial response we might see a different response rate without reformulation of any drugs.

Once they figure out the proper trial durations and dosing I think we'll see improved results.  When the upcoming Prove 2 trial results show the role of ribiviren we may also find that some people can be treated without it...... but that to be safe we may need it during the critical 4-6 weeks.  If that means that some rash issues could be avoided and the drop out rate could improve.

For me it is not a home run but I feel as if we are only in the second or third inning of the game (for crying out loud).  We really still don't have complete Prove 1 results, and no Prove 2 or 3 results.  

I believe they will be able to find that happy compromise where they will be able to shorten treatment, improve SVR rate and reduce side effects.  The "side effects" may be reduced either in the sense of severity or in duration. (24 versus 48 weeks of side effects)  

Finally, there is a question of balancing the inherent sides of TVR and SOC (that we don't yet know against the side effects of) against 48 weeks and longer SOC treatments that many of us are faced with.  Many people suffer permanent and longish term sides from SOC that could be avoided with a shorter treatment.  Think also of how many people will be saved from advancing HCV related liver damage if the "cure" rate was increased from the 40-50% we now see to a 75% cure rate.  A  75% cure rate with a shorter treatment may be a "home run" to many of us that face declining health time to treat our HCV.

best,
Willy

[jmjm530]

Since,

Yes, I think the "Street" was projected to be happy with 40% although frankly I'm surprised they didn't wait to release this data with the upcoming 24-week data. Maybe they had committed to this before seeing the results or the disclosure was regulated. The other thing about the "rash" appearing somewhat uniformly at 9 weeks, may be future trials shortening the VX-950 dosing to avoid the rash and/or coming up with effective solutions for the rash.

Willy,

Yes, it's all a balance and while we'd all like a magic bullet, shorter treatments with higher cure rates is what we need and what we appear to be getting. It's also important to keep in mind that this is just the beginning for this entire category  of drugs, with more PI's on the way, and no doubt future trials combining different PI's with and without interferon. Certainly no need for anyone without significant liver damage to necessarily change their watch and wait strategy, but at the same time it should give them hope that significant progress is being made.

-- Jim

[Willy50]

Fast forward for a few weeks.  Some of these folks will have "official" SVRs (they only have 20 weeks in at conference time).  4 are still treating but presumably have not rebounded.  They may yet finish and retain an SVR.  They are still included in the denominator and so therefore it would appear that the success rate can only move upward.  (correct me if I'm wrong)

I thought that the denominator would remain at 17 since the one (even though they withdrew) still received one dose.  I think this is one area that people might argue whether the denominator was 16 or 17.

Did I hear some mumbling about the 3 who discontinued due to sides?  That maybe some were still clear of the virus but were not counted since they withdrew from the study?  You'll notice in the 4 and 12 week comparison table that is why the TVR success rate dropped from 79% at week 4 to 70% at week 12; is was due to the withdrawal of the 3 trial participants.

Thanks for the discussion of this.  It helps make it easier to digest and understand the process involved.

I think this has been a good day for all of us.

Willy

[jmjm530]

Since: So we are probably looking at a bare bones minimum SVR rate of 45 to 50% for 12 weeks of treatment.
-----------------------------------

I agree that it's hard to draw conclusive SVR data from such a small group, but I don't think you can make the statement above, based on what we have. First, you do have to take into account drop-outs due to side effects; and second, if by "bare bones" you mean not counting the 4 that are continuing on -- these four can no longer be construed as part of the 12-week dosing group since they are dosing longer. I think the "35%" SVR figure originally mentioned is more reflective of what we have now. I do share your excitement regarding the potential with the 24-week arm.

-- Jim

[Sincebirth]

I agree that we have to take the drop outs into account, but the 3 drop outs are due to refusing consent, acid reflux, and Anemia.  At least two of these I consider not relevant because Anemia can be treated when not in a trial setting and consent is a personal issue.  Unless acid reflux is a common new side effect of VX that it may be an outlander that can be excluded as well

That is why I used 14 for the denominator.

[jmjm530]

Reflux is common and it personally was my bane during treatment and the lack of the rescue drug from Procrit (epo) may be balanced out by the hand-picked nature of the group. Given the "lack of consent" drop out, maybe we can split the difference between the two figures then (35% - 45/50%) but such a small group it could go either way. The 24-week data seems to be the key and we both seem to be optimistic on that. Curious, what are your stats and what stage of the treatment process are you in. I'm a previous 1B who treated for 54 weeks and have been non-detectible for a little over a year.

