I just saw my healthcare team and was told that I qualify for an experimental treatment protocol, apparently Ivacaftor now covers 23 mutations and I have one of those mutations. I am still waiting to see if I get accepted into the study, but I was wondering if anyone is/has taken Ivacaftor and what you think of the medication. I have already had the discussion with my doctor but I really just want to hear from someone who has taken the medication
taking Ivacaftor?
- Thread starter LunaFaith
- Start date
I've been taking it since 2014 - I'm sure there are a number of other people on here too. I heard they expanded the label for Kalydeco recently so I assume you have one of those mutations? I have a very rare residual function mutation and am unfortunately still off label (my mutation is too rare to appear in the CFTR2 database and hasn't been studied!). I've had a great experience on it - no side effects, my PFTs increased, sweat chloride decreased, gained weight, etc. It hasn't been a dramatic change but has definitely stabilized things. My maximum FEV1 used to top out around 60% and it's increased to 65% - and previously, when I had exacerbations my FEV1 used to drop into the 40s and 30s. Now, even when I'm feeling quite sick, I seem to always stay above 50% and recover quickly to baseline once I get on the right antibiotics. I always had very mild GI issues but they're now practically nonexistent (I require almost no enzymes). Hope this is helpful!
stephen
Super Moderator
My advice is to try getting Kalydeco if you possibly can!
I’ve been very fortunate in that my CF center prescribed Kalydeco for me off-label over three years ago. It’s been a real life changer. After 60 years, my cough and thick mucus production disappeared! It took less than a day to start feel its positive effects, and there haven’t any negative reactions that I’m aware of.
As I’ve said before, it’s a shame that all CF centers were not as proactive as mine, and resisted to even try getting Kalydeco off-label for all their patients with Residual Function mutations. I don’t know if they were afraid to put in the extra effort that might have been required, or were just not familiar with the positive data that existed. My center was eventually successful in getting Kalydeco off label for six of the eight patients for whom they tried.
My D1152H mutation was among those just approved by the FDA. While I never had any real problems getting it off-label, there were two instances when renewals were initially denied. Both times my CF center promptly submitted appeals, and the denials were reversed within two days.
Again, I say go for it. Kalydeco doesn’t seem to have the adverse side effects reported for Orkambi.
Good luck!
I’ve been very fortunate in that my CF center prescribed Kalydeco for me off-label over three years ago. It’s been a real life changer. After 60 years, my cough and thick mucus production disappeared! It took less than a day to start feel its positive effects, and there haven’t any negative reactions that I’m aware of.
As I’ve said before, it’s a shame that all CF centers were not as proactive as mine, and resisted to even try getting Kalydeco off-label for all their patients with Residual Function mutations. I don’t know if they were afraid to put in the extra effort that might have been required, or were just not familiar with the positive data that existed. My center was eventually successful in getting Kalydeco off label for six of the eight patients for whom they tried.
My D1152H mutation was among those just approved by the FDA. While I never had any real problems getting it off-label, there were two instances when renewals were initially denied. Both times my CF center promptly submitted appeals, and the denials were reversed within two days.
Again, I say go for it. Kalydeco doesn’t seem to have the adverse side effects reported for Orkambi.
Good luck!
I see - check out this link from Vertex (the manufacturer) that lists the 23 additional mutations that it was recently approved for: https://www.kalydeco.com/additional-mutations/
I'd suggest discussing further with your doctor if your mutation is already approved!
I'd suggest discussing further with your doctor if your mutation is already approved!
Hi everyone. My daughter has D110H and will soon be starting kalydeco. She is 4 and has never been on antibiotics or been hospitalized. She only has cultured staph. Her doctor said now is the time to start this medicine. How will I know it's working?? (She isn't very symptomatic)
we discussed it at length before I was ever given any paperwork to sign, I am just waiting to see if I get approved, my lung function isn't getting any better and only really gets worse when I'm sick, but I have been stuck in the 30's for the last 9 years, I am hoping that I get approved, anything to help my lung function
Jeannie85: Talk with her doctors, but I'd suggest doing a sweat test before and after starting it. It's a quantitative measure of improvement that might be useful if you have any issue with insurance companies in the future, and is generally good to know! That's great she is so healthy. Ideally, Kalydeco will keep things that way and prevent any damage to her lungs in the future. I have read the blog of a woman who also had a child start on Kalydeco at age 4 (http://luckycfmom.blogspot.com/) - as I recall, he was also not very symptomatic but they noticed a big improvement in his sinuses. I personally had an improvement in my GI issues (which were pretty minor to start with). Good luck - very exciting!
