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creation301
05-04-2012, 01:35 AM
I know this has been discussed before, but can't find the link. Are there any DDf508's on Kalydeco? In clinic the other day our Dr. said he thought it was worth a try for every DD due to the small subset that responded well in the study. He even went as far as to ask if we would like to be that experiment at our clinic?
My first resoponse was of course, but then in reading other post and articles, I am not so sure, as it may be a really, really long shot. First, we would have to actually get it approved through insurance. Which would be a HUGE if, I am guessing.
It's not going to harm our daughter, so the worst case is that it would do nothing. Right? My one caution is that she is only 6 (almost 7) and would not be able to articulate the differences if any in her body.
We love research and are very open to her being in trials when it is wise and she is able. The sodium cloride levels would be non-subjective, along with her pft's which is tempting. Just hard to think that no other information would most likely be gleaned.
Anyway, just curious if there are any opinions out there that might be helpful.
Also, if there are any other bits of information to help with insurance, I would love you to PM me.

Thank you in advance for your help.

creation301
05-04-2012, 01:35 AM
I know this has been discussed before, but can't find the link. Are there any DDf508's on Kalydeco? In clinic the other day our Dr. said he thought it was worth a try for every DD due to the small subset that responded well in the study. He even went as far as to ask if we would like to be that experiment at our clinic?
My first resoponse was of course, but then in reading other post and articles, I am not so sure, as it may be a really, really long shot. First, we would have to actually get it approved through insurance. Which would be a HUGE if, I am guessing.
It's not going to harm our daughter, so the worst case is that it would do nothing. Right? My one caution is that she is only 6 (almost 7) and would not be able to articulate the differences if any in her body.
We love research and are very open to her being in trials when it is wise and she is able. The sodium cloride levels would be non-subjective, along with her pft's which is tempting. Just hard to think that no other information would most likely be gleaned.
Anyway, just curious if there are any opinions out there that might be helpful.
Also, if there are any other bits of information to help with insurance, I would love you to PM me.

Thank you in advance for your help.

musclemania70
05-04-2012, 08:20 AM
DDF508 did not respond to Kalydeco for the most part. Yes, there were a few individuals who may have had decreased sweat chloride, but the change in sweat chloride was NOT SUSTAINED through week 40 of the trial. Neither were the gains in fev1.

I'm not saying don't try it, but don't be surprised if your insurance says no. Studies showed that DDF508's had no where near the improvements that g551d had and they will use this to deny coverage.

If you have the time, energy, resources and stamina to fight the system, I encourage you to try. Please keep us updated.

I can send you the chest article in PDF that shows the results of the trial specifically for DDF508s if you want to pm me your email address. This may help you to make a better decision. I had a personal meeting with a Dr. on this study and I may be able to help answer your questions if you have any.

musclemania70
05-04-2012, 08:20 AM
DDF508 did not respond to Kalydeco for the most part. Yes, there were a few individuals who may have had decreased sweat chloride, but the change in sweat chloride was NOT SUSTAINED through week 40 of the trial. Neither were the gains in fev1.

I'm not saying don't try it, but don't be surprised if your insurance says no. Studies showed that DDF508's had no where near the improvements that g551d had and they will use this to deny coverage.

If you have the time, energy, resources and stamina to fight the system, I encourage you to try. Please keep us updated.

I can send you the chest article in PDF that shows the results of the trial specifically for DDF508s if you want to pm me your email address. This may help you to make a better decision. I had a personal meeting with a Dr. on this study and I may be able to help answer your questions if you have any.

moxie1
05-04-2012, 08:51 AM
I would go for it!
I tried to get my doctor to let me try it, but no go. They said insurance wouldn't cover it even though I told them some others had gotten clearance.
You never know what will happen. Remember, gene modifiers play a big role in things, not just genotype. That's why everyone's course of CF is so different.
I read on another site yesterday that inHolland? (can't remember, so that might not be right) they actually test to see if any CFTR is being potentiated and that with some DDF08 patients it is. Kalydeco would then work for them!
I looked for a link to this info, but I can't find it. I was all over the place yesterday looking up CF/Kalydeco stuff so I have no idea where I saw it. <img src="i/expressions/face-icon-small-sad.gif" border="0">

moxie1
05-04-2012, 08:51 AM
I would go for it!
I tried to get my doctor to let me try it, but no go. They said insurance wouldn't cover it even though I told them some others had gotten clearance.
You never know what will happen. Remember, gene modifiers play a big role in things, not just genotype. That's why everyone's course of CF is so different.
I read on another site yesterday that inHolland? (can't remember, so that might not be right) they actually test to see if any CFTR is being potentiated and that with some DDF08 patients it is. Kalydeco would then work for them!
I looked for a link to this info, but I can't find it. I was all over the place yesterday looking up CF/Kalydeco stuff so I have no idea where I saw it. <img src="i/expressions/face-icon-small-sad.gif" border="0">

musclemania70
05-04-2012, 01:11 PM
Emailed the pdf to individuals who requested it. Let me know if it you didn't get it.

Gene modifiers CAN affect the course of CFTR. Its just that there has been no way to get this data broken down and collected to provide a case for DDF508s with these modifiers...

musclemania70
05-04-2012, 01:11 PM
Emailed the pdf to individuals who requested it. Let me know if it you didn't get it.

Gene modifiers CAN affect the course of CFTR. Its just that there has been no way to get this data broken down and collected to provide a case for DDF508s with these modifiers...

