Kalydeco and Class IV Mutations

[stephen]

jricci,


Welcome to the “Club”! I love to hear when others with a Class 4 Residual Function mutation do so well with Kalydeco.

Your experience with Kalydeco mirrors mine - except I started seeing the effects in less than a day. In a week, my cough was completely gone, and so was all the green crap. Hopefully you too will have the same experience.

I just started my ninth month on Kalydeco. There is no more cough or the need for antibiotics so far. My wife of 49 years keeps mentioning the dramatic effect Kalydeco has had.

I have lost some of the large gain in FEV1 I experienced in the first two months. This may very well be due to my reduced use of drugs such as Advair and Spiriva, which I no longer use at all. Since I feel so great thank G-d, the loss of some of the FEV1 gain that I experienced is worth not having to be concerned about the side effects these drugs can have.

I have contacted Vertex, the FDA, and previous CF doctors I’ve seen to let them know of my experiences with Kalydeco. The doctors informed me that they too have patients like me who are getting Kalydeco now. Hopefully it will not be too long before all CFers get Kalydeco, or some other drug, and experience dramatic improvements.

It absolutely mystifies why ALL CF doctors in the US, don’t try to get Kalydeco NOW for their patients who have a “Residual Function” mutation. Insurance coverage is another issue - but the doctors should at least try!

 

[ladybird]

Hi Jricci!

Congratulations. I have R117C and DeltaF508 and am waiting to get insurance approval for kalydeco. I got my doctors to write a prescription after Stephen on this forum spread the news about how much it has improved him.

I did some research on the law and according to CA HEALTH AND SAFETY CODE 1367.21.
I can get the drug if certain requirements are met, including the following critical ones (for my purposes)

(3) The drug has been recognized for treatment of that condition by any of the following:

(A) The American Hospital Formulary Service’s Drug Information.
...
(C) Two articles from major peer reviewed medical journals that present data supporting the proposed off-label use or uses as generally safe and effective unless there is clear and convincing contradictory evidence presented in a major peer reviewed medical journal.

(b) It shall be the responsibility of the participating prescriber to submit to the plan documentation supporting compliance with the requirements of subdivision (a), if requested by the plan.
...
(g) Nothing in this section shall be construed to prohibit the use of a formulary, copayment, technology assessment panel, or similar mechanism as a means for appropriately controlling the utilization of a drug that is prescribed for a use that is different from the use for which that drug has been approved for marketing by the FDA.

(h) If a plan denies coverage pursuant to this section on the basis that its use is experimental or investigational, that decision is subject to review under Section 1370.4.

(i) Health care service plan contracts for the delivery of Medi-Cal services under the Waxman-Duffy Prepaid Health Plan Act (Chapter 8 (commencing with Section 14200) of Part 3 of Division 9 of the Welfare and Institutions Code) are exempt from the requirements of this section.
(Amended by Stats. 2009, Ch. 479, Sec. 1. Effective January 1, 2010.)

For those interested, the full text is available at http://leginfo.legislature.ca.gov/faces/codes_displaySection.xhtml?lawCode=HSC&sectionNum=1370.4.
So insurers, in CA at least are not approving this out of the goodness of their hearts. When I first read Stephen's posts I was amazed that exclusion-focused insurance companies that would cover anything off-label. But this (and similar laws in other states) explains it. The following web-site is designed for cancer-patients looking for support for off-label drugs but may be helpful to anyone looking for a starting point for their state's off-label drug coverage law. http://www.scld-nci.net/linkdocs/products/datatables116.pdf

 

[jricci]

Aboveallislove-Yes, I will mention to my doctor about writing up a case study to be published. I have a sweat test scheduled for the beginning of December. I have absolutely no doubt that these results will further support the use of Kalydeco for my mutation/residual mutations. I’ll be sure to post the results as soon as I get them.

