5 weeks of Kalydeco

So I have now been on Kalydeco for 5 weeks. For those who don't know me, I do NOT have G551D nor do I have any sort of gating mutation.

That being said, as many of you know, there was a small subset of patients with DDF508 in the Phase III Kalydeco study that had a very large increase in FEV1 with the drug. Genes don't tell the whole story with this drug - as you see with many CF patients, their genes don't predict how healthy/unhealthy they are. Siblings, with the exact same CF mutations, have varying CF outcomes.

Diet, exercise, modifier genes all have an impact on how CFTR functions.

So I wanted to try Kalydeco. Keep in mind, as I started the drug, I was diagnosed with CFRD. Meaning I have had out of control blood sugars that are artificially suppressing my lung function - most likely over the past 1.5 - 2 years I think (I have been having false negative OGTT results).

Upon starting Kalydeco, my FEV1 was approximately 2.3L, which is around 81% (waaaaaaay down from my normal of mid 90s, I know. It's been a rough year for me).

2 weeks in to taking Kalydeco, using my home FEV1 monitor, my FEV1 went up to 2.56. This was prior to taking any diabetes medication or doing any other changes in my diet, exercise or medication routine.

That's an 11% increase in FEV1. And I felt it.

I could laugh without coughing my brains out for the first time in years.

(EDITED TO ADD:I did PFTs on Monday, April 9 at my clinic and then came home to compare to my home meter - the FEV1's were 0.03 apart. So although I didn't have the opportunity to take a look at my FEV1 on the same machine a few weeks ago because I didn't have a clinic appointment, I do believe my home machine correlates pretty closely to my clinic machine.)



Unfortunately I got bad allergies from really really crazy winds that were blowing around that turned me in to an inflammation nightmare. That, coupled with experimenting with my blood sugar log (I wanted to see what would happen with my sugars when I ate a "treat" aka sugary stuff, vs normal stuff vs. healthy stuff) I think really set me back. I blew about 2.32L last Tuesday (at about 4.5 weeks).

Due to diabetes, they did my first urinalysis and it came back that I was super dehydrated (they were checking for me spilling protein in my urine - big sign of uncontrolled sugars) - and of course DUH! Dehydration wasn't helping my lungs either. This was prior to starting insulin as well - no changes in medications until 4/11 where a basal insulin was added.

So bottom line is, I don't have G551D and I had no expectation of having miraculous, mind-blowing FEV1 results with Kalydeco. But I do know that one's genes aren't the only story with CFTR function, so I was bound and determined to get my hands on this drug off label.

So we shall see where my lung journey will go - I am anticipating that my lungs will feel a bit better with some  insulin on board. But any change in FEV1 from here on out can be attributed to better CFRD control, not necessarily Kalydeco. So I a grateful I had a handful of weeks to change nothing about my care other than Kalydeco to see the true changes.

I will continue to keep you all posted.

But there is no doubt in my mind that Kalydeco had some impact......

........and I'm so grateful that my country doesn't have nationalized healthcare or socialized medicine so I could get a hold of the drug off label and my government couldn't restrict me. I'm willing to bet getting a hold of Kaly in Australia, England and Canada for non-G551D patients will be nearly impossible. I already know of more than a dozen here in the States, and I'm sure there are more.

Yes, it's my blog, and I can make a political statement if I want.


"A government big enough to give you everything you want, is also big enough to take it away." 
-Thomas Jefferson, 3rd President of the United States and principle author of the Declaration of Independence 

Day 2 - Kalydeco

Well, suffice it to say that I feel a bit like I'm flashing back to Fall 2006, about 5 1/2 years ago, when I first started taking NAC. (http://noexcusesnoexcuses.blogspot.com/2008/08/nac.html)

It's true, we look for little signs of medication working or for side effects particularly right when we start something new. I took my first dose of Kalydeco right before bed on 3/9 Friday. Here is what I observed:

• Prior to starting Kalydeco, I had been a bit non-compliant with my green smoothies and felt quite a bit more tight and non-moving mucus-y in my right middle lobe. I would cough but nothing would come up - but I could tell it was there. My FEV1 on 3/5 at clinic was 80%

• When I woke up yesterday (3/10) AM, the first thing I noticed was how clear my sinuses felt. I could feel air moving in my sinuses where I feel like I've never felt air move before. Like up above my eyebrows - it was almost distracting because it was so different and weird

• I coughed up pretty watery, much thinner than what I had the past few day's mucus. My right middle lobe felt much clearer

• I have kind of avoided exercising the past few weeks because it was so exhausting to cough so much - but exercising yesterday was much easier and I could breathe deeper in my right middle lobe. I coughed while exercising but it was mostly a dry cough

• Today I don't notice as much air flowing through my sinuses, but it's possible that I'm used to it or it was just a fluke yesterday. Not sure

• I for sure have a plug stuck in my right middle lobe and it's a bit harder for me to breathe in my right lobe today. I am going to try to go for a run later today to cough it up (that usually does the trick) - it will be cool to see how my endurance is

• I had another feminine side effect that normally I would post here because I'm comfortable posting anything - but I realize that all my readers might not be comfortable reading all I feel to share. Ha. So if you're curious, drop me an email or a PM and I'll fill you in :)

So all in all, some changes that I am cautiously optimistic about. It may be complete placebo effect, but that's fine with me - I feel good, whatever the cause. 

I'll continue to keep you guys posted

1st Kalydeco dose

I was very fortunate and blessed to get my 1st Kalydeco dose in the mail today.

Luckily my doc was willing to give it a try, even though I don't have G551D (I have DF508 and Di507). And my insurance covered Kaly for a really reasonable co-pay.

I'm really not expecting it to do much, but I figured it most likely won't hurt me so I should just give it a shot.

There are so many things that can influence how genes are expressed, such as modifier genes, exercise (Stanford states that exercising actually increases CFTR function) and the foods we eat. So I think our CF genes don't tell the whole story - another reason why just trying Kaly is a good idea in my mind.

I look forward to keeping you all posted on my progress or lack thereof over the next month(s).

Update so far is that I took my 1st Kaly at around 9pm with my dear friend and parents watching me over video chat.

Bottom's up!

According to Vertex: "In recombinant cells VX-770 increased CFTR channel open probability (P(o)) in both the F508del processing mutation and the G551D gating mutation."

http://www.ncbi.nlm.nih.gov/pubmed/19846789

From Annals of Human Genetics, 2003, by Rowntree et al,:

"Measurements of Cl- conductase of intestine and respiratory tissues of DF508 homozygote CF patients suggest, in vivo, that at least some DF508 CFTR can reach the plasma membrane"

http://www.colorado.edu/MCDB/MCDB4600/1ReviewPhenotype.pdf