DF508ers who participated in VX-770 trials

[Havoc]

<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>Incomudrox</b></i> <div class="FTQUOTE"><begin quote><i>Originally posted by: <b>kyrock85</b></i> I participated in the study (i'm homozygous df508). In the begining I wasn't suppose to be able to see what my PFTs were (they were pretty good about keepin that info hidden). I was on the drug from January 2010 until june 2011 when they pulled it for not showing enough significant data. I can tell you that when I had to try 2 times to get into the study. Like I said, for about 6 months I wasn't allowed to know what my PFTS were, but I can tell you that you that it was a whole heck of a lot easier to breath, I had decrease cough, my mucous was thinner, and I put on weight like it was job! After beign on the study for 6 months, I was switched to part B. To continue and switch to part b you had to meet one of 3 outcomes. Increase PFT by i believe 10%, change in sweat chlorides, and I forget the 3rd. I had a change in my sweat chloride. Once switched to part B, I could see my PFTS once again. My PFTs remainded stable ( and much improved from when I began the study). I went from getting clean outs from every 6 months to once a year and now it will have been 21 months on friday. SOOO, does this drug work on ddf508, somewhat. Does it need some kind of help yes.</end quote> Interesting, to me what this means is that there is more to DDF508 and DF508 than we (the people) are being told. It must also have a gating component, or is it that Kalydeco does much more then just fix gating mutations?.... Too many variables.</end quote>

Was this the Phase II study after which they dropped Double Deltas for Phase III consideration?

 

[Havoc]

<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>Incomudrox</b></i> <div class="FTQUOTE"><begin quote><i>Originally posted by: <b>kyrock85</b></i> I participated in the study (i'm homozygous df508). In the begining I wasn't suppose to be able to see what my PFTs were (they were pretty good about keepin that info hidden). I was on the drug from January 2010 until june 2011 when they pulled it for not showing enough significant data. I can tell you that when I had to try 2 times to get into the study. Like I said, for about 6 months I wasn't allowed to know what my PFTS were, but I can tell you that you that it was a whole heck of a lot easier to breath, I had decrease cough, my mucous was thinner, and I put on weight like it was job! After beign on the study for 6 months, I was switched to part B. To continue and switch to part b you had to meet one of 3 outcomes. Increase PFT by i believe 10%, change in sweat chlorides, and I forget the 3rd. I had a change in my sweat chloride. Once switched to part B, I could see my PFTS once again. My PFTs remainded stable ( and much improved from when I began the study). I went from getting clean outs from every 6 months to once a year and now it will have been 21 months on friday. SOOO, does this drug work on ddf508, somewhat. Does it need some kind of help yes.</end quote> Interesting, to me what this means is that there is more to DDF508 and DF508 than we (the people) are being told. It must also have a gating component, or is it that Kalydeco does much more then just fix gating mutations?.... Too many variables.</end quote>

Was this the Phase II study after which they dropped Double Deltas for Phase III consideration?

 

[kyrock85]

the way that my CF research nurse explained my gene mutation to me was that it could be a variety of different things. It could be that the gate jsut doesn't open, it could be that the gate is bent, or a combination. We're assuming i have a combination since the drug did semi work for me. When I started the study i was at about 39% FEV1. I was later told it jumped about 10% within about the first month or two and then it was low forties when I ended the study and I'm currently (as of a month ago) was back to the 39%.

 

[kyrock85]

the way that my CF research nurse explained my gene mutation to me was that it could be a variety of different things. It could be that the gate jsut doesn't open, it could be that the gate is bent, or a combination. We're assuming i have a combination since the drug did semi work for me. When I started the study i was at about 39% FEV1. I was later told it jumped about 10% within about the first month or two and then it was low forties when I ended the study and I'm currently (as of a month ago) was back to the 39%.

 

[Incomudrox]

<div class="FTQUOTE"><begin quote><em>Originally posted by: <strong>kyrock85</strong></em> the way that my CF research nurse explained my gene mutation to me was that it could be a variety of different things. It could be that the gate jsut doesn't open, it could be that the gate is bent, or a combination. We're assuming i have a combination since the drug did semi work for me. When I started the study i was at about 39% FEV1. I was later told it jumped about 10% within about the first month or two and then it was low forties when I ended the study and I'm currently (as of a month ago) was back to the 39%.</end quote>

So you DON'T have DDF508??... As I thought.

 

[Incomudrox]

<div class="FTQUOTE"><begin quote><em>Originally posted by: <strong>kyrock85</strong></em> the way that my CF research nurse explained my gene mutation to me was that it could be a variety of different things. It could be that the gate jsut doesn't open, it could be that the gate is bent, or a combination. We're assuming i have a combination since the drug did semi work for me. When I started the study i was at about 39% FEV1. I was later told it jumped about 10% within about the first month or two and then it was low forties when I ended the study and I'm currently (as of a month ago) was back to the 39%.</end quote>

So you DON'T have DDF508??... As I thought.

 

[cfsucks]

<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>Incomudrox</b></i> <div class="FTQUOTE"><begin quote><i>Originally posted by: <b>kyrock85</b></i> the way that my CF research nurse explained my gene mutation to me was that it could be a variety of different things. It could be that the gate jsut doesn't open, it could be that the gate is bent, or a combination. We're assuming i have a combination since the drug did semi work for me. When I started the study i was at about 39% FEV1. I was later told it jumped about 10% within about the first month or two and then it was low forties when I ended the study and I'm currently (as of a month ago) was back to the 39%.</end quote> So you DON'T have DDF508??... As I thought.</end quote>

i'm confused as well- his signature states homozygous df508, and he said he had ddf508 in his first message, but i'm confused as to why the nurse would describe his mutation as so?

