VX-950, Vertex Pharmaceuticals, results of trial 1b

[dharmabum]

Be VERY careful how you interpret this.  Don't make clinical decisions on the basis of this positive result.  Having said that, it is great to know that progress is being made:

CAMBRIDGE, Mass., May 10 /PRNewswire-FirstCall/ -- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX - News) today announced interim results that indicate that the investigational oral hepatitis C virus (HCV) protease inhibitor VX-950 was well-tolerated and demonstrated potent antiviral activity in a Phase Ib clinical trial.
The study enrolled 34 patients with chronic genotype 1 HCV infection who were treated for 14 days with placebo or one of three dose regimens of VX-950. Patients receiving 750 mg of VX-950 every eight hours achieved a median reduction in HCV-RNA of greater than 4 log10, equivalent to a more than 10,000-fold decrease in viral levels, at the end of 14 days of treatment. A median reduction in HCV-RNA of greater than 2 log10 was seen in each of the other two VX-950 dose groups at the end of 14 days of treatment. Every patient receiving VX-950 achieved greater than a 2 log10 reduction in HCV-RNA within the first three days of treatment. Genotype 1 HCV infection is the most difficult strain of HCV to treat and the most prevalent strain in the United States, Western Europe and Japan. Results from the study will be presented by a clinical investigator on May 17, 2005 at Digestive Disease Week® (DDW), a medical conference to be held in Chicago, Illinois. In accordance with the embargo policy of the meeting, the specific data from the trial beyond what is described in this press release will not be disclosed until the DDW presentation.
"Vertex is committed to developing innovative compounds for the treatment of chronic HCV infection. VX-950, one of the most advanced agents in a promising new class of direct antivirals, underscores that commitment," said Joshua Boger, Ph.D., Chairman and Chief Executive Officer of Vertex. "The demonstration of antiviral activity in this early clinical study is highly encouraging, and we look forward to sharing these data in greater detail at DDW next week."
Based on the results of the Phase Ib clinical study, the Company plans to explore the development of VX-950 as monotherapy and in combination with other HCV treatments. Vertex plans to consult with the U.S. FDA and European regulatory authorities on the Company's development plans. Vertex expects to file an investigational new drug (IND) application in the second half of 2005 to support Phase II clinical development of VX-950 in the United States. In collaboration with Vertex, Mitsubishi Pharma Corporation is developing VX-950 in Japan and certain Far East countries.
Trial Design
The Phase Ib clinical trial was a double-blind, randomized placebo- controlled study designed to evaluate the tolerability, pharmacokinetics and effect on viral kinetics of three doses of VX-950 -- 450 mg every 8 hours, 1250 mg every 12 hours, or 750 mg every 8 hours -- over a period of 14 days, with additional post-treatment follow-up. A key goal of the study was to assess different dosing levels and frequencies for VX-950 to provide insight into dose selection for future monotherapy and combination therapy studies. Thirty-four patients with chronic genotype 1 hepatitis C virus infection were enrolled in the study; six patients received placebo and 28 patients received VX-950. The study was conducted at three centers in Europe. The trial included treatment-experienced and treatment-naive HCV-infected patients.
VX-950 Demonstrates Antiviral Activity
Interim Phase Ib clinical trial results indicate that VX-950 was well- tolerated across all three dose groups with no serious adverse events reported, and no treatment discontinuations. Treatment with VX-950 also resulted in significant reductions in plasma HCV-RNA. Within three days of treatment, the median reduction in HCV-RNA was greater than 3 log10 in all three VX-950 dose groups. In the dose group receiving 750 mg of VX-950 every 8 hours, there was a further reduction in viral levels between days 3 and 14 of treatment, with mean and median HCV-RNA reductions of greater than 4 log10 at day 14. Trough plasma concentrations of VX-950 were highest in the 750 mg every 8 hour dose group. In the 450 mg q8h and 1250 mg q12h dose groups, maximal effects were seen between days 3 and 7 of treatment. Subsequently, there was an increase of approximately 1 log10 in median HCV-RNA between days 7 and 14 evident in both groups. Full analysis of the study, including a detailed pharmacokinetic and viral sequencing evaluation, is underway.
Web Cast Conference Call on May 17
Following the presentation of VX-950 clinical data at DDW, Vertex Pharmaceuticals will host a conference call on May 17, 2005 at 4:00 p.m. Eastern Daylight Time (EDT). This call will be broadcast live via the Internet at http://www.vrtx.com in the investor center until end of day on May 30, 2005. Alternatively, to listen to the call live on the telephone, dial [phone] (U.S. and Canada) or [phone] (International). The archived call will be available via telephone commencing May 17, 2005 at 8:00 p.m. EDT through 5:00 p.m. EDT on May 23, 2005. The replay phone number for the U.S. and Canada is [phone]. The international replay number is [phone]. The conference ID number is 6231209 for both numbers.
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is principally focused on viral diseases, inflammation, autoimmune diseases and cancer. Vertex co-promotes the HIV protease inhibitor, Lexiva®, with GlaxoSmithKline.

