Saturday, February 4, 2012

Hiking Off-label

I’ve been visualizing this for years.  From the moment I first heard about VX-770(4 years ago), there have been lots of naysayers.  Predicting it won’t work like they say, it will fail in clinical trials, it is too good to be true.  I’ve tried to remain positive and focus on the possibility that the vision might be true.  As the years passed and the trial data came out, my vision took on color and detail.  I started envisioning the day that Brady wouldn’t have to wake up to an hour of treatments.  The day when my heart might not skip a beat because I hear someone in the store cough.  The day when I have the luxury to worry about regular things, like how popular he is in school, or how good he is at sports…because I don’t have to worry about his simple ability to breathe.  I’ve always believed that if Brady could get this drug before he has sustained significant permanent lung damage, that he might truly be spared a lifetime of breathing and airway clearance treatments.  A second chance. 

It is difficult to describe where my head has been since last Tuesday’s big announcement of FDA approval of Kalydeco.  The initial phase I will call BREAKDOWN: A huge wave of emotion.  Unbelievable.  I cried for hours that day.  I mean, I sobbed in a pile on the ground.  I cried in the bath tub.  I cried at the coffee shop.  I think I scared some kids because I cried at the park.  A weird cry too.  I mean, I know I had a huge smile on my face as the tears streamed uncontrollably.  I emailed Brady’s Dr. that morning and heard back from him within the hour.  This is exactly what he said in regard to getting Kalydeco for Brady off-label,

“Pure speculation, based on prior drugs through the years (though obviously this is a unique and groundbreaking drug, so precedents may not be perfectly applicable:

1. Likely will be a several week delay until the supply is actually available. Don't know if this will initially be available through typical retail pharmacies, or restricted initially to CF pharmacy and/or a few select outlets.

2. Since off label use is always a huge question with any new drug, especially an expensive one, I would imagine the process for kids like Brady will be a "one foot in front of the other" process. We would write a script, submit it to pharmacy, expect rejection initially by third party payor based on age, then write letter(s) documenting the appropriateness of off-label use. I would anticipate that the process would take several months, but that enough pressure will build nationally that third party payors will relent, especially when age is the only off-label parameter, and age isn't that far off (for example, not an infant). But of course I am totally speculating, as I don't even know the cost of the drug yet (do you?).

3. Meanwhile, I would anticipate CFF producing a position paper supporting off label use, at least for age parameter. This should come out fast and should help a lot (again, I am purely speculating---I have no insider information that such a paper is pending or even being contemplated at present, but I would be shocked if it isn't already in rough draft form).”

I think the important thing to remember is that there is NO PRECEDENT for this.  We have tried and succeeded at getting many other drugs for Brady off-label in the past, like Pulmozyme for Brady at age 6 mo.(for which it is NOT approved).  We understand that Kalydeco is different because it is a new type of drug and one of the most expensive ever marketed in the United States. BUT… How many CF parents out there would walk across hot coals right now to get a similar drug to their child?  I’m so determined to get this drug to Brady because every day that he lives without it is a day he might colonize some nasty bug, do further damage to his pancreas and liver, or catch a virus that could lead to permanent lung damage.  I’m sure I don’t have to explain to other CF parents how every single time we go to clinic we are nervous about what the culture is going to say...what the chest x-ray might reveal…what his bloodwork might indicate… We have been extremely lucky that he still has clean cultures for now, and has very good lung health.  Let me preface this next part by saying this: I realize Brady is not going to die if he doesn’t get the drug right away.  I realize that even if we had to sit around and just wait for him to turn 6 years old(a year and a half from now), he would be fine, excellent even!  With the exception of his sinuses, he has enjoyed a tremendously healthy childhood so far.  I’m sure that some people look at my reaction to the FDA approval and feel like I’m jumping the gun by trying to get the drug for Brady right now.  I want to explain why I’m so utterly convinced it will be safe for him and is just as crucially important for him now as anyone with G551D. 

1)      We, and Brady’s Dr., believe the 150 mg./twice daily dosage is safe and appropriate for him.  All trial participants, whether they were skinny 6 yr. old girls or grown adult men received the same dose.  Also, the full prescribing information for Kalydeco(available on Vertex’s website), describes that participants beginning the drug should monitor the drug’s effect on their bloodwork every 3 months for the first year and annually after that.  We have already discussed this with Brady’s Dr. who will be monitoring Brady’s bloodwork even more often than that!  If the dosage would happen to be too high, which we don’t believe is true, we will be watching him like a hawk and closely monitoring how his organs are handling and metabolizing the drug.  The prescribing info says to space doses more widely, or even drop down to once a day dosing for cases of elevating liver enzymes to more than 5x over normal levels.  People seem to assume we are being reckless by trying to put him on this drug when it hasn’t been trialed in children his age.  Some parents also don’t believe in putting their infant on Pulmozyme even before lung problems develop (which we did, OFF LABEL).  I guess we will just have to agree to disagree.  We also give Brady tons of nutritional supplements and he sees a naturopath in addition to his CF specialist.   Doing what everyone else is doing has never really been our biggest concern.  We have always been extremely aggressive with Brady’s preventative care because we want to keep him as healthy as possible.  We would never be pushing for this if I believed it wasn’t going to be safe for him. 

