Kalydeco and Class IV Mutations

[triples15]

Looks like S945L has 5-10% function without any medications. Was your sweat test a little lower than most CFs? You are right, Kalydeco potentiates your mutation significantly. It looks like it restores about 75% of normal CFTR function. This is one of the best relative % responses on the graph. To put this in perspective, G551D gets to 50%. I would use this data asap to convince your doctor! Also the fact that vertex are studying it in a trial with Kalydeco monotherapy means that vertex believe it may be helped.

Wow, thank you so much for looking at that for me! I really really appreciate it. You definitely helped as I had not been able to glean that much from reading it myself! That sounds pretty darn promising for me! I will definitely continue trying to get my doc to prescribe it for me. It really frustrates me that he will not at least try. I guess I don't understand.......what's the worst that could happen, insurance denies it? So what did it hurt to try? Ugh. They just tell me that they have tried to prescribe it for a couple other patients off label and were denied so they're not gonna do it. Hmmmm....

My first couple sweat tests (non-accredited center) were in the borderline range but I don't know the exact numbers. The sweat test that earned me the diagnosis (at an accredited center) was 82. I'm 32 now and that 82 was at 3 months old.

Thanks again! I'll keep you posted on the situation with my doc!

Autumn

 

[triples15]

Yep, Triples15, looks like you're cured!
You just won the Kalydeco lottery. Lucky sod!

Thanks kyeev, this made me laugh but at the same time gave me goosebumps! I'm definitely excited and hopeful but at the same time am trying to remain very guarded. Now if I could just get my hands on the darn drug we could find out how accurate you are!!

Autumn

 

[lifeisgood729]

Autumn,

I also have a mutation with residual function, and my doctor was supportive of writing a prescription for me for off label use. We submitted to the insurance company, and they denied me twice, so I took it to the state appeals level. Using scientific evidence like those graphs, I built an argument that although it isn't approved for my mutation (yet) it is highly likely that kalydeco will be effective for me. In addition to the scientific evidence, I emphasized the information about the Denver trial. There is no way Vertex would invest millions in a trial including our mutations if they didn't believe there was a strong likelihood of success. If you look up the patent info for ivacaftor, you might even find that your mutation is included in the patent. Again, they wouldn't bother to patent the drug for those mutations if they didn't believe that someday the drug would treat them.

A few days ago, I got a letter saying that the independent reviewer agrees with me, and my insurance company has to pay for my prescription. In a few days, I'll be receiving my first shipment!

It's really sad that your doctor is so resistant. The graph alone should be sufficient evidence in the case of your mutation, but if that's not enough to convince them to give it a try, there is plenty of other information out there to build a case. If you can hand him all the evidence and all he has to do is write one letter, maybe you can change his mind.

Keep pushing!

Martha

Wow, thank you so much for looking at that for me! I really really appreciate it. You definitely helped as I had not been able to glean that much from reading it myself! That sounds pretty darn promising for me! I will definitely continue trying to get my doc to prescribe it for me. It really frustrates me that he will not at least try. I guess I don't understand.......what's the worst that could happen, insurance denies it? So what did it hurt to try? Ugh. They just tell me that they have tried to prescribe it for a couple other patients off label and were denied so they're not gonna do it. Hmmmm....

My first couple sweat tests (non-accredited center) were in the borderline range but I don't know the exact numbers. The sweat test that earned me the diagnosis (at an accredited center) was 82. I'm 32 now and that 82 was at 3 months old.

Thanks again! I'll keep you posted on the situation with my doc!

Autumn

 

[triples15]

Autumn,

I also have a mutation with residual function, and my doctor was supportive of writing a prescription for me for off label use. We submitted to the insurance company, and they denied me twice, so I took it to the state appeals level. Using scientific evidence like those graphs, I built an argument that although it isn't approved for my mutation (yet) it is highly likely that kalydeco will be effective for me. In addition to the scientific evidence, I emphasized the information about the Denver trial. There is no way Vertex would invest millions in a trial including our mutations if they didn't believe there was a strong likelihood of success. If you look up the patent info for ivacaftor, you might even find that your mutation is included in the patent. Again, they wouldn't bother to patent the drug for those mutations if they didn't believe that someday the drug would treat them.

A few days ago, I got a letter saying that the independent reviewer agrees with me, and my insurance company has to pay for my prescription. In a few days, I'll be receiving my first shipment!

