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VLC 2013 Science Update

Tuesday, March 26, 2013

{EDIT: I apologize in advance that there is a lot of technical information in this post.  I have tried to make it as easy to understand as possible.  But if I can clarify something, please let me know.  Also, if you were at the VLC meeting and heard this talk and noticed I have an error, please let me know, as well!}

I learned a ton during the Cystic Fibrosis Foundation's Volunteer Leadership Conference I recently attended.  So, I thought I'd share what I learned in several smaller blogposts rather than in one large one.  Here's what I learned...

1.) The CFF believes Kalydeco may help all of us and up to 95% of those with CF could benefit within 4 years!

Bob Beall started out his talk to our group by sharing a few really encouraging words.  One quote I loved that he said was: “our vision has never been clearer or more focused...It’s not when we get there but what’s it going to be like when we do.”

Below are several slides shown as a part of the update on the Science presentation by Dr. Preston Campbell...

This slide shows the benefit of Kalydeco (also known as "ivacaftor").  As you can see, Kalydeco shows huge improvement over the current medications available for improving lung function.


To me, this slide is probably the most impressive slide of all the Conference.  This is what the CFF predicts for the expansion and benefits of the current CFTR Modulation drugs.  Let me explain it...
2013 lists 4% of those with Cystic Fibrosis (mainly those with the mutation G551D and the like) who are currently benefiting from Kalydeco.  This number is expected to increase to about 8% by 2014 because the Cystic Fibrosis Foundation is currently looking for other mutations who might benefit from Kalydeco.  This number has the potential to go up to 65% by 2015 because it is hoped that the VX-809 drug will be available at that point and will be effective when given along with Kalydeco to those with double Delta F508 mutations.  By 2017, the CFF hopes to increase this number to 95%.  That's right, the CFF is predicting that by 2017, up to 95% of the Cystic Fibrosis population may benefit from Kalydeco as the additional 30% of the population which has Delta F508 + one other mutation will also be able see benefits from Kalydeco and VX-809.

Based on this information, I am assuming that it is expected that, by 2015, Phase III trials will end for VX-809 and it will be placed on the market...and that, for those with with Delta F508 and another mutation, they will see their medication succeed through Phase II and Phase III trials by 2017.

For Bennett, this means, there is a very real possibility that he will see a reasonably effective medication benefitting him by 2017.  SO EXCITING!!!


This slide shows The Effect of a Potentiator and Corrector on CFTR Activity in the lab.  As you can see,  the G551D mutation demonstrates less than 10% CFTR activity in vitro (this is why those who have it G551D, along with another CF mutation, have Cystic Fibrosis - CFTR activity is very important to the body).  The slide also shows, however, when given Kalydeco, those with G551D see significant improvement in the CFTR activity as the cells in the lab show CFTR activity reaches 50%.

If we look at the Delta F508 mutation, we see that VX-809 by itself provides 20% CFTR activity.  While that is some activity, it is still too low to show significant improvement in the disease.  But, if Kalydeco is added to the V-809, we see about 35% CFTR activity.  This is better, but still not the improvement that those with G551D and Kalydeco see.

The goal is that the body see 50% CFTR Activity in order not to show signs of Cystic Fibrosis.  The CFF believes that if we can give patients with Delta F508 the medications VX-809, Kalydeco and one other effective drug (here its called VRT-XXXXXXX), patients should be able to get 50% activity.  The drug VRT-XXXXXXX has not been identified yet.  This is why it is listed as this.  But the CFF is working hard to identify this drug.

The point is that we're close...but not there yet.  The Cystic Fibrosis Foundation will continue working with the pharmaceutical companies to identify the drug that should help bring CFTR activity in the Delta F508 mutation up to 50% like we see in the G551D mutations.

For those who haven't followed the big news in the world of CF, it was announced at the end of last month that Vertex is beginning Phase III trials for the combination if drugs Kalydeco and VX-809 for those who have two copies of DF508 (about 50% of the CF population).  As evidenced in the slide above, this looks very promising in the lab for those with Delta F508.  We hope that Phase III trials will meet or accede our expectations.