2)      We believe living with non-functional CFTR is a way bigger risk than the taking the drug “off-label.”  I think we can all agree that living with cystic fibrosis is dangerous.  Patients lose an average of 1-2% lung function for every year that they are alive.  There is constant risk of developing cystic fibrosis related diabetes, liver problems, bacterial colonization, or permanent damage from a nasty virus.  I’ve been a little bit surprised by some people who act like TIME is a luxury that we enjoy here in the CF Community.  People have died waiting for this drug and others will die waiting for the combo.  Every day waiting is too damn long.  I mean, let’s say that we decide to just wait and this is the year that Brady colonizes pseudo and ends up in the hospital for his first tune-up.  Is it the end of the world?  No.  I know he is still young and going to be fine.  Does that mean I don’t want to prevent it from happening and try to get him on this drug while his lungs are as pristine as possible?  HELL YES!  The whole key to being able to actually REPLACE lots of your current treatments with Kalydeco is to get the drug while your lungs are still very healthy.  As we are seeing with the adults who have been taking the drug for a little over two years now, some have dropped many of their treatments…others haven’t/can’t.  I want to give Brady the chance to live the rest of his life without those treatments and if we intervene NOW, we feel pretty good about his chances!  His chances will probably still be very good when he turns 6, but we have absolutely no way of telling what the next 18 months might bring.  CF can surprise you when you least expect it.

3)      Brady takes now, or at least initially started, almost every single one of his medicines OFF-LABEL!  Any newish drug (let’s say out in the last 10 years) is not going to have been tested for its benefit and FDA approved for, let’s say, a 3 year old with cystic fibrosis!  Brady began Pulmozyme at 6 months of age off-label (it has only been trialed in ages 1+).  He began Hypertonic saline off-label (the ISIS trial was going on when he started) at age 20 months.  He has been taking ursodiol for CF related liver complications off-label since 4 months old.  He has never been diagnosed with asthma, but takes Singulair off label.  He takes Prevacid to help his enzymes work better.  Not an FDA approved use people--Off-label!  While I understand that this is a problem we will likely be facing with our insurance coverage, I just want to illustrate that the fact that it is off-label means crap to me!   Honestly, the only meds of his that are on the FDA label for treatment of a young child with CF are the enzymes and the vitamins!  This leads me to my last point.

4)      We like to hike off the main trail.  Brock, Brady and I decided to take a hike this morning.  We are sort of on vacation right now in Arizona.  We are staying near the White Tank Mountain Regional Preserve and there are miles of hiking trails through the Sonoran Desert.  We parked at the trail head, but then almost immediately “went rogue” and ventured off the trail system to blaze a path of our own.  This is the way we always do it.  As we stumbled along the rough rocky terrain I couldn’t help but notice both the pros and cons of venturing off the main trail. 

Cons: You are a lot more likely to see a rattlesnake, twist your ankle, step on or simply get too close to a cactus, fall down, and scratch up your legs.  If anything does go wrong, you are further from help. 

Pros: You are a lot more likely to see a lizard, jack rabbit, or ground squirrel (which is why we are there as far as Brady is concerned).  You are more likely to find the rare cactus listed in your cactus field guide that you have been searching for.  The main trail doesn’t lead up to the little ridge with the best vista of the valley…thousands of saguaros and the mountains in the distance, so you have to go “off-label” to get there.  I guess what I’m trying to say is that today, we went for a hike and caught a lizard with our “lizard catcher”(Tupperware).  We hiked up to the best view in the whole area, and we all three came home with a few cactus spines in our butts…but it was worth it.  Brady has been prancing around all day singing this song from one of his Sesame Street videos, “You can do it, you’re not too small.  Don’t give up, even if you fall.  You can do it, you can answer the call, but you’ll never ever know if you don’t try at all.”


  1. Hi Rebecca, I am Jo here, mum of 14 yo girl wcf - df508, so we are still in waiting phase. We are based in Uk, originally from India. When I read this and other blogs I felt that these are exactly my feelings. Also I found this blog very informative, in the sense the various meds and clinical trials you mentioned. Our medical system is much different than that in US, Also there are very few clinical trials going here - also most of them are for adults. Can I ask you what off label means? Is it a clinical trials medicine? Do they allow child to take part in clinical trials below the required age?
    As my daughter will be 15 in couple of months, I would like to know whether any adult trial will be of any use.
    I would grateful if you could write back to me. Thanks.

    1. Jo-Kalydeco has only been tested in clinical trials in patients with the G551D mutation aged 6 and older. When the FDA approved this drug for the market, they indicated that the approved use is for patients over 6. Because Brady is under 6, his use of this drug is considered "off-label." There is a Kalydeco trial for children with any gating mutation(including G551D)beginning this summer. Since Brady is already taking the medicine, he will not be participating in this trial. There are more clincal trial upcoming for DF508 patients here in the U.S. with similar types of drugs to the one I mention here. Not certain about upcoming European trials. Sorry! This drug, Kalydeco, has already applied for EMA approval though, and is expected to be available in Europe in a few months or even sooner!