residual function & Kalydeco news

ymikhale

New member
Hi all,
Does anyone has any news on the pilot study of Kalydeco and residual function mutations? On clinicaltrials.gov website it says completed and has results, but i have trouble deciphering the actual results. Maybe anyone had beteter luck?

thanks
 

Aboveallislove

Super Moderator

ymikhale

New member
Oh, thanks, I guess i missed the results of this. so basically they ar not going to do anything specific for residual function anymore from what i gather. My dd has one copy of delta 508 but she is too young. thanks for answering
 

Aboveallislove

Super Moderator
They aren't doing anything for residual function for kalydeco alone but 661 and kalydeco together will be the on label for residual function. If she's two you might try for kalydeco alone off label if her other is residual function...otherwise you'll have to wait for the 661 study approval likely about two years.
 

concerneddad

New member
Interesting information. My children have one residual function mutation and I too have been waiting the outcome of this study. I was not aware that the residual function study was "suspended" and wrapped in with the larger study involving 661. The press release issued following the proof of concept study specifically stated "Vertex plans to initiate a Phase 3 study of ivacaftor in people with residual function mutations, pending discussions with regulatory authorities regarding the design of the study." That being said, where is it stated that there won't be a separate phase III study? Is it simply because there has been no enrollment yet?

Thanks!
 

jricci

Super Moderator


This is the Phase 3 study they were referring to in the press release.
https://clinicaltrials.gov/ct2/show/NCT02392234 They just added the combo drug to one of the arms. I think people are getting confused because there are 3 arms of the trial: placebo, monotherapy with Ivacaftor (Kalydeco), VX-661/ivacaftor combination. They’re trying to determine if combo drug has even more of a benefit than Ivacaftor (Kalydeco) alone for residual function.
Also note that as of July 8th, clinicaltrials.gov site has been updated and they added more study sites that are actively recruiting. If you have a residual function mutation (pancreatic sufficient OR sweat chloride between 60-80) that is not listed in this study please post. I'm wondering what other mutations (besides mine) are "missing". Thanks

 

jricci

Super Moderator
Just realized that clinicaltrials.gov site still doesn't include which mutations. If anyone missed previous thread, you must have one df508 mutation and one of the following mutations to participate in the study:

2789+5G?A, D110E, R352Q, A1067T, 3849+10kbC?T, D110H, A455E, R1070Q,
3272-26A?G, R117C, D579G, R1070W, 711+3A?G, E193K, S945L, F1074L, E56K,
L206W, S977F, D1152H, P67L, P205S, F1052V, D1270N, R74W, R347H, K1060T

https://tools.cff.org/Display/dsp_C...S=&BCepacia=&PLT=0&Therapy=&Char=&Keyword=661

If you have a residual function mutation (pancreatic sufficient OR sweat chloride between 60-80) that is not listed in this study please post. I'm wondering what other mutations (besides mine) are "missing". Thanks
 

JDsmom

New member
Just realized that clinicaltrials.gov site still doesn't include which mutations. If anyone missed previous thread, the study is inclusive of the following mutations:

2789+5G?A, D110E, R352Q, A1067T, 3849+10kbC?T, D110H, A455E, R1070Q,
3272-26A?G, R117C, D579G, R1070W, 711+3A?G, E193K, S945L, F1074L, E56K,
L206W, S977F, D1152H, P67L, P205S, F1052V, D1270N, R74W, R347H, K1060T

https://tools.cff.org/Display/dsp_C...S=&BCepacia=&PLT=0&Therapy=&Char=&Keyword=661

If you have a residual function mutation (pancreatic sufficient OR sweat chloride between 60-80) that is not listed in this study please post. I'm wondering what other mutations (besides mine) are "missing". Thanks

If they included specific mutations they would have to mention it, right? I would suppose their inclusion parameters are clearly stated and they include every mutation accordingly. My son has R347P which is was not mentioned to respond in the in vitro studies. In real life, my son (11 years) is clearly pancreas sufficient.
 

Aboveallislove

Super Moderator
If he'll be 12 in time, there is another hetero arm that he could try to get in. Or, if he is PS, then discussing off label with his doctor would make sense too.
 

