Kalydeco and Class IV Mutations

[Aboveallislove]

Autumn,

Two other thoughts: If you fit the inclusion criteria, and since you don't now have Kalydeco, I wonder if you would actually be better getting in the 661 study than trying to now get Kalydeco off label because you will continue with 661 open label after (I THINK...I'd confirm this though to make a decision). It could take you a few months to get Kalydeco off label (between doctor, insurance, etc.) and if they are recruiting and starting soon, you could get the combo in the study near same time. And the combo should work even better for you given the results of the combo for those Kalydeco benefits alone.
OR, I wonder if it makes more sense to try to get the 809/Kalydeco combo off label when it comes out which should do the same as 661/Kalydeco??? For those on Kalydeco now I would be pushing to go to 809/Kalydeco when it comes out given results of 661/Kalydeco study.

 

[triples15]

Autumn,

Two other thoughts: If you fit the inclusion criteria, and since you don't now have Kalydeco, I wonder if you would actually be better getting in the 661 study than trying to now get Kalydeco off label because you will continue with 661 open label after (I THINK...I'd confirm this though to make a decision). It could take you a few months to get Kalydeco off label (between doctor, insurance, etc.) and if they are recruiting and starting soon, you could get the combo in the study near same time. And the combo should work even better for you given the results of the combo for those Kalydeco benefits alone.
OR, I wonder if it makes more sense to try to get the 809/Kalydeco combo off label when it comes out which should do the same as 661/Kalydeco??? For those on Kalydeco now I would be pushing to go to 809/Kalydeco when it comes out given results of 661/Kalydeco study.

I've had absolutely the same thoughts! The Denver trial had a 2 year open label, and from what I've heard, most (if not all) of the Vertex trials have at least some open label period. It would be amazing to be getting the drug for free as well!! I have concerns, as I've heard many others do, about our insurance policy being billed such high prices. I know that legally employers can't fire someone due to health/insurance issues, but I also wasn't born yesterday, so I know it *can* happen. My husband is in the oil industry which is laying off people en mass right now due to low oil prices. Would hate to give them a reason to target my husband. So anywho, yes, I think the trial may be a good bet. I plan to try to get in touch with the research coordinators prior to my April 16th CF appointment. If getting into the study isn't a possibility or sounds unlikely, I'll try getting a script again. Altho I'm seeing the NP again, so we'll see.

Oh, also wanted to mention, the way I understand it (and once again I could be wrong) is that this study has an arm that is Kalydeco monotherapy. So I may not necessarily get the combo.

Thanks again!

Autumn

 

[Aboveallislove]

Hey Autumn,
You are absolutely right (I hadn't realized that) that they have a separate arm with only Kalydeco. Throwing out a few more thoughts which I'm sure you've considered, but in case others aren't as familiar. I totally agree re trying the study as a first option because the insurance process could be months and months of fighting. But I looked at the study and as opposed to the homozygous arm it doesn’t say "open label," so you might want to inquire on that to see if they will have that as an option after. But even if the answer is no, I do think you would be better off because if you get the drug and it isn’t open label after, you’ll have more evidence to support an off label script for Kalydeco and 809/Kalydeco. Another thought and from a selfish point of view (albeit not selfish for me but for other Cfers), if you qualify as a residual function but the in vitro shows that Kalydeco alone works really well for your mutations you will help the mean be higher for everyone and thus have it labeled more broadly for all residual function mutations. In other words, if some residual function mutations only benefit 2% but you 12% it will pull the mean up and then it could get approval for a broader class of Cfers.

I sent you an email your other account too; and if you want to send me the relevant language from your insurance contract I’ll see if I can translate any lawyeresse that might be confusing.

 

[jricci]

Just wanted to give an update. Unfortunately I didn’t get very far. I called both Vertex and CFF and neither were able to provide any more information regarding the inclusion criteria for the VX-661 study for residual function mutations. The person I spoke with at Vertex said he thought the specifics weren’t outlined because the study isn’t recruiting participants yet. He thought more information would be available in the next couple of weeks; but didn’t give me any indication as to when the study would officially be opened for enrollment.
If anyone does decide to go the insurance route and needs medical literature to back up their appeal, I suggest you contact the CF Foundation’s Patient Assistance Resource Center. I forwarded them some journal articles that may be helpful. They aren’t able to promote off label use, but they can provide information to those calling in and requesting help with insurance appeals. Also, my doctor is working together with other doctors on getting an article published regarding their experiences with Kalydeco and off label use for residual function mutations. I’ll make sure I post as soon as I know when the article is expected to be published.