For those like Bennett who have have one copy of DF508 and a copy of another CF mutation (which is   40% of the Cystic Fibrosis population), Vertex is just now beginning Phase II trials on the combination drugs Kalydeco and VX-661.  This is a very important milestone for those with one Delta F508 mutation, including Bennett.

But the CFF is not stopping there.  They want to make sure all who can benefit from Kalydeco can.  The CFF is working to identify more genetic mutations who can benefit: there are already ongoing efforts to identify the next generation of DeltaF508 CFTR correctors.

In addition, the CFF is looking in to how 
Gentamicin may work for those who have "stop-codon" mutations.  They said they don't know if it will be good enough for the stop codon mutations but they are going to find out.

For those with Bennett's mutation (621+1G>T), I had originally thought that this mutation of Bennett's was a "premature stop-codon."  However, Dr. Preston Campbell did an great job helping me understand that it's, in fact, not.  Instead, it's a "missense mutation."  (Therefore, gentamicin should not work on Bennett's mutation.)

Dr. Campbell said that it is unknown whether or not 621+1G>T is responsive to Kalydeco and "testing in the laboratory will be difficult due to technical difficulties" but "they will soon sorting this out."  

Other good news I heard at the conference is that those with CF who are pancreatic sufficient may have residual CFTR function.  Not only does this mean their disease is likely less severe but it also may mean they do not need as much benefit from a drug to see significant improvement in their disease.  Although this is not Bennett's situation, it makes me very hopeful for those who are pancreatic sufficient as they may not need much in the way of effectiveness from a drug to see significant benefits.

The question remains, of course, for the 5% of those with CF who have what is called “X” mutations.  These mutations have not found their miracle drug yet.  The Cystic Fibrosis Foundation continued to say over and over and over again during the conference that they would not stop until 100% of those with Cystic Fibrosis are cured.  

Unfortunately, I did not hear of any trials for drugs to help those with these mutation as they are incredibly rare.  But that does not mean that the CFF does not know about them or doesn't want to help.  They are just more difficult and the CFF is working as quickly as a possible to get medications to help them as well.


The great thing is that the CF Foundation is it is working very hard for a cure.  Just this year alone, the CF Foundation will spend $120 million this year on its medical program (research and efforts to find a cure) which is funded mainly with private funds (most from our Great Strides efforts) in addition to the royalties the CF Foundation gets from Kalydeco.

Bob Beall shared that the Foundation has taken the money they would get from royalties from Kalydeco and already sold it to a broker (he said they simply did not want to waste time).  This broker has given this money to the Foundation which the CFF has already turned around and used to invest in research for the next generation of drugs.  Bob shared something to the effect: "we don't have time to sit around and wait for the money to build up in an account so we can reinvest it in research.  We needed to do it now."  

I have more updates to include but these might just be my most exciting of all my updates for it shows the CF Foundation is absolutely making progress and Bennett may end up benefiting from a significantly effective drug within the next 4 years!!  Yaaaaahoooo!!

5 Responses to “VLC 2013 Science Update”

  1. Wow, this is so exciting! Thanks for sharing!

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    1. Thanks, Dana!! I thought it was super exciting too! Almost too-hard-to-believe exciting!! :)

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  2. Thanks for sharing this, Breck! Do you mind if I share it on my blog, or link up to your blog. (Not sure how to do this exactly.) But super excited to hear this. If you read my blog, you will understand God's perfect timing in getting to read your blog today. Needed a bit of hope and light tonight! =)

    Hope and pray that you are all doing well!

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    1. Tiffany, absolutely you can share this post or link to your blog! I read about Rachel's sobering question about whether CF will kill her. How difficult to hear, as a mother! I dread the day when Bennett asks me something similar and I have no choice but to be honest. Let's pray both our kiddos will benefit from these new medications soon...before they really understand the gravity of this disease. we are SO close to a cure, girl! Hang in there!! :)

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  3. "Dr. Campbell said that it is unknown whether or not 621+1G>T is responsive to Kalydeco and "testing in the laboratory will be difficult due to technical difficulties" but "they will soon sorting this out."

    I would assume that "technical difficulties" here means "difficulty in gathering a large enough sample".
    If so, they just have to know where to look for.

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