Brad
05-04-2012, 01:52 PM
Correct double Df508 had little respond to Kalydeco .
But people with a single copy of Df508 are having marked improvement taking Kalydeco ,VX770.

I am working on getting it myself.

Brad
05-04-2012, 01:52 PM
Correct double Df508 had little respond to Kalydeco .
But people with a single copy of Df508 are having marked improvement taking Kalydeco ,VX770.

I am working on getting it myself.

zaj1139
05-04-2012, 02:07 PM
My grandson has 3 mutations, but one is Delta F508 the other is R560K and Y569C ? Does that make sense? Ican't figure out how to tell the mutation (c.1679G&gt;A and 1706A&gt;G). Do you think since he has the DF508,that Kalydeco would be worth a try? He is 4 and on Medicaid

zaj1139
05-04-2012, 02:07 PM
My grandson has 3 mutations, but one is Delta F508 the other is R560K and Y569C ? Does that make sense? Ican't figure out how to tell the mutation (c.1679G&gt;A and 1706A&gt;G). Do you think since he has the DF508,that Kalydeco would be worth a try? He is 4 and on Medicaid

rmotion
05-04-2012, 04:30 PM
Here is the rub. I was able to get my cf doc to write a script but insurance says no, not G551. But my beef is how clinic and the CFF handles this. I know the research says that vx770 it doesnt do anything for 508's but it is how the attitude is we are not going help you get it to try. Their hands are tied they do not want to rock the CFF boat.
So why if this is the 1st drug ever to treat CF are they not just trying it on everyone - the cost, the backlash of a let down that it is not a homerun on its own. IT is very frustrating - its like asking a drowning man how to swim - we are drowning and have to tread rough waters on our own.
So here is how it will play out. VX770 is the first step at $1000 per day then next step (we leapfrogged over vx809) to VX661 (which is at best 2 years away) and the protocol will be vx770 and vx661 at $3000 per day -is it all about a bigger payout?
Please let me hear your viewpoints. Is it worth trying VX770 on its own, I would think yes. Again I make the baseball analogy - I just need a base hit, hell I just want out of the F'ing dugout!

rmotion
05-04-2012, 04:30 PM
Here is the rub. I was able to get my cf doc to write a script but insurance says no, not G551. But my beef is how clinic and the CFF handles this. I know the research says that vx770 it doesnt do anything for 508's but it is how the attitude is we are not going help you get it to try. Their hands are tied they do not want to rock the CFF boat.
So why if this is the 1st drug ever to treat CF are they not just trying it on everyone - the cost, the backlash of a let down that it is not a homerun on its own. IT is very frustrating - its like asking a drowning man how to swim - we are drowning and have to tread rough waters on our own.
So here is how it will play out. VX770 is the first step at $1000 per day then next step (we leapfrogged over vx809) to VX661 (which is at best 2 years away) and the protocol will be vx770 and vx661 at $3000 per day -is it all about a bigger payout?
Please let me hear your viewpoints. Is it worth trying VX770 on its own, I would think yes. Again I make the baseball analogy - I just need a base hit, hell I just want out of the F'ing dugout!

rmotion
05-04-2012, 04:32 PM
<strong>creation301</strong><img src="i/dominant/trans.gif" alt=" " width="1" height="8" border="0" />That makes all the difference at least your doc is pushing for you. I had the opposite experience and felt like I had to bring it up I had to push I had to beg. And then when I needed more help they said they are not going to do anything for me - I am on my own with this. Anyway I can have my doc talk to your doc?

rmotion
05-04-2012, 04:32 PM
<strong>creation301</strong><img src="i/dominant/trans.gif" alt=" " width="1" height="8" border="0" />That makes all the difference at least your doc is pushing for you. I had the opposite experience and felt like I had to bring it up I had to push I had to beg. And then when I needed more help they said they are not going to do anything for me - I am on my own with this. Anyway I can have my doc talk to your doc?

rmotion
05-04-2012, 04:36 PM
.....DDF508 did not respond to Kalydeco for the most part. Yes, there were a few individuals who may have had decreased sweat chloride, but the change in sweat chloride was NOT SUSTAINED through week 40 of the trial. Neither were the gains in fev1. I'm not saying don't try it, but don't be surprised if your insurance says no. Studies showed that DDF508's had no where near the improvements that g551d had and they will use this to deny coverage.

Well the devil is in the details. F508's had no where near the improvements, but wait there was some improvement 3-8% - hello that is something to hold onto. NOt enough to get a new drug approved but I'll take a small improvement over what we have now! right?
This is the crux of the argument we need to make. Not a homerun but there could be some help !

rmotion
05-04-2012, 04:36 PM
.....DDF508 did not respond to Kalydeco for the most part. Yes, there were a few individuals who may have had decreased sweat chloride, but the change in sweat chloride was NOT SUSTAINED through week 40 of the trial. Neither were the gains in fev1. I'm not saying don't try it, but don't be surprised if your insurance says no. Studies showed that DDF508's had no where near the improvements that g551d had and they will use this to deny coverage.

Well the devil is in the details. F508's had no where near the improvements, but wait there was some improvement 3-8% - hello that is something to hold onto. NOt enough to get a new drug approved but I'll take a small improvement over what we have now! right?
This is the crux of the argument we need to make. Not a homerun but there could be some help !

musclemania70
05-04-2012, 04:55 PM
Doctors should not be writing the script according to the CFF if the patient does not have g551d. Can't get mad at the docs for saying no.....