 

[triples15]

Just wanted to give an update. Unfortunately I didn’t get very far. I called both Vertex and CFF and neither were able to provide any more information regarding the inclusion criteria for the VX-661 study for residual function mutations. The person I spoke with at Vertex said he thought the specifics weren’t outlined because the study isn’t recruiting participants yet. He thought more information would be available in the next couple of weeks; but didn’t give me any indication as to when the study would officially be opened for enrollment.
If anyone does decide to go the insurance route and needs medical literature to back up their appeal, I suggest you contact the CF Foundation’s Patient Assistance Resource Center. I forwarded them some journal articles that may be helpful. They aren’t able to promote off label use, but they can provide information to those calling in and requesting help with insurance appeals. Also, my doctor is working together with other doctors on getting an article published regarding their experiences with Kalydeco and off label use for residual function mutations. I’ll make sure I post as soon as I know when the article is expected to be published.

Thanks so much for the update! It's so goofy because the study was updated to say "enrolling" as of last week on the clinicaltrials.gov site. Given that, I'm surprised at the lack of information everyone seems to have. I did email the coordinators and Houston and Dallas and heard back from both. Yay for that! However, Houston said that they are pretty sure, but not certain, that they are participating and they they are no where near screening people yet. Huh. Dallas sounded more promising and said they are for sure participating and most likely I could be screened and requested my medical records. Whoo hoo! They said they are still a couple months from starting the screening process though. As I said, I'm just surprised at the lack of information anyone has given the status online. Oh well, patience patience. Lol.

That is just SO awesome that your doctor (and others) are working on publishing an article regarding off label use for residual function mutations! The more evidence the better! I appreciate that so so much. Really I do. If I don't get into this study I will be checking into the journal articles you mentioned. They may be the ones I have already, but if they are new that would be awesome.

Thank a bunch again,

Autumn

 

[jricci]

Thanks so much for the update! It's so goofy because the study was updated to say "enrolling" as of last week on the clinicaltrials.gov site. Given that, I'm surprised at the lack of information everyone seems to have. I did email the coordinators and Houston and Dallas and heard back from both. Yay for that! However, Houston said that they are pretty sure, but not certain, that they are participating and they they are no where near screening people yet. Huh. Dallas sounded more promising and said they are for sure participating and most likely I could be screened and requested my medical records. Whoo hoo! They said they are still a couple months from starting the screening process though. As I said, I'm just surprised at the lack of information anyone has given the status online. Oh well, patience patience. Lol.

That is just SO awesome that your doctor (and others) are working on publishing an article regarding off label use for residual function mutations! The more evidence the better! I appreciate that so so much. Really I do. If I don't get into this study I will be checking into the journal articles you mentioned. They may be the ones I have already, but if they are new that would be awesome.

Thank a bunch again,

Autumn

Autumn, yes, you have it right. I just looked it up on the clinicaltrials.gov site. It is listed as enrolling. It’s very strange that the representative at Vertex didn’t know this. He even asked me for the clinical trial number and looked it up in their system. This was on Friday. The clinicaltrial.gov site states that the trial’s enrollment status was updated from not enrolling to enrolling on April 5[SUP]th[/SUP]. I’ll try calling them again, now knowing that it is in fact enrolling. They must have specifics at this point. I just have to find the right person to talk to.

There is someone else that I was in contact with that is also interested in participating in the study and she was told that it will be open label after completion. I know with the Denver trial, it didn’t state open label in the beginning. It was added after the start of the study.

I’m so glad to hear that you are getting a response from Dallas. Keep up the persistence. Believe me-it will be worth it!