JDsmom

New member
Oh, which other hetero arm do you mean?
I would even consider to try to get him off-label on 809/orkambi as soon as he turns 12 next April....
 

jricci

Super Moderator
There is another study that is not currently enrolling, but should be soon. Your son's mutation is included (missense mutation). But you have to be 12 or older to participate.
Here's the thread that discusses study:http://forum.cysticfibrosis.com/thr...FTR-Mutation-not-likely-to-respond-to-therapy
If he's pancreatic sufficient, there's a very good chance that he will have a good response (even to Kalydeco alone). You may want to try and get off-label. You can always start the process and see what happens. Do you think your doctor would be willing to write a prescription? How is your son's pulmonary status?
 

JDsmom

New member
There is another study that is not currently enrolling, but should be soon. Your son's mutation is included (missense mutation). But you have to be 12 or older to participate.
Here's the thread that discusses study:http://forum.cysticfibrosis.com/thr...FTR-Mutation-not-likely-to-respond-to-therapy
If he's pancreatic sufficient, there's a very good chance that he will have a good response (even to Kalydeco alone). You may want to try and get off-label. You can always start the process and see what happens. Do you think your doctor would be willing to write a prescription? How is your son's pulmonary status?
Thanks! I will follow this study. But not sure - as we are in Switzerland we have limited access to the studies and we just there was just the chance to participate in the current 661 combo study for DD508 and residual function. But as my son being too young no way of getting into. Status is that he had a major decline in function during the last 2 years and sits at 92% with obviously first time chronic PA infection. Because of the poor prediction of his benefit to Kalydeco we did not even try to get it off-label so far. As far as I know only very few kids & adults in Switzerland are on Kalydeco alone and they are not off-label.
 

ymikhale

New member
I am confused because as JDsmom said, the study is aimed at heterozygous DF508 people, my understanding is that it does not target specifically residual function.[h=1][/h]
 

Aboveallislove

Super Moderator
One of the studies is for those with df508 on one allele and the other mutation a residual function one. They don't have for those with one residual function and one other mutation which isn't believed to benefit. It would seem if the residual function alone benefits from Kalydeco as the studies show (and df508 doesn't), then those with a residual function mutation and another non df508 would benefit from Kalydeco and or 661 or 661 and combo. But no studies for that yet...but once residual function with df508 is approved off label might be an option.
 

MissMe

New member
Hi! I'm new to this site and forum. My previous post got lost while I was writing it... so I gues I'll have to try to write less and faster. I have one of the mutations listed in the Denver study; the 4005+2T->c but it was NOT among the 23 residual ones in Vertex's application to the FDA early this year. I wonder why some were left out...
I am pancreatic sufficient and really hope I will get to try Kalydeco one day in a not to distant future. I live in Sweden, so off label isn't a possibility here.
I also wonder weither the phase 3 you are refering to here with heterozygote deltas will be proof enough for the FDA or EMA to approve Kalydeco for residual/splicing mutations that dont have a delta on the other allele? My other mutations is a nonsense mutation but Ataluren doesn't even remotely look as promising as the results from.the denver study.
 
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jricci

Super Moderator
Hi! I'm new to this site and forum. My previous post got lost while I was writing it... so I gues I'll have to try to write less and faster. I have one of the mutations listed in the Denver study; the 4005+2T->c but it was NOT among the 23 residual ones in Vertex's application to the FDA early this year. I wonder why some were left out...
I am pancreatic sufficient and really hope I will get to try Kalydeco one day in a not to distant future. I live in Sweden, so off label isn't a possibility here.
I also wonder weither the phase 3 you are refering to here with heterozygote deltas will be proof enough for the FDA or EMA to approve Kalydeco for residual/splicing mutations that dont have a delta on the other allele? My other mutations is a nonsense mutation but Ataluren doesn't even remotely look as promising as the results from.the denver study.