It's really sad that your doctor is so resistant. The graph alone should be sufficient evidence in the case of your mutation, but if that's not enough to convince them to give it a try, there is plenty of other information out there to build a case. If you can hand him all the evidence and all he has to do is write one letter, maybe you can change his mind.

Keep pushing!

Martha

Martha,

I am SO happy for you that you have a supportive doc and are getting Kalydeco!!! Good for him/her for going to bat for you! YAY!!! I wish my doc felt the same way. In a nutshell he said since my health has been stable I am in a good position to wait for FDA approval for my mutation. Ugh. I fundamentally disagree. I think now is the time to take it, before any more lung damage occurs!! My current FEV1 is around 65% so it's not exactly like I'm just cruising along with no lung involvement.

I want to thank you for taking the time to share your experience and for your advice. Can you tell me specifically what evidence you compiled and how you presented it? In my previous efforts I emailed the link from the power point presentation and pointed him to pages 24 and 25 (if memory serves) where my mutation is specifically covered. I stated that based on this it appears Ivacaftor has a strong likelihood of working for me. Still a no-go. Now I'm wondering if I compile this evidence physically, highlight the specific info, and then include GenH's summation of what the data is saying as well as your experience. I will also see if I can find the patent info. Were you able to find it? I haven't tried googling it or anything yet so perhaps I will come across it easily.

On another note, I am currently breastfeeding my daughter and he has stated that IF he were to prescribe Kalydeco I would have to stop breastfeeding. I have said that I would be willing to stop if it was prescribed and covered by insurance, but these are all hypotheticals. I will burn that bridge when I get there. I'm trying to decide whether or not to wait until I have wrapped up the breastfeeding before REALLY pushing him so that he can't be factoring in the breastfeeding issue when making the decision, even though I have told him I would stop if he would prescribe it.

I have a great relationship with my doc and trust and respect him. So for me this is really disappointing. I am nervous to be TOO pushy and make our relationship strained. However, this is my life we are talking about here! I feel like it's just absolutely crazy that this med is out there that has a strong likelihood of helping me but I can't get my hands on it. Ugh, I lose sleep over it at night. If only I had a couple hundred thousand dollars laying around, I'd just tell him to write the script and I'd pay for it myself!

I better run but thanks again!

Autumn

 

[lifeisgood729]

Martha,

I am SO happy for you that you have a supportive doc and are getting Kalydeco!!! Good for him/her for going to bat for you! YAY!!! I wish my doc felt the same way. In a nutshell he said since my health has been stable I am in a good position to wait for FDA approval for my mutation. Ugh. I fundamentally disagree. I think now is the time to take it, before any more lung damage occurs!! My current FEV1 is around 65% so it's not exactly like I'm just cruising along with no lung involvement.

I want to thank you for taking the time to share your experience and for your advice. Can you tell me specifically what evidence you compiled and how you presented it? In my previous efforts I emailed the link from the power point presentation and pointed him to pages 24 and 25 (if memory serves) where my mutation is specifically covered. I stated that based on this it appears Ivacaftor has a strong likelihood of working for me. Still a no-go. Now I'm wondering if I compile this evidence physically, highlight the specific info, and then include GenH's summation of what the data is saying as well as your experience. I will also see if I can find the patent info. Were you able to find it? I haven't tried googling it or anything yet so perhaps I will come across it easily.

On another note, I am currently breastfeeding my daughter and he has stated that IF he were to prescribe Kalydeco I would have to stop breastfeeding. I have said that I would be willing to stop if it was prescribed and covered by insurance, but these are all hypotheticals. I will burn that bridge when I get there. I'm trying to decide whether or not to wait until I have wrapped up the breastfeeding before REALLY pushing him so that he can't be factoring in the breastfeeding issue when making the decision, even though I have told him I would stop if he would prescribe it.

I have a great relationship with my doc and trust and respect him. So for me this is really disappointing. I am nervous to be TOO pushy and make our relationship strained. However, this is my life we are talking about here! I feel like it's just absolutely crazy that this med is out there that has a strong likelihood of helping me but I can't get my hands on it. Ugh, I lose sleep over it at night. If only I had a couple hundred thousand dollars laying around, I'd just tell him to write the script and I'd pay for it myself!