 

[triples15]

Autumn, yes, you have it right. I just looked it up on the clinicaltrials.gov site. It is listed as enrolling. It’s very strange that the representative at Vertex didn’t know this. He even asked me for the clinical trial number and looked it up in their system. This was on Friday. The clinicaltrial.gov site states that the trial’s enrollment status was updated from not enrolling to enrolling on April 5[SUP]th[/SUP]. I’ll try calling them again, now knowing that it is in fact enrolling. They must have specifics at this point. I just have to find the right person to talk to.

There is someone else that I was in contact with that is also interested in participating in the study and she was told that it will be open label after completion. I know with the Denver trial, it didn’t state open label in the beginning. It was added after the start of the study.

I’m so glad to hear that you are getting a response from Dallas. Keep up the persistence. Believe me-it will be worth it!

Yes it's so weird that they don't much being as it says "enrolling" as of April 5th as you said. Do let us know what they say when you call them back!

The coordinator in Dallas just told me that they don't know yet whether there will be an open label period or not. So I'm hoping that the person you talked to is right in saying that there is. I'm going to assume they are because it seems like almost all (or all?) the Vertex trials have had one.

She said that they will reimburse me for travel, so that is excellent.

For now that's about all I know. She said she'll keep in contact with me and give me more details as they get them. Also she said she'll send me the consent form when they have one. So now I wait.

Thanks again Jricci! I really appreciate all of your help, and I will remain persistant. I'm usually not a super assertive person, but hey, when it comes down to my LIFE that we're talking about I can be!

Talk to you soon!

Autumn

 

[jricci]

I found out some information, but still don't know how "residual function" will be defined. According to one of the research nurses that is involved with this study, it will be difficult to get into this particular study if your CF center is not participating because the enrollment is limited to 100 people in the United States. The trial says they are enrolling 300, but this is worldwide. I have not seen any of this in writing. This is just as per a conversation I had with a research nurse. Centers will start filling spots with those eligible from their center and if spots are still available, they will accept people from other centers. Vertex will compensate for travel, according to the person I spoke with.
Given this information, I would call as many centers that are feasible for you to travel to and give them your information, including medical records (i.e. your mutation, evidence of pancreatic function, sweat chloride value), so that they will contact you if their clinic’s enrollment is not complete.

Also, I found out that those who culture Mycobacterium, Burkholderia cepacia, or Burkholderia dolosa will be excluded.
I'll post as I find out more.

 

[lifeisgood729]

From Facebook this morning:

Our clinic is going to be doing the 661- Ivacaftor study for residual function, starting this summer. At Stanford / LPCH in California. Woohoo!
Got some paperwork on the trial today. Interesting lay out, it's a 32 week study. 4 wks pre study drug screening, 8 weeks on drug, 8 wks washout. 8 wks on drug 4 wk post study screening.
There are 6 different senario, 8 weeks on 8 weeks off 8 wks on a different combo.
These are the sequences you will randomly be place in one.
1. 8 wks 661w/ Ivacaftor (washout 8wks) 8 wks ivacaftor
2. 8 wks Ivacaftor (washout 8 wks). 8 wks 661/ Ivacaftor
3. 8 wks 661/Ivacaftor (washout 8 wks) 8 wks placebo
4. 8 wks Placebo (washout 8 wks) 8 wks 661/Ivacaftor
5. 8 wks Ivacaftor (washout 8 wks) 8 wks placebo
6. 8 wks placebo (washout 8 wks) 8 wks Ivacaftor.
Depending on the results, if they are good there will be an extension for everyone on drugs

 

[jricci]

Just talked to another study nurse. Even though she has the list, she can’t give it to me. What I did find out is that they are going by genotype only, not phenotype (pancreatic sufficiency). She did inform me that my mutation is not listed (r334w) I’m a class IV conductance mutation so there goes the theory that all class IV and V mutations may be included. This is so frustrating for me to hear. I wish there was some way that they were able to officially collect data from off-label use. So I guess what this implies is that when this drug is eventually approved for residual function mutations (because I’m pretty certain it will be!), people with my mutation won’t be eligible. This is heart breaking because I’m living proof that it works! You would think I’d offer more proof than what happens in vitro!

