Vertex Pharmaceuticals Announces Start of Phase II Clinical Development for Inve

CAMBRIDGE, Mass., Dec. 5 /PRNewswire-FirstCall/ -- Vertex Pharmaceuticals Incorporated VRTX announced today the initiation of a Phase II clinical trial for VX-950, an investigational oral hepatitis C virus (HCV) protease inhibitor for the treatment of HCV infection. The 28-day study will evaluate the safety, tolerability and pharmacodynamics of VX-950 when combined with pegylated interferon and ribavirin. Pegylated interferon and ribavirin are two approved treatments for HCV infection. Twelve treatment-naive subjects will be enrolled in the study at two centers in the United States. This is the first clinical study of VX-950 to be initiated under an open investigational new drug (IND) application with the United States Food and Drug Administration, and marks the beginning of a broad Phase II clinical development program planned for VX-950 that will evaluate the compound in multiple clinical studies in 2006, including a three-month study in more than 200 treatment-naive patients.

"This first Phase II study for VX-950 will enable Vertex to evaluate the safety, tolerability and pharmacodynamics of VX-950 over 28 days when combined with pegylated interferon and ribavirin," said John Alam, M.D., Senior Vice President of Drug Evaluation and Approval at Vertex. "This initial Phase II trial is anticipated to support the evaluation of VX-950 in a key three-month Phase II study in more than 200 HCV patients that we expect to initiate in early 2006."

[scruffy]

That is UPBEAT and hopeful news. thankyou.

[beamishboy]

wow!!-so soon..&their doin combo w both interferon&ribivarin-thnks for the heads up!!LIght at the End of Our Tunnels!!!!

[couldn't think of a nickname]

I wouldn't read too much into the riba part. This trial is very small, and they have still been saying they will do other arms in future trials without it. This may have been required by the FDA.
It is highly illogical to think that riba will be a must with that treatment. It did better in 2 weeks alone than current SOC could do in 12 weeks. I think the only one who wants to see riba stay in the treatment are the makers of it.

[couldn't think of a nickname]

I would also note that the current phase 1b is combo with interferon and 950. I don't believe there is any riba arm in it. The company also stated in a web cast last month that they only wanted 950 paired with the most potent antiviral, and that was interferon. They also stated they didn't want something that wasn't as good to affect the side effect profile, meaning, the biggest impact riba would have, would be there would be riba sides.

In the 1b trial that is ongoing, I believe the sides will be interferon related, as 950 was very well-tolerated by itself. Those in the triple combo shouldn't have much additional side effect problems.

Having said all of that, this is NOT a surprise, as we knew it woould be tested in combo, and we knew that there would be riba ARMS. That was stated in recent web casts.

In fact, I think in the broader phase 2 that is upcoming, they have said there would be a mono arm, an interferon arm, a combo arm, and a riba arm (I think 6 in total). Not at all unusual for phase 2, as what works best will be focused on phase 3 for fine tuning.
I will say this though. I don't care if the approved combination is for 950 plus interferon and riba, I will not take riba. It works without it.

[vegas777]

"I will say this though. I don't care if the approved combination is for 950 plus interferon and riba, I will not take riba. It works without it."

Hi there, haven't seen you in awhile..Hope you are doing well...I agree with you 100% with the upper comment you made...I will not take riba either...And why would Vertex even consider using the riba in their "end product"...They would loose out on the huge market of people like you and I that are waiting and watching, so I rather doubt this is in their long term goal for 950...

Like coug says :just one man's (in my case woman's) opinion - Peace

[vegas777]

everyone makes their own choices in health and in life, one does not make the other right or wrong, just their's

[couldn't think of a nickname]

I am hanging in there, hope you (and everyone) are well.

Just my opinion, but I think the riba decision is likely from the FDA. They have always talked about changing the treatment paradigm to monotherapy.

I will also offer this opinion, and this is strictly my opinion, based on following this particular compound for a number of years. I think they were very smart in doing the first phase 1b alone. The best in vitro results came very close to what they saw in the TID group, so the in vivo numbers came in strong at 4.4 logs in 2 weeks. Once that gets out there, it says (to me anyway) that this drug can be tremendously more potent than SOC, which should raise doubts whether current SOC will be part of the future. If the data came out weaker, then it would have been a tough sell to say it could work alone. At the very least, interferon and 950 should be sufficient. I think the current 1b trial will show even better results, we should know in weeks to maybe a couple of months.

Here is another consideration. We don't have kids yet, and we would like to. I am getting late in my 30's, my wife is a few years younger, but I want to have a cure out there for me (or at least see one close). What would riba do to any future children? Is waiting 6 months enough? I would not want to take that chance with my future children's health if I don't have to. With all apologies to those who have attained SVR with riba and how it has helped, I have too many concerns that I am not comfortable with if I don't need it.