I better run but thanks again!

Autumn

Autumn,
it's a lot of information that I submitted, so it would be easier for me to email it to you. Send me a message with your email address.

Martha

 

[triples15]

Martha, PM sent! THANK YOU!

Autumn

 

[ccsalema]

Any Maine R117Hers out there...Mass General is looking for participants for their Kalydeco trial for this mutation. Here is the link for trial information. Please get in touch with Mass General CF staff (617-726-8707) if you meet the criteria. Here is the link:
http://clinicaltrials.gov/ct2/show/study/NCT01614457?term=R117H&rank=1&show_locs=Y#locn
My son is seen at MGH and is not the right mutation for this trial--they are looking for more folks to enroll so if you are R117H and in the vicinity of Boston, give a shout out to them...Go Kalydeco!

 

[triples15]

Hey everyone, it's me again.

I have finally been in contact with Connie St.Clair at Denver. The good news is, she feels as though I should come be screened for the study and has sent me the info and consent forms. The bad news is that I do not qualify on the "residual pancreatic function" so my sweat test would have to be at or under 80 at screening to get in. As I previously mentioned, when I was diagnosed it was 83. She feels I still have a "good chance" of making it in.

I guess my question is this; wouldn't my sweat chloride very likely be HIGHER now as an adult than as a 3 month old? I've read that generally sweat chloride (even in non-CFers) is higher in adults than in infants. I guess why I'm asking is that I'm a bit apprehensive to travel to Denver and have the full-day workup only to be told my sweat chloride is 100. I'm leaning toward just going because I want to get into this study so badly. However, my gut tells me it would be a wasted trip. I also had thoughts of seeing if my local clinic would be willing to sweat test me again just to see if it is way over 80. Then I'd know I could save myself the trip and the poking and prodding. The problem with this is that I'd prob have to pay for the sweat test out-of-pocket since my insurance would wonder why the heck I was having it done. If it was anywhere near 80 I would still go, just hoping it would be 80 or under at Denver.

If anyone has any thoughts about sweat chloride levels as we get older I'd appreciate it!!

Thanks everyone,

Autumn

Disclaimer: After writing this I realized if I read it as an outsider I would think "shut-up and just go to Denver for the screening, what would it hurt?". So I guess I just want to add that I have a 13 month old daughter who I've never spent more than a few hours away from and would probably be traveling to the screening with me since I would be staying overnight, thus needing to bring my husband or mom along to watch her during the testing. Also I have an extreme fear of flying so for the screening I'd probably drive the 7 hours (one way). So going to the screening will be a bit of undertaking, and it'd be so much easier if I could find out that I'm nowhere near the sweat chloride level before I went. If I got into the study I'd have to suck it up and fly, as she said for the shorter appointments they generally fly you in and out on the same day. Anyway, there's my disclaimer.

 

[welshwitch]

Autumn, that's fantastic news! Get on that plane and tell us what you find out -- this could be a chance of a lifetime!

 

[cftrsplicing]

Let us know something as soon as you can.
I'm almost in your same condition.
Screened at 3months, residual cftr mutation (2789+5g->A), sChloride at screening 87. age 31.
I think I'm slightly pancreatic sufficient since I don't get Creon and gain weight. But Dr Stclaire told me i couldn't fit in the study 'cause I'm from Europe. It'd be too expensive for the trial to give me a go and reimbursate every flight. I asked to be checked remotely but she told me they needed the same pft machine etc for reliability of datas. So.. let us know your trip results.

 

[Aboveallislove]

Autumn,
When I read (prior to your disclaimer) my thought was the opposite--oh that has to be hard decisions, that's alot to do without being pretty sure you'd be in. And then I thought just what you said, get your SC at local clinic and see if close to 80. Also, I'm pretty sure I've read that some things can affect the test. I'd research that and do whatever possible to keep it as low as possible (I think just not having salt is one for a few days before is one.) And do for trial and then if you go to Denver. The reason I suggest this is b/c if you are that close to 80, I would think the drug will help you whether or not you'd be 84 (with salt) or 79 (without), and especially if you are going to make all the arrangements to go, you'd want to make the best chance of getting in! Good luck.
-Love

 

[lifeisgood729]

Autumn, I recently repeated my sweat test before I started taking Kalydeco. I thought I remembered the number from my childhood test being in the mid 60's, so I expected it to be higher now. It came back at 54. I guess the number doesn't always rise when you get older. As for your fear of flying, my husband is the same way so I totally understand why you have to factor that into your decision. Maybe it would be best to get tested near home soon. If you're anywhere close to 80 then go for it and enter the study. It will be hard with a small child, but remember, you're doing this so you can be around for her for many years to come!

