1) The "On Par for a Cure" golf tournament for the CFF was May 11th, and was all consuming,
2) Nothing has changed with Brady, he is still holding steady at a level I would call "AWESOME," and I assume that people aren't super interested unless I have something important to say.
3) My head has been a mess. I want to preface this whole entry by saying: I am not a CF expert. I am a stay-at-home mom of a 4 yr. old son with CF. I happen to have a background in Chemistry and have learned a lot on my own about CFTR science. This is all my opinion.
Things are going great for Brady on Kalydeco. What could I possibly have to worry about?
In some ways I am extremely happy. I am on top of the world that Brady has Kalydeco and is doing as well as we had hoped, so why am I still laying awake at night? Why do I feel so fortunate, yet so tortured at the same time? I'm not going to dance around it and try to be politically correct, I'm just going to say it--THERE IS A MUCH LARGER POPULATION OF CFers THAT COULD BENEFIT FROM KALYDECO, BUT DON'T HAVE ACCESS TO IT. Any CF patient who successfully transports any quantity of CFTR to their cell surface would respond to treatment with Kalydeco to some extent. Researchers already know that this group includes:
*ALL gating mutations,
*Most Conductance mutations,
*Some splice mutations.
The fact that the group of Kalydeco responders might soon be expanding is fantastic news! I talk about mutation classes and what that means for CFTR transport in this blog: http://luckycfmom.blogspot.com/2011/11/mutation-matters.html Yet, all of us are painfully aware that Kalydeco has only been approved for G551D ages 6+ and it is extremely difficult or next to impossible to get insurance coverage for this super expensive drug "off-label." Furthermore, there is a growing body of evidence showing that in some cases, Kalydeco has been beneficial for patients who shouldn't theoretically show any response to the drug such as:
1)Heterozygous patients with class 1 and 2 mutations
Theoretically, From what we know about these mutations individually, there should be no CFTR on the cell surface and these patients shouldn't show a response to Kalydeco.
In reality, I know of several cases of patients obtaining a script and coverage for Kalydeco "off-label," trying it, and showing reduction in sweat chloride and improvement in lung function. I think some patients are having some CFTR reach the surface when their two CF mutations interact with one another through a process called Transcomplementation: http://luckycfmom.blogspot.com/2012/03/calling-all-heterozygotes.html
Almost everything you read about the DDF508 response to Kalydeco is that it DOES NOT work for this group. I want to very cautiously put this out there.
Theoretically, there should be no surface CFTR to potentiate. The vast majority of patients showed no significant response.
In reality, a very small subset of DDF508 showed some response to Kalydeco in trials. We are talking about 1 in 112 patients. The scary thing is that they (researchers) have no idea how to identify one of these responders. What makes them different from any other DDF508?? Still, right on the insert in every Kalydeco bottle it states that the drug is "not effective in patients with CF who are homozygous for the F508del mutations in the CFTR gene." Is 1 in 112 patients statistically significant? No. Does that extremely rare DDF508 responder deserve the chance to find out if Kalydeco could help them? Yes.
The thing is, the biochemical reactions that take place within your body are as unique to you as your fingerprint. We know that there is wide variability in the severity of CF, even between siblings or twins with identical genotype and similar environment. There are other factors at play that influence CFTR. I think Peter Mueller from Vertex was on to something amazing when he discussed idea this a few months ago.
http://iom.edu/~/media/Files/Activity%20Files/Research/GenomicBasedResearch/2012-MAR-21/3%20-%20Peter%20Mueller.pdf Take particular note of slides 31-37. Doesn't that just blow your mind? How awesome would it be to receive your own "Trial in a Box" from Vertex to track your body's response to Kalydeco and make a treatment decision based on the results?! **This is not an official trial, or registered with clinicaltrials.gov. This is an idea that is being talked about by those in the know...Vertex is definitely NOT recruiting for this right now. It is just being discussed at a preliminary level. The cooperation of the FDA and insurance industry would be of the utmost importance.