Autumn- I would definitely keep pushing your doctor. I’m willing to share my medical records if any doctor would like to see them. A week ago, if you told me that I would feel like I do today, I wouldn’t believe it. I think because I had such severe inflammation for so many years, my response has been quick and dramatic. If inflammation is controlled, some lung function can be regained. My doctor always hoped that one of the big reasons for my very low lung function was because of a lot of inflammation as opposed to mostly structural damage. It looks like he was right. I’ve had wheezing/tight airways for about 3 years straight. I have no wheezing whatsoever right now.

Stephen- thanks for sharing your story. I really think we have to find a way to have patient’s off label experiences officially documented somehow so that they are centrally located and easily accessible to doctors and patients. Although, thankfully, it seems as though the FDA is pushing these studies through pretty quickly so hopefully everyone who can benefit from this drug will be able to do so soon.

Ladybird-thanks for sharing all of this information. Good luck to you and I hope your insurance covers it quickly without any appeals necessary. Be sure to keep us updated.

 

[triples15]

Hi again everyone! Just keeping this post alive....

The Phase 3 trial for Kalydeco/661 in subjects with DF508 and a residual function mutation has been posted to the clinicaltrials.gov site. You can read it here:

https://clinicaltrials.gov/ct2/show/study/NCT02392234?term=Ivacaftor+661&rank=1&show_locs=Y#locn

My center isn't participating, but others in my state (Texas) are. It looks like the criteria to get in are more lax than the phase 2 (the n of 1 in Denver that I was screened for), and I stand a decent shot of getting in this one. I know preference will, of course, be given to patients who are seen are these clinics, but I'm hoping to get in touch with the research coordinators so they can keep me in mind if they do not have enough patients with residual function mutations who want to participate.

So on that note, if anyone goes to clinic in Houston or Dallas and have the contact info for the research coordinator (s) I would be so grateful! I'm still just trying to get my hands on Kalydeco any way possible!

Thanks a bunch, and take care everyone!

Autumn 34 w/CF

 

[Aboveallislove]

Good Luck Autumn!
I don't see the criteria for "residual function" though. Can you point them out for others? I know before there were three (PS, less than something for SC, or certain mutations), but don't see now.
Thanks!

 

[triples15]

Good Luck Autumn!
I don't see the criteria for "residual function" though. Can you point them out for others? I know before there were three (PS, less than something for SC, or certain mutations), but don't see now.
Thanks!

Thanks Love!

I don't see any specific criteria for "residual function" either. In the Denver trial those criteria that you are referencing were listed under the "inclusion criteria". For Denver you had to have a sweat test UNDER 80. This one says a sweat test OVER 60 (or documented evidence of chronic sinopulmonary disease). They also looked at fecal elastase numbers for Denver (I believe it had to be over 200 if memory serves), and no mention of that in the criteria here. The language used for this one "and a Second Allele With a CFTR Mutation PREDICTED to Have Residual Function" leads me to believe that perhaps they are going to go directly off the list of residual function mutations, rather than looking at phenotype. This is just a guess on my part though, so if anyone has anything concrete or other theories, I'd love to hear it.

If anyone is curious, the following are what are considered "Residual function" 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

Autumn

 

[Aboveallislove]

I'm hoping they go broader than just the listed mutations because there have to be so many with residual function that are one offs. I forget, do you have a listed mutation? I really hope you can get in this now because the 661 combo should get you even better than Kalydeco....soooo close. Do keep us posted!

 

[triples15]

I'm hoping they go broader than just the listed mutations because there have to be so many with residual function that are one offs. I forget, do you have a listed mutation? I really hope you can get in this now because the 661 combo should get you even better than Kalydeco....soooo close. Do keep us posted!

Yes, I have S945L. In the Van Goor documents it's shown to respond very well to Kalydeco alone. It has been super frustrating for me to sit back and wait with the evidence that is already out there, but alas, we have no other choice.