Martha

 

[cfsucks]

Let us know something as soon as you can.
I'm almost in your same condition.
Screened at 3months, residual cftr mutation (2789+5g->A), sChloride at screening 87. age 31.
I think I'm slightly pancreatic sufficient since I don't get Creon and gain weight. But Dr Stclaire told me i couldn't fit in the study 'cause I'm from Europe. It'd be too expensive for the trial to give me a go and reimbursate every flight. I asked to be checked remotely but she told me they needed the same pft machine etc for reliability of datas. So.. let us know your trip results.

honestly if you can afford the flights- or even move to the states for the study temporarily i'd do it.

 

[triples15]

Autumn, that's fantastic news! Get on that plane and tell us what you find out -- this could be a chance of a lifetime!

Thanks Claire, still thinking on it! I'll let you know for sure. If my memory serves, you were maybe going to try to get into this study? Did you find anything out?

 

[triples15]

Let us know something as soon as you can.
I'm almost in your same condition.
Screened at 3months, residual cftr mutation (2789+5g->A), sChloride at screening 87. age 31.
I think I'm slightly pancreatic sufficient since I don't get Creon and gain weight. But Dr Stclaire told me i couldn't fit in the study 'cause I'm from Europe. It'd be too expensive for the trial to give me a go and reimbursate every flight. I asked to be checked remotely but she told me they needed the same pft machine etc for reliability of datas. So.. let us know your trip results.

Cftr,

Wow, it seems we do have a lot in common- 3 months when diagnosed, sweat chloride of 83, residual function mutation, age 32. VERY similar. I also have the need for few to no enzymes. However, I have had pancreatitis multiple times and St. Clair said they are seeing very low fecal elastase numbers in CFers who have had pancreatitis. My elastase number was 25, it needed to be over 200 to fit that criteria of the study. So my number is very low for someone who seemingly is mostly pancreatic sufficient. Which leaves it up to me making it in on sweat chloride........ we'll see!

I'm sorry you can't come to be screened! I wish they could do some of the testing remotely. That would be GREAT! The study requires approximately 12 trips so it will be a lot of travel if I get in.

I will let you know what I find out for sure!!

 

[triples15]

Autumn,
When I read (prior to your disclaimer) my thought was the opposite--oh that has to be hard decisions, that's alot to do without being pretty sure you'd be in. And then I thought just what you said, get your SC at local clinic and see if close to 80. Also, I'm pretty sure I've read that some things can affect the test. I'd research that and do whatever possible to keep it as low as possible (I think just not having salt is one for a few days before is one.) And do for trial and then if you go to Denver. The reason I suggest this is b/c if you are that close to 80, I would think the drug will help you whether or not you'd be 84 (with salt) or 79 (without), and especially if you are going to make all the arrangements to go, you'd want to make the best chance of getting in! Good luck.
-Love

Love,

Thanks so much for your message. It made me feel better that you affirmed it is a tough decision, that I'm not just being a baby.

I called my clinic on Thursday to see about getting a sweat test run there and how it would work (would ins. pay? would I have to pay out-of-pocket? could they do it under the radar?). I haven't heard back from them yet, which is odd because they are usually very quick with replies. I'm really hoping there is a way to do it here. I need to know soon so I can let Denver know whether I'm coming or not. Would hate for my spot to be taken while I'm twiddling my thumbs.

Thanks for the advice RE: the sweat test. I would definitely do what I could to make it as low as possible. I'm gonna do a little research! I agree, it's not like I'm trying to change it dramatically in a way that it would effect the study. I don't think there's much difference between an 83 and an 80 in terms of how I would respond to Kalydeco.

Thanks again,

Autumn

 

[triples15]

Autumn, I recently repeated my sweat test before I started taking Kalydeco. I thought I remembered the number from my childhood test being in the mid 60's, so I expected it to be higher now. It came back at 54. I guess the number doesn't always rise when you get older. As for your fear of flying, my husband is the same way so I totally understand why you have to factor that into your decision. Maybe it would be best to get tested near home soon. If you're anywhere close to 80 then go for it and enter the study. It will be hard with a small child, but remember, you're doing this so you can be around for her for many years to come!

