VX-950 combo trial starts in Europe

VRTX announced yesterday that the combo trial of 950 and interferon has started in Europe. This is in geno. 1 treatment naive patients, as opposed to the other trial which had many which failed current treatment. 8 will receive 750 mg 3x daily, 8 750 3x daily plus interferon, and 4 interferon only. Expect top line results early in the first quarter of next year. An IND will be filed with the FDA in the next few weeks to start Phase II in the states here by the end of the year, which will be combo treatment.
For a refresher, VX-950 alone dosed 3x daily at 750 mg saw a mean 4.4 log drop in 2 weeks. Half went undetectable between days 11 and 14. Rule of thumb is that complete treatment should take 3-4 times as long as it took to go undetectable, which is why trials are so short. Also, this trial will use the pill formulation instead of the oral suspension in the prior trial. The pill has shown greater bioavailability. The prior trial it was taken on an empty stomach. They said something (webcast is archived, I need to go back and listen again) about this being taken with food which increased blood concentrations 2-3 times.
A 3 month monotherapy trial is planned for early next year.  

Prudential is hosting a call at 1:30 ET today with a co-author to some abstracts on Schering's drug and VX-950 using AASLD info. I am not a client of theirs, so I won't know what happens unless someone posts it on the VRTX message board.

Feel free to hijack this thread.

[jmjm530]

Thanks for the update. In the states I believe they started with treatment naive, it appears from what you say the opposite in Europe.

I'm interested in the "rule of thumb" you mention where treatment extends from 3 to 4 times the amount of time it takes to get non-detectible. Do you have any more information on this?

I believe I've heard this before but maybe it's just a Vertex rule of thumb and wondering how they came up with it, since I don't believe the trials have gone to SVR yet.

For example, I'm a geno 1 and cleared at week 6. By the "rule of thumb" formula, that means I would only have to treat 18 or 24 weeks. And while a European commission has adopted a 24-week program for selected geno 1's, the operative word is "selcted". They had to clear by week 4 and have a pre-tx viral load under 600,000.

That said, I really am rooting for this new drug. If their formulations are correct and half went undetectible within two weeks, then that half  will only need to be treated in 30-60 days. Wow!

-- Jim

[mom4two]

WOW! anybody have any idea how long the trial will last and if all goes well, when to expect FDA approval. I just tested posivtive for hep c and confirmed genotype 1a.  Depending on liver biopsy, I was considering tx next September.  If this drug could be an option I would considering waiting another 6 months to a year.

thanks,
Lori

[couldn't think of a nickname]

actually, the first trial was in Europe also, as none have started yet in the states. That is scheduled to happen by the end of the year though. According to their web cast yesterday, this second study will be all treatment naive patients (they gave a reason, I don't remember what it was). The first one did have many non-responders in it. Maybe this has all treatment naive because they want to measure it where there wouldn't have been any resistance to interferon (just my guess). I guess it makes sense too, since the first one was the opposite.

That rule of thumb is interesting, and I had not heard it until I have heard them talk about it. They point to studies that show EVR can have shorter treatment times-geno 2's who clear at 4 weeks, treat for 3 months, and maintain SVR. They also point out the established medical opinion that undetectable at week 12 requires 48 weeks of therapy. They only plan to use 950 in conjunction with the best antivirals in the market or in testing, and right now, that is still interferon. I guess it doesn't make sense to use it with anything but no. 1. It also sounds to me like ribavirin might not be used, and I think that in itself is big. I am sure you can testify to the hell that can cause.

To make the "wow" bigger, it probably is not a leap to hypothesize that the results with the additive (and possibly synergistic) benefits of interferon could not only improve those numbers, but should happen even faster. I can't wait to see that data in a few months. I have to be careful with my expectations though, but then again, the first results were quite dramtic. I don't know if I mentioned this before, but the lead scientist for BILN 2061 is now employed by them, and has been pushing this drug vigorously the last couple of years. He may not have developed it, but he has been pushing it.

[couldn't think of a nickname]

This phase IB will last 2 weeks only, and is not designed to measure SVR. It's design is to show the additive effects of interferon to VX-950.