[dharmabum]

Unbelievable!!  These results are really remarkable.  Don't avoid this post just because it is long and somewhat complicated.  This is the most important news yet.

Of course, read the news with a healthy dose of skeptism also.  Who knows where this drug will be two years from now, but given the current profile of the FDA, this drug will probably receive either a "priority review," a "fast track designation" or "accelerated approval."

As I said in the earlier post, don't make clinical decisions based upon these results, but watch the development of this drug carefully.  It is interesting from a scientific standpoint and encouraging from a patient perspective.

[mikeymike2]

thanks for posting this dharmabum - very interesting and worth watching

[cigaso]

My main question is has anyone in any of the groups attained SVR? Maybe I read it wrong, but I didn't see it. Maybe it's too early to tell. However, the 2-4(10) log drops in such a short time is incredible. Also, the fact no one dropped out is significant. This is worth watching. Thanks for posting.

[Califia]

Figured you might appreciate that.   It's certainly more substantial than the imaginary chocolate I offered in the thread below.

[snook_man]

"cure"... Please!! Do not get your hopes up on phase I trial results.. Do we all remember the last protease "Cure"? It was the next thing, even got further in trials, till it showed heart toxitity, and was thrown in the garbage.. BILN 2061?

What I do not see anywhere in this posting is whether or not a SVR was obtained. If SVR is not obtained, what signifigance is the VL drop? Many of us obtain undetectable statis, yet relapse. Many go months of NO VL at all, yet do not obtain a SVR..And the time frame in which these patients where monitored is minute. I won't get my hopes up till I see some LONGTERM results, LARGER numbers of patients, and the word SVR mentioned in the conclusion..

[Califia]

Thanks for posting this.   The amount of drug development activity taking place right now is truly encouraging.   But of course these are Phase I results, and there is no mention of the toxicity profile.  I've definitely heard of infergen achieving comparable VL reductions  within the same period of time, but it's reputed to be a very rough ride.

Btw,  I think it's safe to assume that most people posting or lurking here remember all the discussion that took place a few months back about  the persistence of virions after SVR.   But it's an important reminder nonetheless.  Welcome to the list, by the way!

[mawg]

cigaso,

I have been watching Vertex since an article appeared on my Yahoo page (via Forbes) on 25 Jan 2005.  If you like annotate coincidence I was called on 24 Jan 2005 and told that I had 'flunked out of school' on the IDEAL study for my 12 wek VL test.  I only had a 1.8log10 drop in my VL and the study required 2log10 drop at 12 weeks.  I could not have be happier, than to be told that I did not have to take my shot that night--I suffered a lot of sx from tx (and they seemed to be increasing).  

So, the next morning, I show up at work (I think I was there) start up my browser and here is a news item on Vertex VX-950.  Fate?  Ying and Yang? Devine intervention--I don't know.  But it was a 'sign' of some kind--that I know.

I have listened to their webcast/presentations that VRTX has made at several financial conferences.  One of the webcast had the powerpoint slides included.

The most interesting slide depicted an Invitro (sp?) testing of HCV, HCV vs Inf/RBA, and HCV vs VX-950 over a 30 day period.

The most important information was the 14-day point.  HCV was constant across the 30 days.  Inf/RBA vs HCV showed a  2log10 drop in viral load (VL) at the 14 day point, but then it climbed back to steady state.

VX-950 vs HCV showed a continous decline in VL--down to 0 at the 14 day point and then flat-lined (at 0) through the 30 day point.

Vertex is going to present a 'formal' finding of their data on May 17 at the Digestive Disease Week (DDW) conference.  Since their trial data is following their experiment data I (me, no one else, only my opinion, a stupid aviator) expect for them to announce that the 30 day data is--in my very uninformed, non-scientific, non-medical, non-professional, only-hoping, opinion--complete SVR  (I'll even say the 'word'--Cure).

mawg

[BronxRican007]

I for one appreciate any news on the HCV front. I'm eagarly waiting for more news on VX-950. GO BIOTECH!

[cigaso]

Mawg,

Thanks for your response. For yours, maybe mine and everyone elses sake who has HCV, I hope this is the magic bullet we seek. I am intrigued by the potential of this treatment. It is worth watching, but it will be a while before it's ready for the masses.

Snook man,
You asked the same question as I did and brought up some good points. Until there is documentation of SVR over a period of time, we shouldn't get too excited yet.

[bluepeng]

I realize VX-950 is targeted for genotype 1b in these trials, does this mean it's not targeted for other genotypes?

[snook_man]

I'm doing fine.. Hangin in there to say the least. Seems like the tx switches gears at the week 24 point, and you just gotta hold on!! Just starting to lose some weight. Dropped from 176lbs to 162lbs. Wife is dieting to keep up.