Since I am letting opinions fly (what the hell was in my breakfast this morning?) I have re-thought participation in clinical trials. Maybe the ACV has me feeling a little better and it might affect a decision, maybe not. But, if I had a choice of being in a phase 2 or phase 3 trial, I think I would rather be in phase 3. That should offer the best chance for SVR as they would (according to plan of course) be fine-tuning from phase 2.
Having said that, those in this current trial will be offered SOC after the trial is done, and I think that is great that they offer that.

[vegas777]

I would jump on a phase 3 trial as well, if I could

[couldn't think of a nickname]

After what happened with BILN, there is extra skepticism, and with reason. He is right that the fastest path to market is with existing drugs, but I think that if the non-riba arms get SVR, it won't need that for approval. One thing that we need to keep in mind is, that the FDA needs to see safety and efficacy for approval. Unlike Europe, it does NOT have to be compared to SOC. I just hope the FDA is not unreasonable, and understands how badly these newer therapies are needed. I think with drugs that offer much hope, are seen as guilty until proven innocent, because otherwise, it could be problematic for many reasons. In 2003, when they put out a press release saying that a particular in vitro study showed a 4 log drop in 9 days, with clearance in 14 days, many said, "that's great, but will it work in people, and how about the sides?". Both good questions, but they came close to duplicating that when many thought they might not get this far. Hopefully, that same positive course continues, so one day, we can all be on here and say "remember when we had that stupid bug?"

With 3a, maybe he did feel your chances of clearance were high, so he wouldn't advise waiting.

[NYgirl]

I just read this at cnn.com  I don't know if I should post the link or the article so I'll post excerpts and you can go to cnn to read it or tell me how is the right way!

WASHINGTON (Reuters) -- Coffee and tea may reduce the risk of serious liver damage in people who drink alcohol too much, are overweight, or have too much iron in the blood, researchers reported on Sunday.

The study of nearly 10,000 people showed that those who drank more than two cups of coffee or tea per day developed chronic liver disease at half the rate of those who drank less than one cup each day.


The study, conducted by the National Institute of Diabetes and Digestive and Kidney Diseases and Social & Scientific Systems, Inc., found that coffee provided no protection to people at risk of liver disease from other causes, such as viral infections.

[vegas777]

Hey Debby :)

I asked my Naturpathic Doc about coffee and all the press it is getting for "being liver freindly" and she said hogwash!  hehehe  just her opinion...she's entitled...I drink 2 cups of coffe most days, but not because it is or is not "liver freindly" ...I drink it cuz it tastes soooooooooooooo good :)

Have a wonderful day Miss New York!!

*dippa dee doo dah*

[vegas777]

Hey Debby :)

I asked my Naturpathic Doc about coffee and all the press it is getting for "being liver freindly" and she said hogwash!  hehehe  just her opinion...she's entitled...I drink 2 cups of coffe most days, but not because it is or is not "liver freindly" ...I drink it cuz it tastes soooooooooooooo good :)

Have a wonderful day Miss New York!!

*dippa dee doo dah*

[NYgirl]

Throwing a pie at ya...might taste a bit better.  A bit of ice cream on top too!  ;-p

(*Still waiting for the picture though!*)

[couldn't think of a nickname]

The next trial will have non-responders. I think it is better there aren't any, as this trial is too small to make any good conclusions.
As for me, there is also the thalassemia minor matter as well.

If interferon adds 1 log to the decline, like it has with other drugs in trial, an average reduction of over 5 logs in 2 weeks would be major. As good as things went in the first trial, there are new questions that have arisen from that trial, maybe in a good sense.
First, the tablet form is supposed to be better than the oral suspension used.
Second, it is 2-3 times more active when taken with food. In the first trial, it was taken on an empty stomach.
Third, we haven't seen how much interferon will add.
We do have to have these answered, regardless of whether it looks better or not.

I have resisted saying this, but I might be the only one here that wasn't shocked by the results, even though the company said they were surprised. Maybe I am naive, (and I do know better, believe me), but I have known for over 2 years that an in vitro study dropped the vl over 4 logs in 9 days, and it killed it in vitro with no rebound. Obviously, a body is different than a test tube, but they came close to reproducing that in vitro study in vivo. So, I might have had the highest expectations than anyone else, and they were basically met or maybe exceeded. Maybe that is why I still have high expectations. We will never know what their expectations are/were. You have to be careful not to over-promise when you are a publicly traded company, and one would always prefer a good surprise over a bad one. I would love to be a fly on the wall though.

[vegas777]

fingers are faster than brain these days...lol

one more thing though - I drink warm water half half a lemon squeezed in it everyday - this helps with inflammation

[NYgirl]

Uh dear friend maybe you better CUT DOWN on the coffee??? hahahahahhaahhahha

I drink about two cups a day myself LOL.....

[NYgirl]

Dippy

Why warm water with lemon?  Not cold?

Such a coffee fanatic brain fogger I forgot to type that out too before I hit send!