Phase II will start by the end of the year, and will be a 1 month study of interferon and 950. A 3 month follow up will be used to measure SVR.
They will do a 3 month study of 950 alone starting early next year, and will also have a 3 month follow up, with SVR being an endpoint. They may do other trials as well, but those are the 2 most being discussed by them. Data will come out from these trials as early as early 1st qtr. of 2006, and then on down the line.
Phase III is scheduled for 2007, and they feel the FDA will require a 6 month follow up for these studies. It is ashame since the new, sensitive Taq Man Assay has shown that undetectable at 3 months is the same result as being undetectable at 6 months with the less sensitive tests.

An NDA is planned for 2008 (hopefully early). An NDA is a New Drug Application. The FDA normally rules on these within 12 months. This, however, is a lock to be given what is called a priority review. In that case, review time is within 6 months.
It would probably be late 2008 for drug launch if the timeline goes according to plan. It is an aggressive timeline, but so far, they are at, or ahead of schedule. They have started producing manufacturing batches, etc.

I have followed this since it was just a compound in a lab going back almost 5 years, which is hard to believe I have followed it that long already, which means, more than half of the time to approval has already passed.

When I first heard about this (from my involvement in the stock market) they talked about this compound that in replicon assays eliminated the virus in 14 days with no rebound. The hurdle was seeing what it did in people. The first hurdle is often the toughest for these, and it cleared it easily. Side effects were very minimal, and the drug has been well-tolerated. It was about a year ago (almost exactly) that they first tested it in healthy volunteers. I have learned a lot (and still learn) by following these developments. I have learned a great deal just by listening to their conference calls. They archive some of them, so you can check them out, and their prior press releases.

[v eggie dip]

this is the only forum I have seen the time line of 950 being so aggresive (aggressive), I sure hope you're right..I am waiting for that drug....Other forums say 10 years to have anything available other than interferon/riba...I can't wait 10 years and am taking a gamble on Vertex....

[NYgirl]

If we all chip in perhaps we can start our bubble boy commune somewhere in Europe eventually and get in on this if the States don't get their act together.  ;-)

Just kidding.  This is just such huge news.

You know I think if they tested everyone in the good old USA and found out what the REAL number of people with HCV are...they would somehow get their butts in gear and find some serious funding and we'd have a cure in no time.

[couldn't think of a nickname]

The information I give is public record, stated by the company, and the many analysts who follow the company. So far, their timelines have been true. 10 years was fine to say 6 years ago. My reg. doc a couple of years ago told me 3-5 years, and he didn't know about 950 at the time. He has talked to many of the leading hepatologists in the field, however, including Dr. Schiff. I don't know who is saying what in other forums, but it sounds like they don't follow this particular drug, or haven't done any research on it. I will paraphrase VRTX from their conference call yesterday, when they said the timeline is very aggressive, but doable, and they are at, or in some cases, slightly ahead of schedule. For example, they have an RA drug in Phase II (VX-702, which is promising) that they announced all year should finish enrollment at the end of the year, and it is already enrolled. Hopefully the same thing happens with 950.

[couldn't think of a nickname]

I forgot to add that they also stated that the improvement in LFT's was faster than seen with any current drug, or drug in development. Basically, inflamation (inflammation) was substantially reduced very rapidly.

[v eggie dip]

you had a conference call with a drug company?  are you in media or a investor?

[v eggie dip]

New HCV Drug BLX-883, a form of alfa-interferon:
Biolex Therapeutics Successfully Completes Phase 1 Study for First LEX System (TM) Produced Therapeutic Protein

[couldn't think of a nickname]

no, I listened it. It is open to everyone (always) and archived on the site. Only anlaysts (I think) got to ask questions.

[cougareyes]

I know everyone is so desperately hoping for the magic bullet. So far everything I understand the vx-950 and others are bringing down the viral load faster, that it's. We are a long way to see if these new drugs can provide SVR.
They were excited about interferon reducing vl and then as time went by they saw the relapse rate. Then they added riba and the SVR rates inproved. Now they also raised the dosage and recommend not lowering riba dosage. But before they found that out countless people used interferon mono therapy, lower rba dosages, shorter tx duration and RELAPSED.
So far these new drugs seem to be more of a replacement for interferon, it would be great if these can be used alone; but I fear we have a long way to go. Once the vl is undetectable in a blood test will there still be a need for a scavenger drug(like riba). If not how many people will relapse to find the right combo and duration of tx.
I personnally am not the guinea pig type so for me there is alot more data that needs to be processed before I can get too excited. It will happen but in whose time, if you are banking on it be careful of how much time you really believe you can wait.    Peace

