Latest Vertex News: New data for F508del and G551D

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GenH

New member
I have added several new posts to my blog and thought I would add links here.

The first post has new graphs from vertex showing that
1) When a second generation corrector is added to VX809 & Kalydeco, heterozygotes (1 copy F508del) increase to about 33% of normal function (based on data with F508del/G542X) and homozygotes (2 copies F508del) reach about 45%
2) When VX809 is added to Kalydeco with people who have G551D & F508del, they improve from 50% of normal function to 80%

http://sixtyfiverosesblog.wordpress...x-second-generation-correctors-latest-graphs/

The second post is a summary of the latest Vertex investor conference, with the latest info about VX809, VX661 and VX983.

http://sixtyfiverosesblog.wordpress.com/2013/06/12/june-vertex-update/
 
T

triples15

Super Moderator
Thanks GenH for keeping us up to speed! Very exciting stuff indeed!

I'm wondering how this will all play out for those of us with DF508 and a residual function mutation. It is looking likely that these drugs will be approved for homozygous Df508s before the residual function group that's in phase 2 trials now. It is beyond frustrating to me that I will have to wait and wait, when study after study continues to show that these drugs likely work VERY well for my mutation. If I have to wait until it is approved for my specific mutation it could be years. I'm guessing that if/when it is approved for the double deltas it will still be considered off-label for those of us with residual function. Ugh.

I guess what I'm frustrated about is that it seems like those of us that it could help the MOST, now might be last to get it. Ugh.

To be VERY clear though, I am SO happy for double deltas, those are very exciting results. And it will be so awesome if/when approved for them because it will help SO many CFers!!

Gen, what are you thoughts about how the FDA approval process will go down? I guess specifically in regards to how long those of us with a residual function mutation will wait. I'm hoping that somehow if/when it gets approved for the homozygotes we will be able to get our hands on it. But, I fear it will still be considered off-label and will still be out of reach for most of us, which I gotta be honest, seems nuts with the in-vitro evidence. Blah.

Autumn 32 w/CF
 
G

Gracie4

Guest
Thank you for sharing.

How much of a variation do you normally see when performing a PFT? I purchased the spirometer for home use, so I use do ca 25-30 blows before I settle on my average. Depending on my technique, I can have a 10%-30%+ swing. So I try not to get too excited when I read that a new drug may improve a PFT (FEV1) score, for I'm not certain as to if it's considered a real marked improvement.

Does anyone else experience the same swing in results?
 
G

GenH

New member
triples15 said:
Gen, what are you thoughts about how the FDA approval process will go down? I guess specifically in regards to how long those of us with a residual function mutation will wait. I'm hoping that somehow if/when it gets approved for the homozygotes we will be able to get our hands on it. But, I fear it will still be considered off-label and will still be out of reach for most of us, which I gotta be honest, seems nuts with the in-vitro evidence. Blah.

Autumn 32 w/CF
Click to expand...

Autumn, I am not that familiar with the FDA system as I live in Australia, but Vertex have said that they hope to expand the Kalydeco label in 2014. This comment followed information about the other gating and residual function trials- so the info was not specific to residual function. I hope it is approved as soon as possible given the in vitro evidence, but first they need to work out how to classify someone as residual function for the label (eg based on genotype or phenotype or both). Data is expected from these two studies later this year so we will know more then.
 
G

GenH

New member
Gracie4 said:
Thank you for sharing.

How much of a variation do you normally see when performing a PFT? I purchased the spirometer for home use, so I use do ca 25-30 blows before I settle on my average. Depending on my technique, I can have a 10%-30%+ swing. So I try not to get too excited when I read that a new drug may improve a PFT (FEV1) score, for I'm not certain as to if it's considered a real marked improvement.

Does anyone else experience the same swing in results?
Click to expand...

Hello, I have experienced that with the mini wright digitial, but with the pico1 my values have been close together and the highest value has been within 1% of the hospital (about 5 clinic visits so far). Maybe try another device? Do your FEV1 blows at the hospital vary? If they vary there as well, maybe its the technique you're using?
 
K

kyeev

New member
GenH said:
Autumn, I am not that familiar with the FDA system as I live in Australia, but Vertex have said that they hope to expand the Kalydeco label in 2014. This comment followed information about the other gating and residual function trials- so the info was not specific to residual function. I hope it is approved as soon as possible given the in vitro evidence, but first they need to work out how to classify someone as residual function for the label (eg based on genotype or phenotype or both). Data is expected from these two studies later this year so we will know more then.
Click to expand...

Luckily (!?), many of our CF mutations are so rare that it would be impossible to carry out a clinical trial because there wouldn't be enough patients with a specific genotype.
So, I'm hoping in vitro data like this (for other mutations) will be sufficient to allow clinical use.
I don't think there's any other way of trialling it, other than "suck it and see"...
 
N

nitecuento

Guest
The results in the first two graphs are astounding, but it is not completely clear to me if the "Chloride transport (%Normal CFTR)" values, axis of ordinates, was measured in vivo or in vitro. I would tend to think they are chloride sweat values, but is it really so? Are they nasal potentials?
 
G

GenH

New member
nitecuento said:
The results in the first two graphs are astounding, but it is not completely clear to me if the "Chloride transport (%Normal CFTR)" values, axis of ordinates, was measured in vivo or in vitro. I would tend to think they are chloride sweat values, but is it really so? Are they nasal potentials?
Click to expand...

I just checked the wording in the article about gating mutations (Yu et al. 2012) and it says "The impact of the increase in CFTR channel gating by ivacaftor on total chloride transport was assessed in Ussing chamber studies using FRT cells expressing the known CFTR gating mutations" - so it seems it is in vitro data
 
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