Martha

Thanks Martha! That is very good to know! I was just under the assumption that it almost always rose as we got older. I'm still waiting to see if I can have the sweat test done locally, but mostly leaning toward heading to Denver if they can't do one here. I agree on the baby thing. She is the biggest reason I want/need to get on Kalydeco. So I can stay healthy for a LONG time. She's definitely my motivation, but at the same time having her makes the logistics of this study a little tougher. We'll figure it out though!

I know a lot of people don't understand about the flying. To be honest, years ago I wouldn't have either. My fear has progressed over the years into a full-blown phobia. So much so that normally upon take off I am so terrified I am in tears. It's pretty bad, and I know it sounds ridiculous. No matter how hard I try to be rational and tell myself how safe it is, I'm just in a full blown state of panic. I literally just think "oh my God, I've gotta get off this thing!" when we're in mid-air and obviously that is not an option. I almost crawl out of my skin. It doesn't help that I just had the worst flights EVER last summer and guess where the problem was DENVER. Ugh. I said I'd never fly into Denver again. So of course the study would be in Denver. If I get into the study I will look into getting some Xanax or other anxiety med to see if that would help. Anyway, that's another reason it's a lot for me to consider when thinking about this study. Just makes me sick because I want in so badly but the fear of flying is very real. And to say I'm going to do it 12 times in a short period. Wow!

Thanks again!

Autumn

 

[lifeisgood729]

Autumn, definitely look into getting some xanax. My husband got a prescription from his doctor before our last flight and it seemed to help. It doesn't eliminate the phobia, but it makes it bearable to get through the flight. For him it's take off and landing that are the worst, so he's also tried sleeping pills so he is not awake for the take off. I don't know if that's a good idea for someone traveling alone, though.

 

[welshwitch]

Hi Autumn,

You have a great memory! I had ideas about trying to do more research but am a bit overwhelmed of where to start. For the record, my mutations are n1303k and

621+1G->T. I know it's kind of a rare combo for CF and if I thought I had a shot I would put some serious time into it. Did you gather all your info from this site or elsewhere? And you used it to argue your case, correct?

--Claire​

 

[cftrsplicing]

Cftr,

Wow, it seems we do have a lot in common- 3 months when diagnosed, sweat chloride of 83, residual function mutation, age 32. VERY similar. I also have the need for few to no enzymes. However, I have had pancreatitis multiple times and St. Clair said they are seeing very low fecal elastase numbers in CFers who have had pancreatitis. My elastase number was 25, it needed to be over 200 to fit that criteria of the study. So my number is very low for someone who seemingly is mostly pancreatic sufficient. Which leaves it up to me making it in on sweat chloride........ we'll see!

I'm sorry you can't come to be screened! I wish they could do some of the testing remotely. That would be GREAT! The study requires approximately 12 trips so it will be a lot of travel if I get in.

I will let you know what I find out for sure!!

I guess that they will finally be able to test remotely according to this trial results.
They are in discussion with FDA and EMA on what are the biomarkers for the activity of kalydeco on residuals.
Residuals usually have a better decline in Lung function and fewer esacerbations or related diseases.. in youth at least.

I.e. my FEV1 is in the range of 90-100, even if with bronchiectasis and much phlegm.
I'm colonized with SA and sporadically with MRSA but not still with PA.
I'm pancreas sufficient but assuming fatty meals requires some enzymes.

I don't think, as you, to be eligible for this study even if I could pay for travels to Denver.
I don't know my f-elastase data, I'll know in a week.
I was diagnosed early, even if my CF came out at 15-16 I followed a CF routine since 1 year old.
I guess my SChloride was 87 but should be about 100 now, because of my splicing mutations that allow a mild phenotype but usually translate in a high value of Sweat Chloride (a lot of papers on patients with my alleles demonstrate this).

For this reason I think that I will struggle to have access to kalydeco. I even created a site www.cftrsplicing.com with all the scientific datas I could find online.
My aim is to let people with CF TRY ivacaftor. And then decide if it works.. or not.
I think that it could even be functional to stop mutations that maintain a certain part of the protein been made.