Kalydeco and Class IV Mutations

[GenH]

Triples15- sweat chloride does generally increase slightly with age, this study http://www.ncbi.nlm.nih.gov/pubmed/18589442 found the following results in a non CF population:

The estimated median (95% RI) for sweat chloride were: 5 to 9 years, 13 mmol/L (1-39 mmol/L); 10 to 14 years, 18mmol/L (3-47 mmol/L); 15 to 19 years, 20 mmol/L (3-51mmol/L); and 20+ years 23 mmol/L (5-56mmol/L).

I personally was 110 at age 3 when I was diagnosed and now 102 at age 27. At age 3 I did not sweat much and only just got to the 80mg weight (any lower and often they will retest as the results may not be accurate). I think this is why it was higher. At age 3 I also had a test before this with a weight of 40mg and sweat chloride of 130, but this was repeated as they said it was inaccurate due to the low weight.

I guess I'm just saying there are other factors that can influence the test (like aboveallislove said with the salt intake), and I know of a few people who have tested lower later in life (but this could be to do with the testing, eg the weight as I mentioned above and the testing is probably more accurate now than 20 years ago as well).

I hope you can get Kalydeco soon

 

[rmotion]

It's true! These docs don't have CF - no matter how empathetic they are, they will NEVER fully know what it's like to have this disease. So they don't have the same sense of urgency that we do. ESPECIALLY if you are near Tx. Does their life change dramatically when you get to end stage and need a tx? NO. Do they have to be on immunosupressants for the rest of their lives? Avoid big crowds? Worry about their future? NO NO NO! How could you NOT let a patient try this drug? The drawbacks/side effects are so minimal it's INEXCUSABLE not to let a patient with any mutation try it. If you aren't vocal, you can let these docs slowly take away your health. And your life. OK I'll stop now.

Its not the doc its the insurance companies. If you dont have G155 they wont approve it, well some people with df508 got it through. If you had the cash you could get a script from any doc. But what makes this so sad is that we all should be able to try it to see if it works. My thinking is Vertex does not want to say do it it might work and it gets them in trouble for their bigger market the df508 - jsut think 70k people worldwide x $300K big bucks for them.
vx770 showed it worked 5% or so in df508 - that is a good number especially if it helps other parts of our problems.

 

[triples15]

Hey everyone, me AGAIN!

I'm still sitting here on the fence about the Denver study. I wanted to run a couple things by the experts on here.

So, first question I have is that if someone participates in a phase 2 trial does that automatically exclude them from participating in a phase 3? Just thinking a phase 3 is more likely to have an expanded access program at the end where I could continue on Kalydeco. I asked the research coordinator if there was an expanded access after this study and she said she had asked Vertex about this and they had not responded. She said it was possible there would be, but at this point no one knows.

As far as the actual study it looks like it is structured as follows:

Cycle 1- 29 days, receiving either Ivacaftor or placebo
Wash out period no less than 4 weeks where you're receiving neither placebo nor ivacaftor
Cycle 2- 29 days, receiving either ivacaftor or placebo
Another 4 week wash out period
Open label, 8 weeks of ivacaftor

The 4 week washout periods have me a little nervous because if Kalydeco helps me as much as I'm hoping it will, it won't be fun to have to have the rebound period where I feel like crap again. Also I'm nervous about what happens if it is really really helping me during that 8 week open label and then all of a sudden I just have to go off of it cold turkey. Ugh, that would be awful, but is a very likely possibility. That's why I was hoping so badly that there would be an expanded access program.

Anway, these are my new thoughts, in addition to my previously mentioned ones!

Feel free to weigh in!

Thanks again,

Autumn

 

[cfsucks]

Hey everyone, me AGAIN!

I'm still sitting here on the fence about the Denver study. I wanted to run a couple things by the experts on here.

So, first question I have is that if someone participates in a phase 2 trial does that automatically exclude them from participating in a phase 3? Just thinking a phase 3 is more likely to have an expanded access program at the end where I could continue on Kalydeco. I asked the research coordinator if there was an expanded access after this study and she said she had asked Vertex about this and they had not responded. She said it was possible there would be, but at this point no one knows.

As far as the actual study it looks like it is structured as follows:

Cycle 1- 29 days, receiving either Ivacaftor or placebo
Wash out period no less than 4 weeks where you're receiving neither placebo nor ivacaftor
Cycle 2- 29 days, receiving either ivacaftor or placebo
Another 4 week wash out period
Open label, 8 weeks of ivacaftor

The 4 week washout periods have me a little nervous because if Kalydeco helps me as much as I'm hoping it will, it won't be fun to have to have the rebound period where I feel like crap again. Also I'm nervous about what happens if it is really really helping me during that 8 week open label and then all of a sudden I just have to go off of it cold turkey. Ugh, that would be awful, but is a very likely possibility. That's why I was hoping so badly that there would be an expanded access program.