Heterozygotes are a completely different story---they have and do show benefit from Kalydeco even if they don't have g551d.
The OP was discussing homozygotes only.

musclemania70
05-04-2012, 04:55 PM
Doctors should not be writing the script according to the CFF if the patient does not have g551d. Can't get mad at the docs for saying no.....

Heterozygotes are a completely different story---they have and do show benefit from Kalydeco even if they don't have g551d.
The OP was discussing homozygotes only.

saveferris2009
05-04-2012, 08:31 PM
There was a subset of DDF508 that showed improvement.

The bottom line is that all patients respond differently - and there is NO REASON not to give the medication a try.

Even a small improvement is worth it. If insurance will pay for it, why not try? If it doesn't work, then you can stop if you want.

I'm so so grateful I tried.

So many things influence clinical outcome - foods you eat, exercise, environment. Even people with the exact same genes don't respond to Kaly the same.

I think it's just a philosophy on life - as long as something is safe, and wow Kaly is very safe, why not give it a try?

saveferris2009
05-04-2012, 08:31 PM
There was a subset of DDF508 that showed improvement.

The bottom line is that all patients respond differently - and there is NO REASON not to give the medication a try.

Even a small improvement is worth it. If insurance will pay for it, why not try? If it doesn't work, then you can stop if you want.

I'm so so grateful I tried.

So many things influence clinical outcome - foods you eat, exercise, environment. Even people with the exact same genes don't respond to Kaly the same.

I think it's just a philosophy on life - as long as something is safe, and wow Kaly is very safe, why not give it a try?

bigstar
05-05-2012, 12:11 PM
saveferris2009 why dont you make a new update in your blog?

bigstar
05-05-2012, 12:11 PM
saveferris2009 why dont you make a new update in your blog?

cfsucks
05-05-2012, 03:58 PM
this medication should be available to everyone with cf- it should be done on a trial basis- everyone gets it for 2 months and if it works they can stay on it.

can't we as the cf community do something about this? there is a large number of us- combined with our family and friends- we should push for this and work together! i feel we could make a difference! people need to be made aware of this drug and it's benefits.

cfsucks
05-05-2012, 03:58 PM
this medication should be available to everyone with cf- it should be done on a trial basis- everyone gets it for 2 months and if it works they can stay on it.

can't we as the cf community do something about this? there is a large number of us- combined with our family and friends- we should push for this and work together! i feel we could make a difference! people need to be made aware of this drug and it's benefits.

saveferris2009
05-05-2012, 11:07 PM
I have truly rarely see people get denied for the Rx - most people that post or that i hear from are getting approved!

saveferris2009
05-05-2012, 11:07 PM
I have truly rarely see people get denied for the Rx - most people that post or that i hear from are getting approved!

JoyousMom
05-06-2012, 02:07 PM
Does anyone have any practical suggestions for working together as a group to put pressure on the CFF to allow Kalydeco trials for more than just a handful of CF'ers? Isn't it time we ALL banded together and made our collective voices heard?! How long will each one of us struggle against the demands and limitations of our personal health insurance, our single CF clinics and doctors? Surely we can do more together than apart.
Letters to Congressmen? Letters to CF Clinics? Newspaper, radio etc.?
Practical suggestions, anyone?

JoyousMom
05-06-2012, 02:07 PM
Does anyone have any practical suggestions for working together as a group to put pressure on the CFF to allow Kalydeco trials for more than just a handful of CF'ers? Isn't it time we ALL banded together and made our collective voices heard?! How long will each one of us struggle against the demands and limitations of our personal health insurance, our single CF clinics and doctors? Surely we can do more together than apart.
Letters to Congressmen? Letters to CF Clinics? Newspaper, radio etc.?
Practical suggestions, anyone?

musclemania70
05-06-2012, 03:42 PM
What exactly do you want them to do? They are doing a Kalydeco trial right now for DDF508. Two actually.

musclemania70
05-06-2012, 03:42 PM
What exactly do you want them to do? They are doing a Kalydeco trial right now for DDF508. Two actually.

saveferris2009
05-06-2012, 04:01 PM
<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>JoyousMom</b></i> Does anyone have any practical suggestions for working together as a group to put pressure on the CFF to allow Kalydeco trials for more than just a handful of CF'ers? Isn't it time we ALL banded together and made our collective voices heard?! How long will each one of us struggle against the demands and limitations of our personal health insurance, our single CF clinics and doctors? Surely we can do more together than apart. Letters to Congressmen? Letters to CF Clinics? Newspaper, radio etc.? Practical suggestions, anyone?</end quote>
I would go to another CF clinic if I had to.
If your doc is holding you back, rather than the insurance, I would for sure fly/drive/train to another clinic to get a hold of the drug. No one can do that for you - you have to do that.
If it's your insurance (rarely have I seen anyone deny it....but if yours did, Iw ould like to hear about it as well), then you can appeal to your state's insurance regulator.
Once each and every CFer has exhausted these measures, THEN i think we can go down the road you are talking about. But I feel most CFer's are simply told "no" by their doc and they just stop there. That's unacceptable, in my opinion. If you want the drug, there are many more steps you can take to get the drug