 

[cfsucks]

<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>Incomudrox</b></i> <div class="FTQUOTE"><begin quote><i>Originally posted by: <b>kyrock85</b></i> the way that my CF research nurse explained my gene mutation to me was that it could be a variety of different things. It could be that the gate jsut doesn't open, it could be that the gate is bent, or a combination. We're assuming i have a combination since the drug did semi work for me. When I started the study i was at about 39% FEV1. I was later told it jumped about 10% within about the first month or two and then it was low forties when I ended the study and I'm currently (as of a month ago) was back to the 39%.</end quote> So you DON'T have DDF508??... As I thought.</end quote>

i'm confused as well- his signature states homozygous df508, and he said he had ddf508 in his first message, but i'm confused as to why the nurse would describe his mutation as so?

 

[Keepercjr]

well if he is homozygous then he does have 2 copies of the mutation. However we all have modifier genes that can affect things as well. I just explained in a different thread that my brother and I had the same mutations yet he was pancreatic insufficient and died when he was 13. I am pancreatic sufficient and here I am at 30 years old and doing relatively well.

 

[Keepercjr]

well if he is homozygous then he does have 2 copies of the mutation. However we all have modifier genes that can affect things as well. I just explained in a different thread that my brother and I had the same mutations yet he was pancreatic insufficient and died when he was 13. I am pancreatic sufficient and here I am at 30 years old and doing relatively well.

 

[Havoc]

Epigenetics is not well understood yet by those studying it. I don't think any of us are competent to speculate above the fact that, as you said, some people with nearly the same genes and similar environmental factors have different outcomes.

I think the concern that some of us have is potential confusion and false hope that something is going to work, when it probably wont.

 

[Havoc]

Epigenetics is not well understood yet by those studying it. I don't think any of us are competent to speculate above the fact that, as you said, some people with nearly the same genes and similar environmental factors have different outcomes.

I think the concern that some of us have is potential confusion and false hope that something is going to work, when it probably wont.

 

[kwcf50]

I am interested in finding out if phase 2 clinical trial for 770/809 will be open to those with only one df508. The current study is for double df508s only. If anyone knows....please post. My doc says they don't know.

 

[kwcf50]

I am interested in finding out if phase 2 clinical trial for 770/809 will be open to those with only one df508. The current study is for double df508s only. If anyone knows....please post. My doc says they don't know.

 

[Gammaw]

Has Vertex ever indicated why the current trials include VX770 in combination with the other two drugs in development for DF508? If VX770 (Kalydeco) has no effect on DF508, then why bother. They must feel some potential connection exists. I agree with those that state we do not have sufficient expertise - and the experts do not have sufficient knowledge - to be definitive. I learned a long time ago that the exception defines the rule, and the right answer is almost always a surprise.

 

[Gammaw]

Has Vertex ever indicated why the current trials include VX770 in combination with the other two drugs in development for DF508? If VX770 (Kalydeco) has no effect on DF508, then why bother. They must feel some potential connection exists. I agree with those that state we do not have sufficient expertise - and the experts do not have sufficient knowledge - to be definitive. I learned a long time ago that the exception defines the rule, and the right answer is almost always a surprise.

 

[jdmd]

<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>kwcf50</b></i> I am interested in finding out if phase 2 clinical trial for 770/809 will be open to those with only one df508. The current study is for double df508s only. If anyone knows....please post. My doc says they don't know.</end quote>

One of the five groups in the cohort is for heterozygotes (d508 and certain other alleles). If you have a research team at your center, they should know if you qualify.

 

[jdmd]

<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>kwcf50</b></i> I am interested in finding out if phase 2 clinical trial for 770/809 will be open to those with only one df508. The current study is for double df508s only. If anyone knows....please post. My doc says they don't know.</end quote>

One of the five groups in the cohort is for heterozygotes (d508 and certain other alleles). If you have a research team at your center, they should know if you qualify.

 

[jdmd]

<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>Gammaw</b></i> Has Vertex ever indicated why the current trials include VX770 in combination with the other two drugs in development for DF508? If VX770 (Kalydeco) has no effect on DF508, then why bother. They must feel some potential connection exists. I agree with those that state we do not have sufficient expertise - and the experts do not have sufficient knowledge - to be definitive. I learned a long time ago that the exception defines the rule, and the right answer is almost always a surprise.</end quote>
The df508 gene codes for cftr which has both a folding problem which keeps it from getting to the membrane AND a gating problem. The solution proposed is that either 809 or the other (661?) gets the protein to the membrane, and 770 fixes the gating issue. When a fix to the dd508 genotype occurs, it will have to fix both of these issues, thus it will be a combination of drugs. Hope this helps.

 

[jdmd]

<div class="FTQUOTE"><begin quote><i>Originally posted by: <b>Gammaw</b></i> Has Vertex ever indicated why the current trials include VX770 in combination with the other two drugs in development for DF508? If VX770 (Kalydeco) has no effect on DF508, then why bother. They must feel some potential connection exists. I agree with those that state we do not have sufficient expertise - and the experts do not have sufficient knowledge - to be definitive. I learned a long time ago that the exception defines the rule, and the right answer is almost always a surprise.</end quote>
The df508 gene codes for cftr which has both a folding problem which keeps it from getting to the membrane AND a gating problem. The solution proposed is that either 809 or the other (661?) gets the protein to the membrane, and 770 fixes the gating issue. When a fix to the dd508 genotype occurs, it will have to fix both of these issues, thus it will be a combination of drugs. Hope this helps.