[cougareyes]

We are getting alot of undetectable readings w/combo right now at the 4 week mark. Most still don't even get tested until 12-wk. I've heard some report undetectable at 2-3 weeks. If the 4 wk pcr became norm, I wonder what the #s would be.
Back to 950 and others, we are also hoping for less sides, let's pray. SX may not show up until on a full blown tx protocol. Peace

[Forseegood]

Hi, like I mentioned, I have a very small email relationship with one of the biologists that invented this drug, and he's still in on it as a consultant from what I understand, but I feel I'm too overworked and blasted to really ask the questions I'd like, is it all possible that you can email me or I you so you can ask these questions of him? I thought we might wait till there are more findings, but why not soon? We could three way call the guy, whatever. If youre open to it, if not, that's fine too. I just don't know how I'd get in touch with other members here if we are not allowed to post email addresses. Maybe someone else can help on that.

Also, there is the phenomenon of secret trials right? Where they don't advertise to the public at large. This went on with many different drug trials, and the participants were made to sign non-disclosure agreements.

Also, for the skeptics at large, it's healthy to have some sketicism, but this drug works differently then riba in that it doesn't explode red blood cells and more to the point "inhibits" replication from what I understand. (If I'm wrong, I stand corrected.) I'd be more freaked out about Riba then this stuff. I remember years ago when the peg introns came out, people were skeptical about them as well when they were in trials. Everyone I talk to "in the know" is excited about these drugs.  And if they prove to be as good as people are thinking they are from preliminary findings, lots of good things can happen. From what I understand they do not act like the protease inhibitors for HIV. It's a whole different approach.

A drug that proved to be really great to deal with a different disease, for the life of me I can't think of it right now..was fast tracked within two years, when they expected four. I guess it has to be a perfect storm of circumstances.

Also CTOAN, since you are such an inquiring mind (and we all thank you soooo much for it I'm sure) do you know much about those experiments with different diagnosing procedures (one involved dna, and/or proteins?, to calculate who would be a good candidate for the peg introns and who wouldn't? Don't mean to load on to your burden, just asking if you are anyone does. Thanks!!!!!!!

[dammitjanet]

Once again, thanks for keeping us informed on developments with VX950.  I imagine we will be hearing even more after the conference in San Francisco next month.  I see that Vertex is presenting there, so our doctors should be more informed, and that would be a very good thing.  I listened to one of the archived conference calls recently and it sounds very encouraging so far.  Of course, I'm no scientist (nor have I ever played one on TV and I haven't stayed in a Holiday Inn Express recently).  Skepticism is healthy; so is hope.  Thanks again for keeping us in the loop.  DJ

[cuteus]

it is refreshing to see another reality checker and cautious skeptic...
no need to add anything to the cat's eyes

[Snookmiester]

I was told that the PhaseII trials for VX-950 would be taking place here in the South Florida area as soon as a month or two.
If anybody in South Florida wants to look into trials, link up with me and I can supply contact info.
They are also running trials for a vaccine, but that trial is still in the early stages, phase I, I believe.

What I've heard about is sounds VERY, promising..

[v eggie dip]

I talk to a guy online that is in the albuferon study here in Canada..He said he has no sides at all. there is no riba in it!  He cleared right away too...But I don't know how long he will be on it, forgot to ask him that, will in next email I send..

[cuteus]

the goal is to achieve SVR, not just kill virus quickly. A good number of EVRs still relapse, wasn't revenire one of them?
Let's see the SVR rates for ones, then I am a believer.

[couldn't think of a nickname]

I am not sure what your friend (who is an awesome source) can really tell us outside of the what is public knowledge. There are so many restrictions now on disclosures, it would open up a can of worms even if I could think of anything to ask. I thank you for the offer, but I think I am like others, just waiting for more data.
VRTX being a small biotech seems to let the marketplace know about everything relevant, so I don't think there will be secret trials. Do they exist elsewhere? I don't know.