saveferris2009
05-06-2012, 04:01 PM
<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>JoyousMom</b></i> Does anyone have any practical suggestions for working together as a group to put pressure on the CFF to allow Kalydeco trials for more than just a handful of CF'ers? Isn't it time we ALL banded together and made our collective voices heard?! How long will each one of us struggle against the demands and limitations of our personal health insurance, our single CF clinics and doctors? Surely we can do more together than apart. Letters to Congressmen? Letters to CF Clinics? Newspaper, radio etc.? Practical suggestions, anyone?</end quote>
I would go to another CF clinic if I had to.
If your doc is holding you back, rather than the insurance, I would for sure fly/drive/train to another clinic to get a hold of the drug. No one can do that for you - you have to do that.
If it's your insurance (rarely have I seen anyone deny it....but if yours did, Iw ould like to hear about it as well), then you can appeal to your state's insurance regulator.
Once each and every CFer has exhausted these measures, THEN i think we can go down the road you are talking about. But I feel most CFer's are simply told "no" by their doc and they just stop there. That's unacceptable, in my opinion. If you want the drug, there are many more steps you can take to get the drug

musclemania70
05-06-2012, 09:51 PM
If you intend to try Kalydeco as a DDF508 or other mutation, then you'll need to find a doctor who will write the script for it.
There are doctors that are out there that ARE writing the script no matter the mutation. Just as Amy said, most people just take 'no' for an answer and stop trying.
If you want to pursue it, then continue to call and hunt down a doctor who will let you try it.

EVERYONE should have the chance to give it a shot if they feel it could help them.

musclemania70
05-06-2012, 09:51 PM
If you intend to try Kalydeco as a DDF508 or other mutation, then you'll need to find a doctor who will write the script for it.
There are doctors that are out there that ARE writing the script no matter the mutation. Just as Amy said, most people just take 'no' for an answer and stop trying.
If you want to pursue it, then continue to call and hunt down a doctor who will let you try it.

EVERYONE should have the chance to give it a shot if they feel it could help them.

JENNYC
05-07-2012, 03:48 PM
saveferris2009 so I see that you tried...did it not work for you? Did you have any improvements while on it? thanks

JENNYC
05-07-2012, 03:48 PM
saveferris2009 so I see that you tried...did it not work for you? Did you have any improvements while on it? thanks

rmotion
05-07-2012, 04:33 PM
It seems that they were having minimal response on the VX770/809 combo and now they are saying good results.
ANyone have input?


Interim Data from Phase 2 Combination Study of VX-809 and KALYDECOtm (ivacaftor) Showed Significant Improvements in Lung Function (FEV1) in People with Cystic Fibrosis Who Have Two Copies of the F508del Mutation
Vertex Pharmaceuticals IncorporatedPosted on:07 May 12.
More Vertex Pharmaceuticals Incorporated press releases


Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today an interim analysis of data from an ongoing Phase 2 study of VX-809 and KALYDECOtm (ivacaftor) that showed significant improvements in lung function (FEV1) among adults with cystic fibrosis (CF) who have two copies (homozygous) of the most common mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, F508del. A planned interim analysis was conducted after approximately half of the study patients had completed 56 days of treatment. Today's results are based on data from 37 homozygous F508del patients who completed treatment in the 56-day study and 11 patients with one or two copies of the F508del mutation who received placebo. There was a statistically significant improvement in lung function (absolute change in percent predicted FEV1) across the combined treatment groups relative to baseline compared to placebo (p=0.002). Of those who received VX-809 and KALYDECO (250mg, q12h), approximately 46 percent (17/37) experienced an absolute improvement from baseline to Day 56 in lung function of 5 percentage points or more, and approximately 30 percent (11/37) experienced an absolute improvement from baseline to Day 56 of 10 percentage points or more. None of the patients treated with placebo (0/11) achieved a 5-percentage point or more improvement from baseline to Day 56 in lung function. Most adverse events were mild or moderate in severity and comparable between treatment and placebo groups.

The study is ongoing and complete data, including statistical analyses for all patient groups, will be available in mid-2012. Vertex plans to start a pivotal study of VX-809 and KALYDECO in people with two copies of the F508del mutation, pending final study results and discussions with regulatory agencies. Evaluation of patients with one copy (heterozygous, n=21) of the F508del mutation is ongoing, but at the time of this interim analysis not enough patients had completed the study to make any conclusions. These complete data will be included in the final study analysis and will be used to determine next steps for the development of VX-809 and KALYDECO in heterozygous F508del patients. Vertex will host a conference call for investors and media today, May 7, 2012 at 8:30 a.m. ET to discuss this interim data analysis.

Cystic fibrosis is a rare, life threatening genetic disease affecting approximately 30,000 people in the United States and 70,000 people worldwide. Nearly half of those with CF are estimated to have two copies of the F508del mutation.

"For the past 14 years, our teams have focused on learning about the underlying cause of cystic fibrosis so we can develop new medicines to help as many patients as possible. Today we believe we're one step closer to this goal," said Chris Wright, M.D., Ph.D., Vertex's Senior Vice President, Global Medicines Development and Medical Affairs. "People with two copies of the F508del mutation have one of the most severe forms of cystic fibrosis. In these patients, the combination of VX-809 and KALYDECO led to significant improvements in lung function that exceeded our expectations. We look forward to beginning discussions with regulatory agencies later this year when we have full data from the study, with the goal of moving forward with a pivotal study as quickly as possible."

"Lung function is the single most important marker of disease progression for people with cystic fibrosis, and improvement in lung function is the goal of every new CF therapy," said Michael P. Boyle, M.D, FCCP, Associate Professor of Medicine, Director of the Johns Hopkins Adult Cystic Fibrosis Center, and lead investigator for this study. "While we still eagerly await the results from the remainder of the trial, we are definitely encouraged that this interim analysis showed a significant improvement in lung function in people with two copies of the F508del mutation who received VX-809 and KALYDECO."