All the best,

-- Jim

[Sincebirth]

Jim thanks for your response,


"""" if by "bare bones" you mean not counting the 4 that are continuing on -- these four can no longer be construed as part of the 12-week dosing group since they are dosing longer""""



Yes that is what I meant.  Maybe I am being optimistic but my reasoning is that some of these 4 may have become SVR if they stopped with the other 9 that had RVR at week 4.  

For instance lets say 2 of the 4 got undetectable at week 5 instead of 4.  Following the study protocalls they would not have stopped treatment.  But they could have still potentially still achieved SVR if they did.  We will never know.  So the "potential" rate could have been higher.

Is that making sense or am I missing something?

Thanks

Darryl

[Sincebirth]

We seem to be crossing posts

"""Curious, what are your stats and what stage of the treatment process are you in. I'm a previous 1B who treated for 54 weeks and have been non-detectible for a little over a year. """"


My stats are

33 year old male
HCV 1a due to blood transfusion at birth
On treatment - week 64 of 72
Stage 2

Undetected at week 28 after swiching interferions at week 16.  Fairly Rapid viral drop after switching interferons.

[jmjm530]

Yes, you definitely make sense. Good point!

All the best with your treatment.

-- Jim

[Sincebirth]

Some interesting points from the webcast:

My interpretation of Arm D data after web cast:

I jotted this down from one of the slides

Total patients = 17
1 withdrew consent
Total patients on treatment = 16

Out of these 16 patients, 3 stopped treatment -  1 relapsed, 1 had acid reflux?, 1 had bad anemia.  

That leaves 13 patients that completed 12 weeks - 4 did not achieve RVR at 4 weeks and continued treatment.

So now down to 9 patients that had RVR and 6 went on to achieve SVR 20.

Hutchinson said it is very hard to determine a SVR percentage from this data because it is such a small subset of patients and there are too many variables of patients that "could" have achieved SVR that stopped treatment.  And some (4 patients) are still on treatment.

But if you disregard the patients that had Acid reflux, Anemia, and withdrew consent you now have a subset of 14 patients.  6 of 14 went on to achieve SVR.  (43% SVR)  And 4 additional patients are still on treatment that could have potentially achieve SVR.  

So we are probably looking at a bare bones minimum SVR rate of 45 to 50% for 12 weeks of treatment.

I am very excited to get the 24 week treatment arm data.  

[APKhaos]

sincebirth said, "Keep in mind that these percentages dont really reflect the general HCV infected public because the patients that Vertex selects for the studies are "hand selected" to potentially have higher SVR rates. (i.e. Low initial HCV RNA count and other specific criteria)"

Just wondering about your basis for this assertion. I have nothing to refute it, other than a single data point, which happens to be my own:

- Initial HCV RNA count 26,400,000 , which is hardly in the 'low' category
- Stage 3 liver histology
- 30+ years since initial infection

As I understand the selection process, its the individual clinics that make the selection based on trial criteria, but without reference to Vertex. Clinics may seek waivers of certain trial selection criteria. The waiver requests go to the Chief Investigator for consideration. Its not clear if Vertex gets involved in these waiver decisions. Even if they did, the waiver cases are very rare, according to the clinic I attend for the Prove 1 trial.

You may well have other info, but that's what I've seen as a subject in the trial.

[Willy50]

First, APK I apologise for miss-typing your "name" in another thread by PLN where I referred to you as APL  (the keys are close together and the fingers were flying).  I also misrepresented your starting viral load as 28 million but the log drop issue remains about the same; what's 1.5 million IU/ml between friends?

Since Birth, I agree with APK on this one.  I think that the FDA regulates the structure of these trials so that the very thing you are referring to does not happen.  It would be far too easy to "cook the books" otherwise.

Chcnme just posted a useful interview with several responses by Vertex officers which indicate  that not only do they not get to choose or decide...... they also don't have the results of the trials themselves at various stages of the trial progress.  If we are frustrated by lack of information perhaps they are too.  : )  It also begs the question; if the information is kept blinded then perhaps boards such as this may also serve as a more useful (although anectdotal) source of information; not only to us heppers or investors but to doctors and drug companies alike.  That may be a stretch but I don't know when (in this case) Vertex is given the information by the folks running the studies.

Oops; here's that link provided by Chcnme; (by the way...thanks)
http://seekingalpha.com/article/25843

The thing in this interview that caught my eye was that there was virtually NO exclusion factors from the Prove 3 study.  Generally, all you had to do was fail (current) SOC once before; they would take all variety of failures.

best,
Willy