I wish I had the answers to your questions. I can’t figure out why they left out some of the mutations from the Denver study or why they chose to limit the inclusion criteria to specific mutations instead of also including those that had clinical evidence of residual function like you. The study is finally closed and March 2017 is when they are projecting the final collection date for primary outcome measure. I’m not sure what the timeline will be after this. Hopefully, data is analyzed quickly and FDA passes. I’m not sure if they will pass for those not heterozygous for F508del. I’m hoping they will, theorizing that since F508del doesn’t respond to Kalydeco, those in study that responded to Kalydeco alone were responsive because of their one residual function mutation. (there were 2 arms in study- comparing Kalydeco alone with 661+Kalydeco). Hoping they will include those with clinical evidence of residual function, but unfortunately, I think this is unlikely since that’s not how study was designed. So sad that those that have the potential to benefit, but don’t have specific mutations included, may not even have the chance to try.
If I hear anything further, I’ll be sure to let you know.
 

MissMe

New member
I wish I had the answers to your questions. I can’t figure out why they left out some of the mutations from the Denver study or why they chose to limit the inclusion criteria to specific mutations instead of also including those that had clinical evidence of residual function like you. The study is finally closed and March 2017 is when they are projecting the final collection date for primary outcome measure. I’m not sure what the timeline will be after this. Hopefully, data is analyzed quickly and FDA passes. I’m not sure if they will pass for those not heterozygous for F508del. I’m hoping they will, theorizing that since F508del doesn’t respond to Kalydeco, those in study that responded to Kalydeco alone were responsive because of their one residual function mutation. (there were 2 arms in study- comparing Kalydeco alone with 661+Kalydeco). Hoping they will include those with clinical evidence of residual function, but unfortunately, I think this is unlikely since that’s not how study was designed. So sad that those that have the potential to benefit, but don’t have specific mutations included, may not even have the chance to try.
If I hear anything further, I’ll be sure to let you know.
Thanks for your reply! I have an appointment with one of the senior doctors at my clinic soon, one.of wery few who actualy knows anything about new therapies. I hope she isn't prevented from saying what she knows, if she knows.something. I contacted Vertex naively thinking they would answer my questions but they told me they couldn't say anything but my doctor could get in touch with them if they had questions.
 

stephen

Super Moderator
missme and others,

I know it can be extremely frustrating contacting Vertex about Kalydeco (and probably Orkambi) if you are not taking it On-label. I’ve tried a number of times. They will not even discuss information that is public knowledge.

As you mentioned, getting Kalydeco is not an option in Sweden where you live. That’s unfortunate.

For those in the US with Residual Function Mutations who may have been unsuccessful in getting Kalydeco Off-label, there is an excellent cover article in the Summer 2016 issue of CF Roundtable titled "The Option Of Off-label Kalydeco".

http://www.cfroundtable.com/online-newsletters/summer-2016-newsletter/#jump1

The article has a lot of great information. If your doctor has been reluctant to prescribe it, I highly recommend you take a copy to your next CF Center visit.


PS: It’s nice to be back to a familiar Cysticfibrosis.com forum format.
 
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MissMe

New member
missme and others,

I know it can be extremely frustrating contacting Vertex about Kalydeco (and probably Orkambi) if you are not taking it On-label. I’ve tried a number of times. They will not even discuss information that is public knowledge.

As you mentioned, getting Kalydeco is not an option in Sweden where you live. That’s unfortunate.

For those in the US with Residual Function Mutations who may have been unsuccessful in getting Kalydeco Off-label, there is an excellent cover article in the Summer 2016 issue of CF Roundtable titled "The Option Of Off-label Kalydeco".

http://www.cfroundtable.com/online-newsletters/summer-2016-newsletter/#jump1

The article has a lot of great information. If your doctor has been reluctant to prescribe it, I highly recommend you take a copy to your next CF Center visit.


PS: It’s nice to be back to a familiar Cysticfibrosis.com forum format.

Great article! I appreciate so much the efforts you, jricci and others are doing to try and help others in accessing Kalydeco!

I see you have an x-mutation like me and that gives me hope that the x-mutation on one allele shouldn't automatically mean that Kalydeco wouldn't work on the other. Are you also pancreatic sufficient?
 
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