 

[Aboveallislove]

Hey jricci,
I am so sorry. I hope that isn't accurate and she is just misinformed. That really stinks. :-(. But if it is true, remember there is another arm just for heteros who aren't suppose to benefit from Kalydeco. I'd think if they don't list your mutation for residual function then you would fit that other arm.
Also, I'm sorry if you've said in other posts, but have your tried to get off label? PM me if you want more info on that. Hugs and prayers,
Love

 

[triples15]

From Facebook this morning:

Our clinic is going to be doing the 661- Ivacaftor study for residual function, starting this summer. At Stanford / LPCH in California. Woohoo!
Got some paperwork on the trial today. Interesting lay out, it's a 32 week study. 4 wks pre study drug screening, 8 weeks on drug, 8 wks washout. 8 wks on drug 4 wk post study screening.
There are 6 different senario, 8 weeks on 8 weeks off 8 wks on a different combo.
These are the sequences you will randomly be place in one.
1. 8 wks 661w/ Ivacaftor (washout 8wks) 8 wks ivacaftor
2. 8 wks Ivacaftor (washout 8 wks). 8 wks 661/ Ivacaftor
3. 8 wks 661/Ivacaftor (washout 8 wks) 8 wks placebo
4. 8 wks Placebo (washout 8 wks) 8 wks 661/Ivacaftor
5. 8 wks Ivacaftor (washout 8 wks) 8 wks placebo
6. 8 wks placebo (washout 8 wks) 8 wks Ivacaftor.
Depending on the results, if they are good there will be an extension for everyone on drugs

Thanks Martha! Looks a lot like Denver. Except Denver was 4 weeks on placebo or drug, then 4 week washout, then 4 weeks on placebo or drug etc... I think it was 26 weeks. There was of course, no 661 though..

 

[triples15]

I found out some information, but still don't know how "residual function" will be defined. According to one of the research nurses that is involved with this study, it will be difficult to get into this particular study if your CF center is not participating because the enrollment is limited to 100 people in the United States. The trial says they are enrolling 300, but this is worldwide. I have not seen any of this in writing. This is just as per a conversation I had with a research nurse. Centers will start filling spots with those eligible from their center and if spots are still available, they will accept people from other centers. Vertex will compensate for travel, according to the person I spoke with.
Given this information, I would call as many centers that are feasible for you to travel to and give them your information, including medical records (i.e. your mutation, evidence of pancreatic function, sweat chloride value), so that they will contact you if their clinic’s enrollment is not complete.

Also, I found out that those who culture Mycobacterium, Burkholderia cepacia, or Burkholderia dolosa will be excluded.
I'll post as I find out more.

Wow, that's a bummer for me to hear that it will probably be hard to get into. I've contacted Houston and Dallas, the only other feasible center would be Tyler so maybe I'll contact them to.

It's also a bummer to hear they are going straight off the residual function list. I, like others, had hoped it would be a bit more broad. I am lucky in that I still qualify based on my mutation, but bummed for others.

Well, thanks for the info and the update!

Autumn

 

[jricci]

Hey jricci,
I am so sorry. I hope that isn't accurate and she is just misinformed. That really stinks. :-(. But if it is true, remember there is another arm just for heteros who aren't suppose to benefit from Kalydeco. I'd think if they don't list your mutation for residual function then you would fit that other arm.
Also, I'm sorry if you've said in other posts, but have your tried to get off label? PM me if you want more info on that. Hugs and prayers,
Love

Thanks aboveallislove,
I am one of the lucky ones that is receiving it off-label. Kalydeco alone has done wonders. I wasn't trying to get into the 661 study at this time. I'm just so upset for the other 163 people that share my mutation because once the study is done and it is officially approved (hopefully!)., my mutation wouldn't be included as one of the approved mutations.

 

[Aboveallislove]

Oh, I'm so glad you are, but I agree...it is horrible for those who can't get! I can't keep everyone straight, but is your doctor the one doing the case study? That could help them. Also, if they all tried to get in the "hetero" arm (non residual mutation arm), they could really scew the results favorably since they will all be benefiting from your mutation and could get it available for all heteros! (because I really think the mutation is only part of it and as Jenny's pictures show, it helps those even it wasn't "suppose" to help!!). As an aside, are you going to try to get 809/combo when it's approved since 809 and 661 work the same way?