Anway, these are my new thoughts, in addition to my previously mentioned ones!

Feel free to weigh in!

Thanks again,

Autumn

hey are you in the facebook group...

http://www.facebook.com/groups/153375788050316/

you might get more response there

 

[rmotion]

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

If you can get into the study I would go and stay the 2 months in an extended stay apartment or what not. maybe there is a family exchange like penpals you could stay with.

 

[triples15]

Hey everyone, thanks for the responses! There were a couple that I missed until now so I apologize for not responding.

I have an update in case anyone is still following this thread....

I did not make it to Denver to be screened back in February, as I ended up with a nasty exacerbation that landed me on IVs for 4 weeks and still was not back up to baseline. By the time I was back to "normal", the enrollment was complete. UGH.

But now I have gotten a second chance! Connie St. Clair notified me a few weeks ago that they are enrolling a few more participants and asked if I was still interested! So I am going to Denver next week!! Crazy. Screening will be on the 3rd and 4th (Sept), and then I'm not sure how quickly I'll know if I'm in or not. I'm assuming it will be quick.

We are driving for the screening, and then IF i get into the study I will tackle the flying issue.

I will for sure keep everyone posted.

Thanks, and take care everyone!

Autumn 32 w/CF

Oh, and PS. I am going to try to avoid salt for the most part until I go next week. I've got my fingers crossed that sweat test comes in at or under 80. If anyone else has any brilliant ideas, let me know!

 

[welshwitch]

Great news! Keep us posted on your progress!

 

[triples15]

Great news! Keep us posted on your progress!

Thanks!! I will you posted for sure!!

 

[LittleLab4CF]

triples15
Just curious, are you looking at the trials going on a NJH, (National Jewish Health) in Denver?

LL

 

[triples15]

Yep LL, it's the Kalydeco trial for residual function mutations at Denver National Jewish.

Heading out to be screened for it in a few days. Fingers crossed!

 

[jricci]

Martha- I just sent you a PM. I was wondering if you could help me regarding the information you provided insurance company while seeking approval for Kalydeco for residual function mutations. Thank you!

 

[triples15]

Martha- I just sent you a PM. I was wondering if you could help me regarding the information you provided insurance company while seeking approval for Kalydeco for residual function mutations. Thank you!

Hey J,

Let me know if you don't hear from Martha. I'm not sure how often she's around here, but I did just see her post yesterday, so hopefully she gets your message. She's a better source, but I have the information she sent me to try to help me get it off label. It didn't work for me , but you should absolutely give it a try! I should clarify that my doctor wouldn't write me the script, so I never even got to the battling with the insurance company stage. Boo.

Anyway, let me know if you want/need the info she gave me.

Take care and good luck!!

Autumn 33 w/cf

 

[jricci]

Hi Autumn,
Martha replied already, but thank you so much for your offer. I'll let you know how it goes. Fingers crossed.
Take care,
Jeannine

 

[triples15]

Awesome!! Good luck again, I so hope you are able to get it. Do keep us posted please!

Autumn

 

[stephen]

Kalydeco DEFINITELY can work for some Class 4 mutations - and work well.

I really can't understand why some doctors are reluctant to even try prescribing it! If the insurance provider turns it down, that's another story - although some doctors have been successful in getting insurance providers to rescind their initial denials. At least try.

 

[Aboveallislove]

I totally agree with Stephen! Why a doctor would be unwilling to script this off label is beyond me. It has an extremely safe profile. Insurance coverage is a separate question. If you search your insurance plan (which should be on line), you'll see a discussion of off label coverage. In general, insurance covers off label if there is medical evidence (usually peer-reviewed type evidence), that it works. Hopefully when more data I published on phase 2 Denver and possibly case studies, there is more ammo for forcing insurers to cover.

 

[triples15]

Amen to Stephen and Love. I have NO idea why my doctor wasn't even willing to try.... his only answer was basically that they weren't prescribing it off-label because they had tried for a couple other patients and insurance was denying... Also that Vertex wouldn't provide any copay assistance for off-label use.

I presented him with the info I got in another thread and from the info Martha sent me. This info included that my residual function mutation (S945L) is included in the Kalydeco patent. Also info from Vertex that showed that in the early trials, Kalydeco alone potentiated even more function in my mutation than in G5551d. If memory serves, up to 70% function! Blah!! I can't put into words how badly it bothers me that I can't get it, and no one will even try.

Anyway, that's my story.. Maybe I need to go see Stephen's doctor?