Interim Results

Data from the first part of this study were announced in 2011. The interim data announced today are from the second part of the ongoing Phase 2 randomized, double-blind, placebo-controlled study. This part of the study enrolled 108 people with CF ages 18 and older with one or two copies of the F508del mutation who were divided into five treatment groups of approximately 20 patients each. Three groups of homozygous patients were randomized to receive VX-809 alone (200mg, 400mg or 600mg) for 28 days and then in combination with KALYDECO (250mg) for an additional 28 days. One group of heterozygous patients is receiving VX-809 alone (600mg) for 28 days and then in combination with KALYDECO (250mg) for an additional 28 days. The placebo group includes both homozygous and heterozygous patients.

Lung function: Progressive lung disease is a major source of illness and is the leading cause of death in people with CF. Typically people with CF lose 1 percent to 2 percent of their lung function (FEV1) each year.

Improvements in lung function (absolute change in percent predicted FEV1) were observed in all combination treatment dose groups in homozygous patients. The percent of patients who experienced absolute improvement from baseline in lung function was as follows:



Treatment Group




Absolute Improvement from Baseline in Lung Function (FEV1)(Baseline - Day 56)







= 5 percentage points

= 10 percentage points




VX-809 alone (200mg, 400mg or 600mg)for 28 days followed by KALYDECO(250mg, q12h) + VX-809 (200mg, 400mg,600mg dose groups combined)for 28 days




46% (17/37)

30% (11/37)



Placebo



0 (0/11)

0 (0/11)









Sweat chloride: Elevated sweat chloride levels are a diagnostic hallmark in CF and are the result of CFTR protein dysfunction. Although not a clinically validated endpoint, a reduction in sweat chloride is considered to be a biomarker of improved CFTR function in the skin.

One of the two primary endpoints in this study is change in sweat chloride from Day 28 to Day 56. Reductions in sweat chloride were observed between Day 28 and Day 56 in homozygous patients treated with VX-809 and KALYDECO. At the time of this interim analysis, these reductions were not statistically significant.

A statistically significant reduction in sweat chloride was observed in patients treated with VX-809 alone (baseline - Day 28).

Safety: A co-primary endpoint in this study is safety. Safety results reported today include data from all patients who had started treatment prior to this interim analysis. VX-809 was generally well tolerated alone and in combination with KALYDECO. The most common adverse events were pulmonary in nature. Most adverse events were mild or moderate in severity and comparable between treatment and placebo groups. The rate of serious adverse events was similar between treatment and placebo groups.

Cystic fibrosis is caused by defective or missing CFTR proteins resulting from mutations in the CFTR gene. Located at the surface of cells, CFTR proteins act as channels to regulate the flow of salt and water into and out of the cells. In people with the F508del mutation in the CFTR gene, little to no CFTR protein reaches the cell surface. As a result, thick, sticky mucus builds up and blocks the passages in many organs, leading to a variety of symptoms. In particular, mucus builds up and clogs the airways in the lungs, causing chronic lung infections and progressive lung damage. VX-809, known as a CFTR corrector, is believed to help CFTR proteins reach the cell surface. KALYDECO, known as a CFTR potentiator, keeps the CFTR protein channels open longer to increase the flow of salt and water into and out of the cell.

VX-809 and KALYDECO were discovered as part of collaboration with Cystic Fibrosis Foundation Therapeutics, Inc., the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation.

Conference Call for Media and Investors

Vertex will host a conference call and webcast today, May 7, 2012 at 8:30 a.m. ET to discuss this interim data analysis. The conference call will be webcast live and a link to the webcast may be accessed from the 'Events & Presentations' page of the Vertex website at www.vrtx.com.

To listen to the live call on the telephone, dial 1-866-501-1537 (United States and Canada) or 1-720-545-0001 (International). To ensure a timely connection, it is recommended that users register at least 15 minutes prior to the scheduled webcast.

The conference ID number for the live call and replay is 78832581.

The call will be available for replay via telephone commencing May 7, 2012 at 11:30 a.m. ET running through 5:00 p.m. ET on May 14, 2012. The replay phone number for the United States and Canada is 1-855-859-2056. The international replay number is 1-404-537-3406.

Following the live webcast, an archived version will be available on Vertex's website until 5:00 p.m. ET on May 21, 2012. Vertex is also providing a podcast MP3 file available for download on the Vertex website at www.vrtx.com.

About Cystic Fibrosis

Cystic fibrosis is a rare, life-threatening genetic disease affecting approximately 30,000 people in the United States and 70,000 people worldwide. Today, the median predicted age of survival for a person with CF is approximately 38 years but the median age of death remains in the mid-20s. There are more than 1,800 known mutations in the CFTR gene. Some of these mutations, which can be determined by a genetic, or genotyping test, lead to CF by creating non-working or too few CFTR proteins at the cell surface. The absence of working CFTR proteins results in poor flow of salt and water into and out of the cell in a number of organs, including the lungs.

In people with the most common mutation in the CFTR gene, F508del, little to no CFTR protein reaches the cell surface. Globally, nearly half (46 percent) of people with CF have two copies of the F508del mutation and one-third (33 percent) have one copy of the F508del mutation.

About KALYDECO

KALYDECOtm (ivacaftor) is the first treatment to target the underlying cause of CF. KALYDECO (150mg, q12h) was approved by the U.S. Food and Drug Administration (FDA) in January 2012 for use in people with CF ages 6 and older who have at least one copy of the G551D mutation in the CFTR gene.