 

[jricci]

Oh, I'm so glad you are, but I agree...it is horrible for those who can't get! I can't keep everyone straight, but is your doctor the one doing the case study? That could help them. Also, if they all tried to get in the "hetero" arm (non residual mutation arm), they could really scew the results favorably since they will all be benefiting from your mutation and could get it available for all heteros! (because I really think the mutation is only part of it and as Jenny's pictures show, it helps those even it wasn't "suppose" to help!!). As an aside, are you going to try to get 809/combo when it's approved since 809 and 661 work the same way?

Sorry, you lost me on the 661 study. What arm are you talking about? Is it a current study or one that is expected soon?
To answer your other question, I’ll probably just stay with the Kalydeco. I still have this fear that my insurance covered this inadvertently since there were no questions asked, no appeals necessary. I literally feel nauseas whenever there’s a letter from my insurance company addressed to me. I’m so worried that they are telling me that there’s been an oversight and it should have never been approved. I wouldn’t want to bring it to their attention by trying to get VX-809 off label (when it does get approved for ddf508). I’m so thankful for Kalydeco, I don't want to press my luck.

 

[Aboveallislove]

Sorry. There are eventually going to be 4 arms. There will be one arm that is for heterozygotes with df508 and another mutation not know to be benefited by Kalydeco. So, to me, it would seem they would qualify any df508 heterozygotes who don't qualify for the residual function arm criteria. And if those who likely would benefit from Kalydeco "qualify" and enroll that could get better results overall and maybe help make the labeling such that all heterozygotes with df508 qualify. Hope that makes more sense.

Totally understand re the under the radar. I'd do the same!!!!

Sorry, you lost me on the 661 study. What arm are you talking about? Is it a current study or one that is expected soon?
To answer your other question, I’ll probably just stay with the Kalydeco. I still have this fear that my insurance covered this inadvertently since there were no questions asked, no appeals necessary. I literally feel nauseas whenever there’s a letter from my insurance company addressed to me. I’m so worried that they are telling me that there’s been an oversight and it should have never been approved. I wouldn’t want to bring it to their attention by trying to get VX-809 off label (when it does get approved for ddf508). I’m so thankful for Kalydeco, I don't want to press my luck.

 

[jricci]

I received some more information re: 661 study (108) for residual function https://clinicaltrials.gov/ct2/show/NCT02392234 I spoke with the study nurse coordinator from Tucson AZ CF center (pediatric and adult). She was very helpful and said that although she can’t share the mutations that are listed as inclusive for the study, if someone would like to find out if their mutation is listed, you can contact her and she will answer your question directly. The Tucson AZ center and the Tampa FL center are the only 2 centers that are currently accepting participants for this particular study. She said that the general guideline that Vertex has set is that each participating center can accept 3 patients. Because the Tucson center is one of only 2 centers currently enrolling, they have been granted permission to accept more participants beyond the 3 originally stated and they are currently accepting inquires from those patients from other centers. She said that Vertex will be activating 12 more centers in the US sometime in May. She also said that there is an upcoming VX-661 study (109) that will be broader in their inclusion. https://clinicaltrials.gov/ct2/show/NCT02412111
This isn’t real clear to me because it looks like it will be for those patients with gating mutations, but maybe I’m missing something. She also said that Vertex’s reimbursement for travel for the 661 studies would be very limited because the need for participants isn’t an issue. She thought that they would reimburse patients up to $250.00. I’m not sure if this is a total for the entire span of the study or per study visit. So if anyone is interested in this 661 study for residual function (108 ) and is from the Tucson area and/or is willing to travel there, I would encourage you to contact her. Her contact information (from CFF website) is Molina de Rodriguez: omolina@email.arizona.edu
Her phone number is (520) 891-6767 (also listed from the CFF website) Please note that this phone number is her work cell number so please take the time zone difference into account when you call her.

 

[Aboveallislove]

Thanks so much for posting! I'm wondering if she means the more general heterozygote study I mention above. There will be 4 studies in total. This summarizes the different studies. One is the residual function and one the gating ones and then ddf508 and then a heterozygote df508.
http://investors.vrtx.com/releasedetail.cfm?ReleaseID=902790