SarahProcter
New member
Jeannie85: definitely do sweat tests before and after starting ivacaftor (4-8 weeks after). You should also do blood work to get baseline values for liver function and pancreatic function (amylase, lipase). My daughter started at 7 in a similar situation - very healthy so no dramatic difference in her day to day life. But her sweat test came down to a NORMAL value (I still can't say that without yelling NORMAL), and her pancreatic values which had been a little elevated came back to normal as well. The liver function tests are to make sure that ivacaftor doesn't fuss her liver.
Having my daughter's sweat test go from clearly diagnostic for CF down to normal lifted an enormous weight off me that I'd been carrying for seven years.
Having my daughter's sweat test go from clearly diagnostic for CF down to normal lifted an enormous weight off me that I'd been carrying for seven years.
Thanks for all the responses! I was informed about the liver levels needing to be checked q3months. Also have an eye exam scheduled to check for cateracts. But the doctor never mentioned getting a sweat test. Should I ask and push for it? The pancreatic function wasn't mentioned but she has always been sufficient. Did your daughter feel any different Sarah?
jenjoeyswife
New member
My husband (53 years old) has been on Kalydeco since its release in Feb. 2012 (He's G551D). He has not been given a sweat test at all, but wish he would have. However, this year is the first summer he has really needed antiperspirant in his life, so clearly he's really sweating and I'm thinking he's at the normal level! He's always just salted up, which made him the dog/cat magnet.
He had an initial spike in his PFT's (up to like 83%), but it has gone back down as low as 63%, but he's back up (April) to 67%
Weight gain is easy now and he's had no adverse side effects of K. Good Luck!
He had an initial spike in his PFT's (up to like 83%), but it has gone back down as low as 63%, but he's back up (April) to 67%
Weight gain is easy now and he's had no adverse side effects of K. Good Luck!
SarahProcter
New member
Totally get a sweat test. It proves it's working. My daughter is so healthy she didn't feel different.
Hi! I just saw in another post here that you have one of the splice mutations that Vertex want to discuss label expansion for, the 2789+5G->A ? Do you know the name of the study you would participate in? I’m curious because I also have a splice mutation (pancreatic sufficient) but my mutation is so rare it is never included in any trials but I’m hoping that if more and more residual function splice site mutations become included in the label, then eventually all residuals - even splice mutations - will get *a chance to try Kalydeco. I agree with everyone else here that you should absolutely seize the opportunity to try Kalydeco!!
on my consent paperwork has this on it, hopefully some part of this is helpful, I also have yet to be contacted so I may not have qualified, they ran some blood work to see if what they need to be ok, is ok, I have no better way to explain that one, lol I also don't know what all they were looking for though I do know one thing was liver function
University of North Carolina at Chapel Hill Consent to Participate in an Experimental Treatment
IRB Study # 17-0197
Title of Protocol Ivacaftor Therapy Expanded Access Program for Patients with Selected Residual Function Mutations on a CFTR allele
University of North Carolina at Chapel Hill Consent to Participate in an Experimental Treatment
IRB Study # 17-0197
Title of Protocol Ivacaftor Therapy Expanded Access Program for Patients with Selected Residual Function Mutations on a CFTR allele
Here's some more information regarding Expanded Access Program offered by Vertex that I think you are referring to:
Program designed for individuals 2 years or older with specific residual function genotypes and severe lung disease meeting the following criteria:
• One of 23 residual function mutations: 2789+5G- > A, 3849+10kbC- > T, 3272-26A- > G, 711+3A- > G, E56K, P67L, R74W, D110E, D110H, R117C, L206W, R347H, R352Q, A455E, D579G, E831X, S945L, S977F, F1052V, R1070W, F1074L, D1152H, and D1270N.
• FEV1 of less than 40% predicted OR decline of 20% predicted in a 6 month period and sustained for 1 month OR being evaluated for a lung transplant
This program is offered by Vertex and doesn’t go through your insurance. It’s not a clinical trial so info. can’t be found on clinicaltrials.gov. It requires that your treating physician file an IRB submission and get approval.