Disclaimer --I just want to clarify that I am not suggesting that Kalydeco would work in every CF patient. There are many CF patients that don't successfully transport any CFTR to the cell surface, and would not respond to treatment. The point that I want to drive home is that: NO ONE KNOWS FOR SURE IF IT WILL WORK IN AN INDIVIDUAL UNTIL IT IS TESTED IN THAT INDIVIDUAL.
Response Guided Therapy
In an ideal world, when a drug like Kalydeco is discovered and found to be safe, people would be free to decide if they want to try it, and see if they feel better, or their sweat chloride drops. If you show a response, then you would remain on the therapy. If you didn't, they would know that you have no surface CFTR and you would stop and wait for the corrector + potentiator combo moving down the pipeline. I mean, wouldn't this be revolutionary! The problem is that this "trial in a box/trial of 1" design is not something that the FDA would look at as a valid statistical measure for approval. That is why it is extremely important that the CF community continue to support the EXPERRT Act, which allows the FDA to bring in disease specialists for rare conditions like CF to best determine the endpoints for trials, etc... The CF Foundation is truly blazing the trail toward a new generation of individualized, gene based medicine. You can imagine that there are a few "norms" that we are going to have to challenge along the way. Both Vertex and the CFF are legally bound to stay out of any off-label use because they are focued on obtaining wider regulatory approval in the U.S. and of course for our friends in Europe and Australia. Waiting sucks. I'm sure that Vertex would love nothing more than to fill thousands more Kalydeco orders and the CFF would love to see its community live longer and feel better. Unfortunately, they have to play by the rules.
I can't underestimate the importance of seeing the EXPERRT Act pass and become law because it would allow us to slightly change the rules and persue more individualized approaches to treatment. The repercussions for CF patients could be phenomenal. Visit the CFF's advocacy tookit to read about the EXPERRT Act, and quickly and easily email your elected officials asking for their support. We need to educate the FDA about the new ways we are individualizing treatment for CF patients and this will allow us to be heard! Personalize your letter for the greatest impact! http://www.cff.org/GetInvolved/Advocate/AdvocacyToolkit/EXPERRTAct/
Brady is part of the National CF Registry and we have documented in detail the benefits of Kalydeco through both office exams and lab work. Every off-label approval and documented success of Kalydeco will tilt the odds a little more in our favor for additional insurance companies to approve it for others off-label. Remember when Pulmozyme was first approved by the FDA? It was only trialed in kids age 6 and older. Of course, Dr.'s soon saw its benefits and began prescribing to younger patients. At first, the insurance industry pushed back, but after seeing it routinely prescribed and accepted by other insurance companies, everyone eventually just began covering it for younger kids also--OFF-LABEL! Even insurance companies can see that PREVENTING problems in CF is cheaper than FIXING problems once they have already occured and caused potentially permanent damage. I realize that Kalydeco is dangerously high priced. It raises an automatic red flag for insurance companies. Our insurance told us that it happens for anything costing over $10K per month in their system. They automatically required the "letter of medical necessity" from Brady's Dr. and a "pre-authorization." I live with constant fear that our insurance company will change their mind about covering Kalydeco for Brady, so we have been seeing the Dr. frequently, doing lots of lab work, and making sure there is NO DOUBT that it is working wonders for him. I order his 5th bottle on Monday! I can hardly believe it!
Back to why I can't sleep
The image from Breck's thoughtful and well-written blog just after Kalydeco was approved has never left my mind. http://bennettgamel.blogspot.com/2012/01/will-helicopters-return-in-time-for-us.html Everyone waiting...stranded on that rooftop with the floodwaters rising around them. She said it so brilliantly. This is how I feel as I see how Kalydeco has positively affected Brady, and also having the knowledge that it could be helping many more.
I hope everyone writes in to their representatives in support of the EXPERRT ACT! I want to see the day when the "trial in a box" is more than an idea...it is a reality! So what do I do now? Since my family has the nourishment it needs, we can work to build shelters for the others, care for them in their weakest hours, and relentlessly keep the rescue fire burning, in the hopes of attracting a less idiotic helicopter pilot. I may not be able to share my nourishment, but I can share my energy and love. In Breck's version, my family flies away on the helicopter to safety, leaving the rest behind. In my version, and in my heart, I will never leave the CF Community. The rescue fire will never go out on my watch.