Dizzy

[GoofyDad]

"This initial Phase II trial is anticipated to support the evaluation of VX-950 in a key three-month Phase II study in more than 200 HCV patients"

As I read it, this is a required stepping stone for the 6-arm trial. Looks like it goes like this:

* Evaluate safety of VX-950 and establish optimum dosing (complete)
* Evaluate safety of VX-950 in conjunction with approved  treatments (28 day trial)
* Compare efficiacy of VX-950 against, and in combo with, approved treatments (six arm trial)

The end result could indicate any of several possible therapies - mono, combo, whatever

[vegas777]

Not sure why it has to be warm, that's what my Naturpathic Doc said to do

[GoofyDad]

Cold water reacting with citrus can reverse the polarity of the Cha meridians causing fluctuations in the vital flow of life-force. Wearing magnets in your shoes can help, but use caution if you're unsure of Iron levels.

Throw tomatoes this way.....

[vegas777]

throwing maters at ya!  lol

[GoofyDad]

Hi Kalio - Always nice to hear from you. 12 week VL will be drawn Thurs. I was clear at week-4, so hopefully this should be a non-event (knock-wood.... OUCH!).

Did you post the results of your 12 week, or am I brain dead? Either way, best wishes to you - I hope you have the best of news to share with us.

Seems there are a number of us 3a's posting these days.

Now where's that peacock feather?

[mawg]

My guess on this trial: VRTX is going to see if they can get a '30-day kill' on the virus.  If they get SVR with this combo, in 30 days, the sx from IFN/RBN are minimal (not withstanding your concerns about RBN caused birth defects).  

I didn't start to go downhill until about 60-70 days on tx.  If they get SVR in a month, using 'all the big guns', I'd be willing to do the IFN/RBN again.  Then perhaps 950 mono for 60 more days-just to make sure.  

I wish they would have tried this arm with non-responders, too.  But only so much time (and investor money--part of it, mine) is avialable.

mawg

[vegas777]

I ran out of maters so I switched to lemons!!  lol

[cuteus]

it seems to me they have to iron out the matter of the viral rebound on the subjects given  a certain dosage of the med. Given the individuality in human reaction to dosages, which one is going to be the best for the average person and which for the resistant individual?  Even though none of the subjects in the higher doses(?) got a rebound, when more people are added perhaps that same dosage won't be enough for some resistant strains. This is the one item I find most disturbing, a viral rebound while still on the meds.

[couldn't think of a nickname]

That question was answered in the viral kinetics data. There were 3 groups: rebound, plateau, and continual decline, and each one was defined by the trough concentration level, which is the MINIMUM amount of drug still measured in between doses.
In the rebound group, the trough concentration level (TC) was 719 nanograms per mililiter.
In the plateau group, it was about 850 nanograms per mililiter.
In the contitinual decline group, it was 1050 nanograms per mililiter.
What that shows is, that those who maintained optimal trough concentration level, saw no rebound, and the greatest declines in vl.

That data helps, in that now they know what TC level should be targeted in the body, and can make dosage adjustments, etc., based on that.
It also seems to be common sense that those with the highest amount of drug in the body would see the best effect.

In the future trials, they are not using the doses that led to sub-optimal TC levels.

I would also like to note that the data compiled was extremely extensive for a phase 1 trial IMO. They may have gotten lucky in that they were able to identify these key levels and find a good dose for phase 2. Apparently, SGP did not have the same luck, unless it is just that the drug isn't as potent. Phase 1 is normally for safety, and an early peek at viral kinetics.

[couldn't think of a nickname]

I should also point out, and maybe sometimes we forget, that data was based on a single novel drug. In vitro, interferon adds to that, and it did with SGP's also.

I think we are all looking for a silver bullet, but here is some more perspective.

In 2 weeks, at TID, they have half go below the limit of quantitation. Current therapy does that in 12 weeks (maybe more, these were all geno 1's), and is considered the gold standard. The current gold standard has also shown rebound in some, but it is still the gold standard.

If VRTX had done that study, and never published reports on it, and then did another with ONLY TID dosing, it would have looked like gold. Fact is, they experimented with 3 different doses, and even though those doses far exceeded what current therapy does in a short time frame, they did not work optimally, so they will not be used in the next ones. That's what phase 1 is for.

As for SGP, it looks like they might have to go back and do another phase 1b to find a better dose, as their data and decline slopes were not as good as one would like. They actually had a rebound in between the 2 decline slopes, which looked odd to me.

[couldn't think of a nickname]

http://www.fda.gov/cder/handbook/accel.htm
This describes the accelerated review process.

http://www.fda.gov/cder/handbook/preclin.htm
preclinical

http://www.fda.gov/cder/handbook/phase1.htm
Phase 1

http://www.fda.gov/cder/handbook/phase2.htm
phase 2

http://www.fda.gov/cder/handbook/phase3.htm
phase 3

http://www.fda.gov/cder/handbook/indbox.htm
Investigational New Drug Apps.

http://www.fda.gov/cder/handbook/treatind.htm
Treatment IND

http://www.fda.gov/cder/reports/reviewtimes/default.htm
drug review timelines

on the www.fda.gov web site, there is also a link for petitioning the FDA. I don't know anything about that though.