You are correct about the action of the drug. It targets the NS 3/4 protease which is only found in the virus, not in healthy human cells. Some have speculated that fewer sides would be expected with that technology. The drug uncoats the protein of the virus so it can be identified by our immune system as a foreign invader, and our immune system "eats" it. I would imagine swollen glands should be expected. Since the half life of the drug is about equal to the half life of the virus, the drug doesn't wear off prematurely. I think the half life issue has always been an important one.

I have heard of what you mention in your last paragraph, unfortunately, my knowledge of that is pretty much nil. I wouldn't be surprised if that is the way of the future, as others have expressed that as a possibility, I think including our new acting FDA chief. It makes sense, since no two are totally alike, including identical twins.

Janet, that conference should be interesting. I have printed out and read all of the relevant abstracts for that drug and also Schering's. Schering plans their trials to last 24 to 48 weeks as their 2 week vl reduction was much less than VRTX's, but still much better than current therapy. I think the number was a mean drop of 2.07 logs, but don't quote me on that. That drug also targets the same NS 3/4 protease.
I think Pru held a call based on those abstracts for both today, but I have no idea what was said. You needed to be a customer to listen in.
Also, there are other interesting abstracts on that site-like PM protein being beneficial for cirhottic patients (which I think the opposite is done), and studies on various herbal combinations that showed vl reduction and improvement in inflamation (inflammation) numbers, and also on Albuferon as well as many studies on current therapy. The site is pretty much a gold mine of information.

[GoofyDad]

Thanks for keeping us updated. I for one, sure do like the thought of this being in the pipeline rather than not in the pipeline. I know you've got more than a single interest in it. Best wishes!

[couldn't think of a nickname]

thanks goofy, and to you as well.
I am re-listening to the call, and they did say a couple of things that might be worthy of mention.
First, in vitro, interferon combined with 950 prevented the emergence of viral variants (resistance). The key is to show this in people now.
Also, those who achieve undetectable status at the end of 2 weeks, will be rolled over onto the current standard of care. That is good news for them, as they will have a good chance of SVR anyway since the trial is not long enough for SVR, nor is it the endpoint.

TO ALL: I caution, do NOT expect SVR data early next year. That is NOT the goal. This is just to show the combined effects of both together. Phase II is planned to show SVR. No matter what therapy is taken, it is widely accepted by the medical community that treatment needs to be 3-4x as long as it took to go undetectable. If you go undetectable in day 11 of a 14 day trial, we all know that SVR will not occur. It doesn't now in current standard of care.

[Forseegood]

Hey thanks for your thorough analysis - I for one find it really helpful, sometimes when I look at those studies, the words and numbers all start to do a little dance and I can barely suss out anything, unless I read it in the morning. Left brain, right brain, I'd settle for any brain right about now.

As far as talking to the doc, I don't want to bug him about any little thing, so maybe I'll wait till there is more data after this study. One thing he did tell me though, some of this info released is spinned a little for the stock market and stock holders, they don't want to go too crazy with the applause, because then they put too high of an expectation on it...and if one little thing goes wrong, everybody reacts...it's a fine balance they have to walk so they are very cautious about releasing info. But according to him there is every reason to feel optimistic, they have been able to get a beat on why the other protease inhibitors did what they did and they are pretty sure they took out the bugs. Let's hope so.

[couldn't think of a nickname]

cougar, EVR is an excellent indicator of SVR, that is established in the medical community. That is why a minority of people, usually geno 2, that clear in 4 weeks, are treating for a shorter period of time.

It doesn't sound like riba is in the mix here because they stated yesterday that they will only combine 950 with the most potent antiviral out there, and that is still interferon. Maybe in a few years, that is Albuferon instead.

[Healed24]

Good info. Please keep me informed as this sounds promising. Can you direct me to where I can listen in on the call.

Thanks
Brooke

GOD BLESS

[miked]

Great info...keep it coming.  Next month's meeting in San Francisco will tell alot.

Anybody know anything about the Schering SCH503034 trial enlistment criteria?  My doc said that I couldn't participate because I'm considered a "relapser" which doesn't make sense to me.  I got the 2log drop at week 12 and went all the way down to 7,500 copies at week 32....but, at week 36 my VL went up to like 12,000.  Is this a definition for relapser????  

Mike

[couldn't think of a nickname]

The web site www.vrtx.com will have the latest call archived until Nov. 9th I think. They still have the initial call archived from last May. I also think they said they will have another web cast to coincided with their presentations at AASLD.