Autumn 33 w/cf

 

[jricci]

Well I have an update! It’s a long one. My doctor attended the NACFC and spoke to other doctors about their experiences with off label Kalydeco use for residual function mutations. After hearing many success stories, he decided to prescribe it for me. He was cautiously optimistic that it would help me since I’m pancreatic sufficient (have residual function). My mutations are DDF508 and r334w. (r334w is a class IV conductance mutation. It is one of the few conductance mutations that did not show a significant response to Kalydeco in in-vivo studies.) We were expecting pushback from my insurance company and we were armed with a lot of information to appeal if it was denied. But my insurance company covered it immediately, no questions asked. I started Kalydeco 5 days ago. My lung function was at 31% (this was after an unsuccessful round of IV antibiotics. I would say I consider my baseline lung function to be in the upper 30’s/low 40’s). I began noticing a difference within a matter of days! The biggest change I noticed was decreased inflammation. I have had a lot of issues with wheezing in the last 3 years. I could feel my lungs opening up by the 4[SUP]th[/SUP] dose. I took a deep breath in the cool outside air and could feel the air reaching parts of my lungs that I haven’t felt in a very long time. Another big change I’ve noticed is that my mucus is thinner, similar to what it is after a hypertonic saline treatment, except it was this consistency the whole day! I did a repeat PFT today and my lung function was up to 41%. 31% to 41% in 5 days! My doctor said he couldn’t remember the last time my lungs sounded so good. Unbelievable! I asked my doctor if Vertex was keeping a database of mutations that have responded/not responded to the off-label use of Kalydeco. He said that the CFF collects data for the registry and this information would be included but it is only released annually. I plan on calling Vertex and asking them if there is any way for them to keep track of off label use. It only makes sense that this information should be officially collected and shared with patients and doctors alike. But in the meantime, I’ll share my story via this forum in the hopes that it will help others with residual function mutations. Here’s to new beginnings…

 

[Aboveallislove]

How absolutely wonderful! Can you push your doctor to write up a case study for publication? It could help other doctors decide to prescribe or help other patients fight insurance companies. Also if you aren't aware, vertex will be doing a combo trial next year and the 661/kalydeco trial should help you even more...and in the meantime, you should be ready to push to try the 809/kalydeco trial in marching when approved by FDA since the combos showed further improvement for those with 551 mutatin who had been only on kalydeco...I am so happy for you!

 

[triples15]

Well I have an update! It’s a long one. My doctor attended the NACFC and spoke to other doctors about their experiences with off label Kalydeco use for residual function mutations. After hearing many success stories, he decided to prescribe it for me. He was cautiously optimistic that it would help me since I’m pancreatic sufficient (have residual function). My mutations are DDF508 and r334w. (r334w is a class IV conductance mutation. It is one of the few conductance mutations that did not show a significant response to Kalydeco in in-vivo studies.) We were expecting pushback from my insurance company and we were armed with a lot of information to appeal if it was denied. But my insurance company covered it immediately, no questions asked. I started Kalydeco 5 days ago. My lung function was at 31% (this was after an unsuccessful round of IV antibiotics. I would say I consider my baseline lung function to be in the upper 30’s/low 40’s). I began noticing a difference within a matter of days! The biggest change I noticed was decreased inflammation. I have had a lot of issues with wheezing in the last 3 years. I could feel my lungs opening up by the 4[SUP]th[/SUP] dose. I took a deep breath in the cool outside air and could feel the air reaching parts of my lungs that I haven’t felt in a very long time. Another big change I’ve noticed is that my mucus is thinner, similar to what it is after a hypertonic saline treatment, except it was this consistency the whole day! I did a repeat PFT today and my lung function was up to 41%. 31% to 41% in 5 days! My doctor said he couldn’t remember the last time my lungs sounded so good. Unbelievable! I asked my doctor if Vertex was keeping a database of mutations that have responded/not responded to the off-label use of Kalydeco. He said that the CFF collects data for the registry and this information would be included but it is only released annually. I plan on calling Vertex and asking them if there is any way for them to keep track of off label use. It only makes sense that this information should be officially collected and shared with patients and doctors alike. But in the meantime, I’ll share my story via this forum in the hopes that it will help others with residual function mutations. Here’s to new beginnings…

Totally AMAZEBALLS!! So happy for you! Thank goodness for the NACFC! Whoo hoo! I hope you just keep feeling better and better.

I recently moved and *sort of* broached the subject with my new doc in September. I didn't want to be too pushy since it was his first time meeting me. At my December visit I may come armed with all of my evidence that I presented my old doctor with and lobby hard. I don't understand what just trying will hurt. As you saw, the insurance covered it! My mutation is one that showed the most improvement in the in-vivo studies, so it's so frustrating to just keep waiting.... (have I mentioned that before )

Anyway, congrats to you! Thanks for the update and please keep us posted.

Autumn 34 w/CF