Vertex retains worldwide rights to develop and commercialize KALYDECO. In October 2011, Vertex submitted a marketing authorization application to the European Medicines Agency (EMA) for KALYDECO and has received agreement from the EMA for accelerated assessment in Europe. The EMA regulatory review is ongoing.

Indication and Important Safety Information

KALYDECO (150mg, q12h) is a prescription medicine used for the treatment of cystic fibrosis (CF) in patients age 6 years and older who have a certain mutation in their CFTR gene called the G551D mutation.

KALYDECO is not for use in people with CF due to other mutations in the CFTR gene. It is not effective in CF patients with two copies of the F508del mutation (F508del/F508del) in the CFTR gene.

It is not known if KALYDECO is safe and effective in children under 6 years of age.

KALYDECO should not be used with certain medicines, including the antibiotics rifampin and rifabutin; seizure medications (phenobarbital, carbamazepine, or phenytoin); and the herbal supplement St. John's Wort.

KALYDECO can cause serious side effects. High liver enzymes in the blood have occurred in patients taking KALYDECO as well as those receiving placebo. Regular assessment is recommended.

The most common side effects associated with KALYDECO include headache; upper respiratory tract infection (common cold) including sore throat, nasal or sinus congestion, and runny nose; stomach (abdominal) pain; diarrhea; rash; nausea; and dizziness.

These are not all the possible side effects of KALYDECO. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.

Please see full Prescribing Information for KALYDECO at www.KALYDECO.com.

Collaborative History with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT)

Vertex initiated its CF research program in 1998 as part of a collaboration with CFFT, the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. This collaboration was expanded to support the accelerated discovery and development of Vertex's CFTR modulators.

About the Cystic Fibrosis Foundation

The Cystic Fibrosis Foundation is the world's leader in the search for a cure for cystic fibrosis. The Foundation funds more CF research than any other organization and nearly every CF drug available today was made possible because of Foundation support. Based in Bethesda, Md., the Foundation also supports and accredits a national care center network that has been recognized by the National Institutes of Health as a model of care for a chronic disease. The CF Foundation is a donor-supported nonprofit organization. For more information, visit www.cff.org.

About Vertex

Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.

Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis, epilepsy and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 2,000 employees around the world, and Science magazine named Vertex number one on its 2011 list of Top Employers in the life sciences.

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including Dr. Wright's and Dr. Boyle's statements in the fourth and fifth paragraphs of this press release, and statements regarding (i) Vertex's plan to start a pivotal study of VX-809 and KALYDECO in people with two copies of the F508del mutation, pending final data and discussions with regulatory agencies, (ii) the expected availability of complete data from the study in mid-2012 and (iii) the expectation that the final data that will become available in mid-2012 will be used to determine next steps for the development of VX-809 and KALYDECO in heterozygous F508del patients. While Vertex believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the final outcomes of this clinical trial or future clinical trials of VX-809 and KALYDECO may be less favorable than the interim analysis reported today, or may not be favorable at all, that final data from heterozygous patients may not be favorable or may be less favorable than the data from homozygous patients, that final data and/or discussions with regulatory agencies regarding the scope and design of future clinical trials may result in additional clinical trials needing to be conducted before Vertex can initiate the first pivotal clinical trials evaluating VX-809 in combination with KALYDECO and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company's website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)
.

Read more: http://www.pharmiweb.com/PressReleases/pressrel.asp?ROW_ID=58162#ixzz1uD32ls1p

rmotion
05-07-2012, 04:33 PM
It seems that they were having minimal response on the VX770/809 combo and now they are saying good results.
ANyone have input?


Interim Data from Phase 2 Combination Study of VX-809 and KALYDECOtm (ivacaftor) Showed Significant Improvements in Lung Function (FEV1) in People with Cystic Fibrosis Who Have Two Copies of the F508del Mutation
Vertex Pharmaceuticals IncorporatedPosted on:07 May 12.
More Vertex Pharmaceuticals Incorporated press releases


Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today an interim analysis of data from an ongoing Phase 2 study of VX-809 and KALYDECOtm (ivacaftor) that showed significant improvements in lung function (FEV1) among adults with cystic fibrosis (CF) who have two copies (homozygous) of the most common mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, F508del. A planned interim analysis was conducted after approximately half of the study patients had completed 56 days of treatment. Today's results are based on data from 37 homozygous F508del patients who completed treatment in the 56-day study and 11 patients with one or two copies of the F508del mutation who received placebo. There was a statistically significant improvement in lung function (absolute change in percent predicted FEV1) across the combined treatment groups relative to baseline compared to placebo (p=0.002). Of those who received VX-809 and KALYDECO (250mg, q12h), approximately 46 percent (17/37) experienced an absolute improvement from baseline to Day 56 in lung function of 5 percentage points or more, and approximately 30 percent (11/37) experienced an absolute improvement from baseline to Day 56 of 10 percentage points or more. None of the patients treated with placebo (0/11) achieved a 5-percentage point or more improvement from baseline to Day 56 in lung function. Most adverse events were mild or moderate in severity and comparable between treatment and placebo groups.

The study is ongoing and complete data, including statistical analyses for all patient groups, will be available in mid-2012. Vertex plans to start a pivotal study of VX-809 and KALYDECO in people with two copies of the F508del mutation, pending final study results and discussions with regulatory agencies. Evaluation of patients with one copy (heterozygous, n=21) of the F508del mutation is ongoing, but at the time of this interim analysis not enough patients had completed the study to make any conclusions. These complete data will be included in the final study analysis and will be used to determine next steps for the development of VX-809 and KALYDECO in heterozygous F508del patients. Vertex will host a conference call for investors and media today, May 7, 2012 at 8:30 a.m. ET to discuss this interim data analysis.