Physicians must submit an application to Vertex on behalf of one of their patients that meet specific criteria.
missme-
Although your mutation isn't included in this program, there is the possibility (although remote) that if you have severe disease you may qualify for consideration for expanded access. It's not a specific established "program" as described above. But the steps to apply for access are similar.
Here’s some general guidance offered by FDA on expanded access programs:
http://www.fda.gov/NewsEvents/Public...se/default.htm
As far as I know, expanded access is not limited to the US patients.
Here's an article I recently wrote for the CF Roundtable discussing Expanded Access:
http://www.cfroundtable.com/spring-2017-newsletter/#jump1
(Sadly, despite it being required by law, Vertex still does not have the required expanded access information on clinicaltrials.gov)
Here's a recent published case report of someone from Italy with severe disease who carries a splice mutation that has had great success with Kalydeco. I'm not sure how she obtained it, I'm guessing it was through the expanded access program that was described above.
Poster Sessions
42 Effects of ivacaftor in an adult patient with cystic fibrosis who carries the 3272-26A → G mutation, resulting in residual functioning protein, and has severe lung disease
http://www.cysticfibrosisjournal.com/article/S1569-1993(17)30407-1/pdf
Good Luck to both of you.
Program designed for individuals 2 years or older with specific residual function genotypes and severe lung disease meeting the following criteria:
• One of 23 residual function mutations: 2789+5G- > A, 3849+10kbC- > T, 3272-26A- > G, 711+3A- > G, E56K, P67L, R74W, D110E, D110H, R117C, L206W, R347H, R352Q, A455E, D579G, E831X, S945L, S977F, F1052V, R1070W, F1074L, D1152H, and D1270N.
• FEV1 of less than 40% predicted OR decline of 20% predicted in a 6 month period and sustained for 1 month OR being evaluated for a lung transplant
This program is offered by Vertex and doesn’t go through your insurance. It’s not a clinical trial so info. can’t be found on clinicaltrials.gov. It requires that your treating physician file an IRB submission and get approval.
Physicians must submit an application to Vertex on behalf of one of their patients that meet specific criteria.
missme-
Although your mutation isn't included in this program, there is the possibility (although remote) that if you have severe disease you may qualify for consideration for expanded access. It's not a specific established "program" as described above. But the steps to apply for access are similar.
Here’s some general guidance offered by FDA on expanded access programs:
http://www.fda.gov/NewsEvents/Public...se/default.htm
As far as I know, expanded access is not limited to the US patients.
Here's an article I recently wrote for the CF Roundtable discussing Expanded Access:
http://www.cfroundtable.com/spring-2017-newsletter/#jump1
(Sadly, despite it being required by law, Vertex still does not have the required expanded access information on clinicaltrials.gov)
Here's a recent published case report of someone from Italy with severe disease who carries a splice mutation that has had great success with Kalydeco. I'm not sure how she obtained it, I'm guessing it was through the expanded access program that was described above.
Poster Sessions
42 Effects of ivacaftor in an adult patient with cystic fibrosis who carries the 3272-26A → G mutation, resulting in residual functioning protein, and has severe lung disease
http://www.cysticfibrosisjournal.com/article/S1569-1993(17)30407-1/pdf
Good Luck to both of you.
Thanks Jeannine for your efforts to inform about the EAP! I don’t know if the Vertex’ EAP’s are valid in Europe but knowledge about these modulator drugs is really lacking here… So these are only for investigational drugs? And for drugs that have been approved but not yet for some mutations or age groups? What about when a country hasn’t yet agreed on a price for Orkambi? Would people with less than 40% FEV1 be able to benefit from the EAP/compassionate use while waiting for an agreement? *
This particular EAP on residuals must have changed a bit since most of the mutations listed above have been approved by the FDA recently. The 2789+5G->A that Lunafaith has is among the 5 splicing mutations with residual function that Vertex is still discussing with the FDA, so they would clearly be included in a EAP. ( These are the 5 splicing mutations I referred to: 3849+10kbC->T, 2789+5G->A, 3272-26A->G, 711+3A->G, E831X). I am just wondering if they have included even more splice mutations than those 5? I still don’t know why they have been so slow at including splicing mutations with residual function (class V)? Does someone know why? I also read somewhere that in vitro testing on class V splicing mutations with modulators (that can only be Kalydeco) is less reliable than in vitro testing on other mutations. Does anyone know anything about this? If so, then using organoids to achieve personalized medicine for rare mutations is going to be miss leading if the in vitro shows no effect whereas the in vivo effect could have been great. I wonder if this is the reason why splicing mutations are the last residuals that are investigated for the use of Kalydeco and that only lab tests weren’t enough for the FDA to get their approval? In that case they should offer N-of-1-trials for every single individual with a class V mutation!
