Kalydeco is the first drug available that targets the underlying cause of CF. All the other therapies available for CF treat the symptoms of the disease. So this pill is a real breakthrough! Kalydeco improves the faulty gene and its protein product, CFTR. As we know Kalydeco, is only approved for use on individuals who have the G551D mutation. CFers who have the G551D mutation have the defective protein in the right place on the cell surface but it does not function correctly. Instead, it acts as a locked gate which prevents the proper flow of salt and fluid in and out of the cell. So what Kalydeco does is it unlocks the gate and restores the function of the CFTR protein. This allows for proper flow of salt and fluids on the surface of the lungs. By allowing the proper flow of salt and fluid, the mucus in the lungs is less sticky and thin.
Kalydeco is not a cure in any means but it is something that will prolong life for years to come in my opinion. In fact, the pill has shown to improve lung function, lower sweat chloride levels which in turn has lowered sweat test results, and has also helped individuals gain weight. Basically, the people who have G551D mutation and are taking Kalydeco are living what I would call a “CF free symptom” life or mostly symptom free life. But the thing is that Kalydeco has only been found effective so far to help G551D mutation which is about 4% of the CF population or slightly over 1,000 CFers.
So what about all the rest of us who do not have a G551D mutation? Well there is hope and it is really exciting to be reading about the research that Vertex has been doing. For most of us in the CF community we have at least one copy of mutation DF508 and that is where a lot of the research is being focused on the DF508 gene more so individuals who have two copies of DF508. The problem with the DF508 mutation is that the defective protein is not at the correct place on the cell surface and the gate is locked for the proper flow of the salt and fluid in and out of the cell. Whereas the G551D mutation has the defective protein, CFTR in the right location but the gate is locked. So in order for Kalydeco to work on individuals who have the DF508 mutation the cell needs to move the CFTR to the cell surface and open the gate. We know that Kalydeco can open the gate but Vertex is still working on getting the CFTR up to the cell surface. In fact, they have released some exciting data on moving the CFTR to the cell surface with a pill called VX-661 and VX-809 and then opening the gate with Kalydeco. Here is the link for the news release for the the results of VX-661 and Kalydeco.
It looks like there will be a more clinical trials for both VX-661 and VX-809 and Kalydeco. In the VX-661 study it has shown to have improved lung function by a whopping 9% and lowered sweat chloride levels in individuals who have two mutations of DF508 which is the most common CF mutation. This is really really exciting and looks like the magical pill(s) will be looking for FDA approval in the near future. I have heard as soon as 2014 that Vertex will be submitting and looking for FDA approval on VX-661 and or VX-809 and Kalydeco for individuals who have two copies of DF508. I cannot wait for this day!!!
Ok, but wait there are still a good amount of CFers who do not have two copies of DF508. In fact, I am in that boat. But I truly believe if this VX-661 and Kalydeco combination will work on two copies of DF508 then it will work on people who have just one copy. They may have to play around with the dosage and strength to get a “perfect” mix but it is going to happen, I know it is!
But my main reason for writing this blog today is to talk about some exciting things I have read about Kalydeco and possibly helping other mutations. I became aware of this through a forum I read and leave comments on. While scrolling through a couple forum posts I found one that interested me big time. It had the wording of Kalydeco and 3849+10kbC->T. I decided I better read this because I have one gene mutation of DF508 and the other is 3849+10kbC->T. In fact I even found a Facebook group that has members who have my same gene copies, WOO HOO! When I started reading this forum and Facebook posting I couldn’t believe what I was reading. I think this was one of the greatest finds I have ever found online and I am so excited that all my time and effort on forums is going to help me possibly. As Maria says, I am addicted to anything CF related online and I guess this time it really is going to pay off.
So here is what I have been spending a lot of my time reading and not blogging lately. But I guess I have good reason! I honestly, thought all along that Kalydeco could help me and my one gene 3849+10kbC-> because this gene does produce functional CFTR at the cell surface but the quantity of CFTR is affected. I even asked my doctor when Kalydeco first made it to the market if it could help me or other genes. His answer was that is the big question. Well I think I am finding out the answer to my question and I CANNOT BELIEVE what I am reading. Apparently, there is an actual research study that is being conducted at a Denver Colorado hospital testing the effect of Kalydeco (aka Ivacaftor) on lung function in subjects with CF that have residual CFTR function. My 3849+10kbC->T gene is in this group.
On the facebook page that I belong to, I was reading that Kalydeco is really helping people with my CF combination. There are a few people who are in the study and another mom who has traveled from Italy to the USA to get her son on Kalydeco. I honestly could not believe what I was reading. The mother from Italy had said that her son’s FEV1 increased by 7 or 8 points and he was able to gain a good amount of weight. I have also read that some people in the Denver study have also seen their PFT improve while on Kalydeco in the study. All of this is really hitting home for me that the magical pill is within reach very very soon!
There are also other mutations that the Denver study is enrolling. In fact here is a list of the mutations that they are testing Kalydeco on and some of you I know who read this blog have a copy of one of these gene mutations. CF Stinks I know you can participate in this study!!!
CFTR Mutations associated with residual CFTR function or defective mRNA splicing include the following:
R117H, E56K, P67L, D110E, D110H, R117C, R347H, R352Q, A455E, D579G, S945L, L206W, R1070W, F1074L, D1152H, S1235R, D1270N, 2789+5G->A, 3849+10kbC->T, 3272-26A->G, 711+5G->A, 3120G->A, 1811+1.6kbA->G, 711+3A->G, 1898+3A->G, 1898+1G->A, 1717-1G->A, 1717-8G->A, 1342-2A->C, 405+3A->C, 1716G/A 1811+1G->C, 1898+5G->T, 3850-3T->G, IVS14b+5G->A, 1898+1G->T, 4005+2T->C, 621+3A->G, 621+1G->T
This link contains the clinical trial for the experimental Kalydeco below. http://clinicaltrials.gov/ct2/show/NCT01685801
So to summarize this very long post it looks like there will be a magical pill possibly for residual CFTR function. The results of the Denver study will be posted in September 2013 which is very soon. But if anyone wants to enroll in the Denver study they are still accepting patients. It really is to bad that they are only offering this study in Denver. But I have heard that Vertex Pharmaceutical will pay for your expenses to attend this study.
I will leave with you a to BE CONTINUED blog because I still have not said if I will be participating in this study. I also have some other information on this study to summarize but I figured I better end it here. So for anyone who is interested in this study or would like to know if I will be participating in this study let me know if you would like Part 2.
Alayna in her high chair for the first time!