Cystic fibrosis is a rare, life threatening genetic disease affecting approximately 30,000 people in the United States and 70,000 people worldwide. Nearly half of those with CF are estimated to have two copies of the F508del mutation.

"For the past 14 years, our teams have focused on learning about the underlying cause of cystic fibrosis so we can develop new medicines to help as many patients as possible. Today we believe we're one step closer to this goal," said Chris Wright, M.D., Ph.D., Vertex's Senior Vice President, Global Medicines Development and Medical Affairs. "People with two copies of the F508del mutation have one of the most severe forms of cystic fibrosis. In these patients, the combination of VX-809 and KALYDECO led to significant improvements in lung function that exceeded our expectations. We look forward to beginning discussions with regulatory agencies later this year when we have full data from the study, with the goal of moving forward with a pivotal study as quickly as possible."

"Lung function is the single most important marker of disease progression for people with cystic fibrosis, and improvement in lung function is the goal of every new CF therapy," said Michael P. Boyle, M.D, FCCP, Associate Professor of Medicine, Director of the Johns Hopkins Adult Cystic Fibrosis Center, and lead investigator for this study. "While we still eagerly await the results from the remainder of the trial, we are definitely encouraged that this interim analysis showed a significant improvement in lung function in people with two copies of the F508del mutation who received VX-809 and KALYDECO."

Interim Results

Data from the first part of this study were announced in 2011. The interim data announced today are from the second part of the ongoing Phase 2 randomized, double-blind, placebo-controlled study. This part of the study enrolled 108 people with CF ages 18 and older with one or two copies of the F508del mutation who were divided into five treatment groups of approximately 20 patients each. Three groups of homozygous patients were randomized to receive VX-809 alone (200mg, 400mg or 600mg) for 28 days and then in combination with KALYDECO (250mg) for an additional 28 days. One group of heterozygous patients is receiving VX-809 alone (600mg) for 28 days and then in combination with KALYDECO (250mg) for an additional 28 days. The placebo group includes both homozygous and heterozygous patients.

Lung function: Progressive lung disease is a major source of illness and is the leading cause of death in people with CF. Typically people with CF lose 1 percent to 2 percent of their lung function (FEV1) each year.

Improvements in lung function (absolute change in percent predicted FEV1) were observed in all combination treatment dose groups in homozygous patients. The percent of patients who experienced absolute improvement from baseline in lung function was as follows:



Treatment Group




Absolute Improvement from Baseline in Lung Function (FEV1)(Baseline - Day 56)







= 5 percentage points

= 10 percentage points




VX-809 alone (200mg, 400mg or 600mg)for 28 days followed by KALYDECO(250mg, q12h) + VX-809 (200mg, 400mg,600mg dose groups combined)for 28 days




46% (17/37)

30% (11/37)



Placebo



0 (0/11)

0 (0/11)









Sweat chloride: Elevated sweat chloride levels are a diagnostic hallmark in CF and are the result of CFTR protein dysfunction. Although not a clinically validated endpoint, a reduction in sweat chloride is considered to be a biomarker of improved CFTR function in the skin.

One of the two primary endpoints in this study is change in sweat chloride from Day 28 to Day 56. Reductions in sweat chloride were observed between Day 28 and Day 56 in homozygous patients treated with VX-809 and KALYDECO. At the time of this interim analysis, these reductions were not statistically significant.

A statistically significant reduction in sweat chloride was observed in patients treated with VX-809 alone (baseline - Day 28).

Safety: A co-primary endpoint in this study is safety. Safety results reported today include data from all patients who had started treatment prior to this interim analysis. VX-809 was generally well tolerated alone and in combination with KALYDECO. The most common adverse events were pulmonary in nature. Most adverse events were mild or moderate in severity and comparable between treatment and placebo groups. The rate of serious adverse events was similar between treatment and placebo groups.

Cystic fibrosis is caused by defective or missing CFTR proteins resulting from mutations in the CFTR gene. Located at the surface of cells, CFTR proteins act as channels to regulate the flow of salt and water into and out of the cells. In people with the F508del mutation in the CFTR gene, little to no CFTR protein reaches the cell surface. As a result, thick, sticky mucus builds up and blocks the passages in many organs, leading to a variety of symptoms. In particular, mucus builds up and clogs the airways in the lungs, causing chronic lung infections and progressive lung damage. VX-809, known as a CFTR corrector, is believed to help CFTR proteins reach the cell surface. KALYDECO, known as a CFTR potentiator, keeps the CFTR protein channels open longer to increase the flow of salt and water into and out of the cell.

VX-809 and KALYDECO were discovered as part of collaboration with Cystic Fibrosis Foundation Therapeutics, Inc., the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation.

Conference Call for Media and Investors

Vertex will host a conference call and webcast today, May 7, 2012 at 8:30 a.m. ET to discuss this interim data analysis. The conference call will be webcast live and a link to the webcast may be accessed from the 'Events & Presentations' page of the Vertex website at www.vrtx.com.

To listen to the live call on the telephone, dial 1-866-501-1537 (United States and Canada) or 1-720-545-0001 (International). To ensure a timely connection, it is recommended that users register at least 15 minutes prior to the scheduled webcast.