LunaFiath: fingers crossed you will be accepted for this EAP!
This particular EAP on residuals must have changed a bit since most of the mutations listed above have been approved by the FDA recently. The 2789+5G->A that Lunafaith has is among the 5 splicing mutations with residual function that Vertex is still discussing with the FDA, so they would clearly be included in a EAP. ( These are the 5 splicing mutations I referred to: 3849+10kbC->T, 2789+5G->A, 3272-26A->G, 711+3A->G, E831X). I am just wondering if they have included even more splice mutations than those 5? I still don’t know why they have been so slow at including splicing mutations with residual function (class V)? Does someone know why? I also read somewhere that in vitro testing on class V splicing mutations with modulators (that can only be Kalydeco) is less reliable than in vitro testing on other mutations. Does anyone know anything about this? If so, then using organoids to achieve personalized medicine for rare mutations is going to be miss leading if the in vitro shows no effect whereas the in vivo effect could have been great. I wonder if this is the reason why splicing mutations are the last residuals that are investigated for the use of Kalydeco and that only lab tests weren’t enough for the FDA to get their approval? In that case they should offer N-of-1-trials for every single individual with a class V mutation!
LunaFiath: fingers crossed you will be accepted for this EAP!
I thought I'd tag everyone in this tread to make sure they are aware of lastest Vertex press release:
http://forums.cysticfibrosis.com/sh...o-for-5-residual-function-mutations?p=1083508
LunaFaith- it looks like you'll be trying Kalydeco soon! Please give us updates on your response.
http://forums.cysticfibrosis.com/sh...o-for-5-residual-function-mutations?p=1083508
LunaFaith- it looks like you'll be trying Kalydeco soon! Please give us updates on your response.
My daughter just had her eye exam today and it went well! Now we just wait for the rest to process. I'm getting nervous about her starting Kalydeco. I have high expectations for this to be the "miracle" that other people have experienced. Nervously anticipating the unknown!!
I hope she does well with it. I remember how exciting that first dose was. I was so hopeful that it would work, but yet so worried that it wouldn’t-- lots of mixed emotions. I know you had concerns because you weren’t sure how to know it was working because she doesn’t have symptoms. I’m not sure what you decided to do in regard to getting a post-Kalydeco sweat test done to assess response; but I wanted to mention that you can have a clinical response to Kalydeco without much change in sweat chloride levels. My sweat chloride decreased some, but it wasn’t dramatic. But my symptom improvement was dramatic. I’m not saying it’s a bad idea to get a sweat test post-Kalydeco to compare the results. If there is a decrease, that’s an indicator that it may be working. But just keep in mind if there isn’t much change, that doesn’t necessarily mean that it’s not working. It was mentioned in another thread how one of these residual function mutations, A455E, actually showed a very significant increase in sweat chloride (+27) in a few people after starting Kalydeco, which was shocking and concerning. There's no data to tell us what happens clinically when there's a significant increase in sweat chloride, but it would seem that it may worsen symptoms. I really hope Vertex and/or the CFF are carefully tracking post-marketing data since some of these mutations weren’t represented in the study and they based results on preclinical in-vitro laboratory data.
I was reading that the Lung Clearance Index is a test that's being used on younger children to assess early lung damage that isn’t yet measurable on PFTs. It’s a very sensitive test that detects changes in small airways (site of early CF lung damage).
So I’m wondering if it would make sense to get this prior to starting Kalydeco to have something to compare down the road. I don’t know much about this test at all. I’m not sure what’s involved, how invasive it is, or how expensive it is. But I thought I’d mention it so that you can discuss it with your doctor.
Here’s an case report abstract that also demonstrates that no change in sweat chloride can still equate to a very positive clinical response:
http://www.cysticfibrosisjournal.com...17)30407-1/pdf
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