Yep, my VL was only 4000 going into tx. For more than two years I was told that I did NOT have HCV anymore, and must have fought it off. Initial Dr visit last year, VL was 5463.. I was told it was a mistake. And yes, moderate liver damage.
We have all been around long enough to know that VL does not effect liver damage. All that matters with this disease is SVR!!
What I have found on the net and by asking Dr's their opinion about my condition, is that I have a VERY strong immune system. My body was fighting extremly hard to keep the virus at bay, at the same time actually speeding up the fibrosis progression.

LMAO... Hmm, that picture was Snook_man just doing what he does.. That was a 20lb snook caught on the SW cape of Florida.
Hope all is well with you, and you are enjoying your new life HCV free! I'll be joining you soon!

[Califia]

The debate on this list and many other HCV boards about the correctness of deferring treatment  seems to mirror the range of opinions within the medical community itself.  Here's a link to a 2002 presentation by Robert Gish, M.D., who argues for selective treatment until less toxic and more effective therapy comes along:

<a href=http://www.medscape.com/viewarticle/443005_7><b>HCV - The Case for Selective Treatment</b></a>

[miked]

Guys, this really is good news.  

However....a Phase 1B clinical trial is to prove the efficacy and toxicity of a drug in a very small, controlled group of patients (30 or less).  If successful the Phase II trial will treat a greater patient population but with the same goals for efficacy and toxixity.  Phase III is when it becomes real and involves many (thousands) of patients.  Pase IV is basically pre-production and release of the drug.

We should all be encouraged but don't view this as the cure, yet.  NM283 is another worth watching as well.

[Tallblonde]

Thank you for the information from the Gish presentation.  I particularly liked this statement:

"But the patient with minimal fibrosis, how can you help them? I think those patients are best deferred until treatment improvements take place in the future."

It's good to get some validation from someone with his credentials.

Susan

[Tallblonde]

Another presenter at the same session, Dr. Douglas R. LaBrecque, had this to say:


"I began by saying that virtually all patients should be treated for chronic HCV. Obviously, there are some patients where you may consider deferring or not using therapy at all. Patients who have a long duration of disease with minimal evidence of damage on biopsy, particularly those with genotype 1, may wish to defer treatment until a more effective therapy for genotype 1 is available or one with fewer side effects. Older patients who have minimal disease, particularly those with major medical problems, are also good candidates for deferral of therapy. However, whenever one chooses to defer therapy, follow-up periodic liver biopsies are required and this must be taken into consideration and discussed with the patient as well."

[cuteus]

It just gets to me that these practitioners never mention anything else but cirrhosis as the marker for treating. never extrahepatic symptoms, that so many suffer, even at stage 1.

[Califia]

It's funny, because one-to-one Gish is the most knowledgeable and sensitive doc I have ever known when it comes to the extra-hepatic.   But remember the whole profession has been focused on life-threatening liver damage--heck, they're liver specialists.   But when Gish actually recommends tx, it is aggressive treatment.  He's just fully aware of the possible downsides, that's all.  With me, he noted that I was reentering tx for reasons of "QOL."   My fibrosis has been stable for so long that no one was really worried about progression (rightly or wrongly).

It's all about  juggling risk and benefit.  If I were a doc, I would definitely have a hard time accepting the fact that I might well increase the suffering of  some percentage of my patients with the medications I prescribe.

[BronxRican007]

Funny a couple of you mention extrahepatic symptoms. My mil docs ignored and never tested me for hepatitis. For years I had right side abdominal pains, lichen planus, colds that lingered for weeks, and coughs so bad I would pass out. No one ever suspected HCV. I was told nonsense like, "it's a cold, you'll get over it" or "looks like you pulled a diaphragm muscle", and "it's lichen planus...here's some cream". I wish I had someone like Dr Gish earlier. By the way ...who the hell is Dr Gish?

[Califia]

He's a fine hard working hepatologist who runs the Liver Transplant  Center at Pacific Medical Center in San Francisco.   No relation to Lillian Gish, I don't think...

[BronxRican007]

Thanks for the info. Too bad for me I'm on the east coast and stuck with mil doc bozos. I have a Gastro appt this month. If the doc turns bozo on me..I'll seek civilian care. It's my health, I got to do the right thing.

[Califia]

With the full force of this crazy forum behind you, that poor VA doc isn't going to know what hit him.   You are going to go in there armed with so many questions he'll think you've been buried in medical books for the last few years.  As for civilian care in NYC, if it comes to that, stick close to your homie Cuteus.   (I know how far it  is from the Bronx to LI, but you know what I mean.)  The woman definitely knows what she's doing and will no doubt steer you right..   Btw, sorry to meet you under these circumstances, but it's a pleasure nonetheless.   Welcome overboard!