The conference ID number for the live call and replay is 78832581.

The call will be available for replay via telephone commencing May 7, 2012 at 11:30 a.m. ET running through 5:00 p.m. ET on May 14, 2012. The replay phone number for the United States and Canada is 1-855-859-2056. The international replay number is 1-404-537-3406.

Following the live webcast, an archived version will be available on Vertex's website until 5:00 p.m. ET on May 21, 2012. Vertex is also providing a podcast MP3 file available for download on the Vertex website at www.vrtx.com.

About Cystic Fibrosis

Cystic fibrosis is a rare, life-threatening genetic disease affecting approximately 30,000 people in the United States and 70,000 people worldwide. Today, the median predicted age of survival for a person with CF is approximately 38 years but the median age of death remains in the mid-20s. There are more than 1,800 known mutations in the CFTR gene. Some of these mutations, which can be determined by a genetic, or genotyping test, lead to CF by creating non-working or too few CFTR proteins at the cell surface. The absence of working CFTR proteins results in poor flow of salt and water into and out of the cell in a number of organs, including the lungs.

In people with the most common mutation in the CFTR gene, F508del, little to no CFTR protein reaches the cell surface. Globally, nearly half (46 percent) of people with CF have two copies of the F508del mutation and one-third (33 percent) have one copy of the F508del mutation.

About KALYDECO

KALYDECOtm (ivacaftor) is the first treatment to target the underlying cause of CF. KALYDECO (150mg, q12h) was approved by the U.S. Food and Drug Administration (FDA) in January 2012 for use in people with CF ages 6 and older who have at least one copy of the G551D mutation in the CFTR gene.

Vertex retains worldwide rights to develop and commercialize KALYDECO. In October 2011, Vertex submitted a marketing authorization application to the European Medicines Agency (EMA) for KALYDECO and has received agreement from the EMA for accelerated assessment in Europe. The EMA regulatory review is ongoing.

Indication and Important Safety Information

KALYDECO (150mg, q12h) is a prescription medicine used for the treatment of cystic fibrosis (CF) in patients age 6 years and older who have a certain mutation in their CFTR gene called the G551D mutation.

KALYDECO is not for use in people with CF due to other mutations in the CFTR gene. It is not effective in CF patients with two copies of the F508del mutation (F508del/F508del) in the CFTR gene.

It is not known if KALYDECO is safe and effective in children under 6 years of age.

KALYDECO should not be used with certain medicines, including the antibiotics rifampin and rifabutin; seizure medications (phenobarbital, carbamazepine, or phenytoin); and the herbal supplement St. John's Wort.

KALYDECO can cause serious side effects. High liver enzymes in the blood have occurred in patients taking KALYDECO as well as those receiving placebo. Regular assessment is recommended.

The most common side effects associated with KALYDECO include headache; upper respiratory tract infection (common cold) including sore throat, nasal or sinus congestion, and runny nose; stomach (abdominal) pain; diarrhea; rash; nausea; and dizziness.

These are not all the possible side effects of KALYDECO. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.

Please see full Prescribing Information for KALYDECO at www.KALYDECO.com.

Collaborative History with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT)

Vertex initiated its CF research program in 1998 as part of a collaboration with CFFT, the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. This collaboration was expanded to support the accelerated discovery and development of Vertex's CFTR modulators.

About the Cystic Fibrosis Foundation

The Cystic Fibrosis Foundation is the world's leader in the search for a cure for cystic fibrosis. The Foundation funds more CF research than any other organization and nearly every CF drug available today was made possible because of Foundation support. Based in Bethesda, Md., the Foundation also supports and accredits a national care center network that has been recognized by the National Institutes of Health as a model of care for a chronic disease. The CF Foundation is a donor-supported nonprofit organization. For more information, visit www.cff.org.

About Vertex

Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.

Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis, epilepsy and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 2,000 employees around the world, and Science magazine named Vertex number one on its 2011 list of Top Employers in the life sciences.

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including Dr. Wright's and Dr. Boyle's statements in the fourth and fifth paragraphs of this press release, and statements regarding (i) Vertex's plan to start a pivotal study of VX-809 and KALYDECO in people with two copies of the F508del mutation, pending final data and discussions with regulatory agencies, (ii) the expected availability of complete data from the study in mid-2012 and (iii) the expectation that the final data that will become available in mid-2012 will be used to determine next steps for the development of VX-809 and KALYDECO in heterozygous F508del patients. While Vertex believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the final outcomes of this clinical trial or future clinical trials of VX-809 and KALYDECO may be less favorable than the interim analysis reported today, or may not be favorable at all, that final data from heterozygous patients may not be favorable or may be less favorable than the data from homozygous patients, that final data and/or discussions with regulatory agencies regarding the scope and design of future clinical trials may result in additional clinical trials needing to be conducted before Vertex can initiate the first pivotal clinical trials evaluating VX-809 in combination with KALYDECO and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company's website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)
.

Read more: http://www.pharmiweb.com/PressReleases/pressrel.asp?ROW_ID=58162#ixzz1uD32ls1p

musclemania70
05-07-2012, 04:37 PM
Thanks for posting this update! Here is the link for anyone who wants to read it from the web.

http://investors.vrtx.com/releasedetail.cfm?ReleaseID=670755

musclemania70
05-07-2012, 04:37 PM
Thanks for posting this update! Here is the link for anyone who wants to read it from the web.

http://investors.vrtx.com/releasedetail.cfm?ReleaseID=670755