[cuteus]

I thought a relapser was one who achieved a negative PCR by end of tx, but showed VL 3 months post tx. A non responder is one who shows detectable virus throughtout tx. I guess regardless of whether you get a two log drop, if you still show VL, they switch you to another group label.

It would be great if the new meds targeted substances unique to hcv only, instead of our human cells.  It has to be easier on the body and prevent organ and tissue damage plus possible long term effects.It always bothered me that they have to injure healthy human cells in order to get to the invading organism.

[couldn't think of a nickname]

The new meds in trials do target the virus and not human cells, as per my prior posts. The target is NS 3/4 protease, which is not found in any human cells, only on the virus. This is an example of a small molecule drug. That is why VX-950 has so far shown an excellent side effect profile.

Schering's drug also targets the same protein.

[couldn't think of a nickname]

I have posted there, but I don't post much. Too much garbage.
That is an interesting bit of serendipity. I also am betting 2 ways on this. I have followed the stock since it was in the 90's back in the bubble, but never bought it until last year under 10. A scrolling headline on my stock ticker is how I first found out about 950, and that was probably 5 years ago, and have followed it (and the other compounds) since then.

I sense that maybe a couple in here don't like/agree with my posts on this (oh well), but I post mostly facts and very little opinion on this drug as I feel it is our best hope right now. Before I made the decision to buy this stock the way I did, I had to get comfortable with the compound and the company. I think they need to do a better job of Investor Relations at times, but that is a small negative in the overall scheme of things.  
I have to admit that I have considered not posting on any board myself, including this one. I think many in here are aware of it so I probably don't need to continue posting on the subject.

VRTX has an advantage that the current companies that treat never did, and that is 15 years of history. As opposed to the beginning, we know what type of response is needed, and how fast for a chance at success. Dosages are more fine-tuned. Genotype issues are better understood. Cuteus took issue with my statement about EVR. Maybe some do relapse even with EVR. Even so, EVR is still a very relevent stat, and is relevent no matter what compound is used. That is a big reason for optomism because they have shown EVR. The other rule of thumb that helps them is that you treat for 3-4 times longer than it took to go undetectable. That is something else that wasn't known 15 years ago, but is how treatments are designed today.
But, I digress, as this is more venting than a response to your post.

I can't imagine what you went through, but I can guess that on the 24th you were probably pretty upset-totally understandable.
I hope it helped raise your spirits a bit. Maybe you can get in one of their upcoming phase II trials.

I believe VRTX solved the crystalline structure of the virus in the mid 90's. That is part of their technology, and I am reading about it in the book about the company's founding-"Billion Dollar Molecule". The biggest obstacle they had in designed that drug was getting it to "stick to the dimple on the virus".
The great thing about the Forbes article was that it made the expectations high, but they pretty much got it right. I save just about any article I can so I can always go back to them later.
Look for another web cast to coincide with the AASLD meeting.

[mawg]

cthan,

Do you post or just read the VRTX board at Yahoo?

You once mentioned the Forbes article (on VX-950) from January 05.  An interesting bit of serendipity about that article/me/and tx.  That article came out on the 25th.  The IDEAL Study nurse had called me on the 24th and told me I had 'flunked out of school' (only a 1.8log drop at 12 weeks) and I could/should stop treatment.  (I could not have been happier .... I had HUGE sx on tx).

The next day, I came into work (25th) and opened my browser to MyYahoo! and the first article I see is the Forbes article .... "A Magic Bullet for Hep C"  I bought 350 that day .... I've added a bit since then.  I read the science of VX950 (and biology wasn't my major) and the targeting of NS3/4 protease appears to me, to be the correct science.  Their released data and web broadcast seem to this up. Serendipity, indeed.

I tell people that 'I am betting on them (Vertex) 2 ways.'

[couldn't think of a nickname]

Mike, sorry, I can't help you there. SGP has not been forthcoming with any info. I would suggest locating a trial center and contacting them. You might find one by going to www.clinicaltrials.gov . Good luck

[go-girl]

Wold you mind giving me the sites on this info you posted, would like very much to keep up with new meds and trials, thanx in advance, stay healthy

[craigie]

I am very interested in Vertex in addition to Aethlon. Would like to talk to you. Please email me at ***@****