It will be interesting to hear exactly how they are qualifying "residual function" for the purpose of this study. Hopefully someone with inside knowledge will chime in, or I will definitely update if/when I am able to get a hold of the research coordinators. I'm going to wait a bit to try to contact them because a fellow CFer contacted one of the centers listed as participating and they didn't know what he was talking about! Ugh. So I'll give them a bit of a chance to figure out what's going on and then try to get in touch.

 

[jricci]

Hi Autumn
Sounds like you never had any luck with convincing your new doctor to order Kalydeco? I'm sorry to hear this. But it would be great if you could get in this study. I'm not from Texas but this is some contact info. I gathered from the TX care centers participating in the study:

Houston
Carolyn Wheeler, RN, Clinical Research Coordinator, (713) 798-2687

Tyler-
Study Coordinator: Rebekah Hibbard
Phone: (903)877-8246
Rebekah.Hibbard@uthct.edu

University of Texas Southwestern Medical Center/ St. Paul University Hospital (Adult), Dallas, TX, 75390

Contact Information:
 Keller, Ashley
 Phone: (214) 648-2817
 Email: Ashley.Keller@UTSouthwestern.edu

I'll contact my research nurse tomorrow and ask about how the study is defining residual function mutations. I'll keep you updated.
I know you've been trying to get your hands on this drug for years and like me, you weren't able to participate in the Denver trial 2 years ago. It must be so frustrating for you knowing that there is something out there that has a very high probability of helping you and you're not able to get it prescribed. Because I've had such a positive response, it makes me even more motivated to help others with residual function mutations gain access to it. I hope it all works out for you. You'll be in my thoughts.



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[jricci]

Hi Autumn
Sounds like you never had any luck with convincing your new doctor to order Kalydeco? I'm sorry to hear this. But it would be great if you could get in this study. I'm not from Texas but this is some contact info. I gathered from the TX care centers participating in the study:

Houston
Carolyn Wheeler, RN, Clinical Research Coordinator, (713) 798-2687

Tyler-
Study Coordinator: Rebekah Hibbard
Phone: (903)877-8246
Rebekah.Hibbard@uthct.edu

University of Texas Southwestern Medical Center/ St. Paul University Hospital (Adult), Dallas, TX, 75390

Contact Information:
 Keller, Ashley
 Phone: (214) 648-2817
 Email: Ashley.Keller@UTSouthwestern.edu

I'll contact my research nurse tomorrow and ask about how the study is defining residual function mutations. I'll keep you updated.
I know you've been trying to get your hands on this drug for years and like me, you weren't able to participate in the Denver trial 2 years ago. It must be so frustrating for you knowing that there is something out there that has a very high probability of helping you and you're not able to get it prescribed. Because I've had such a positive response, it makes me even more motivated to help those with residual function mutations gain access to it. I hope it all works out for you. You'll be in my thoughts.



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[stephen]

Triples, and others with Residual Function mutations;

You DO have a choice. Try to get your doctor to prescribe Kalydeco now.

A year ago my doctor did - based on me having D1152H. It's been a life changer!

If your doctor won't prescribe it now, unless he/she has a better reason than just "it's not on the list", I strongly recommend trying another CF center. I do realize that just because your doctor prescribes it, you may not be able to get it - but at least try!

 

[triples15]

Triples, and others with Residual Function mutations;

You DO have a choice. Try to get your doctor to prescribe Kalydeco now.

A year ago my doctor did - based on me having D1152H. It's been a life changer!

If your doctor won't prescribe it now, unless he/she has a better reason than just "it's not on the list", I strongly recommend trying another CF center. I do realize that just because your doctor prescribes it, you may not be able to get it - but at least try!

Thanks Stephen! I totally agree. I'm glad your doctor is open-minded and was willing to try. It's beyond awesome that you are on Kalydeco.

Unfortunately, I have tried to get my doc to prescribe it. In fact, I'm on my second clinic and still being told no. I didn't just go in there all willy nilly and say "hey, I wanna try Kalydeco!" either. I went armed with lots of info, showing how it's predicted to work with my specific residual function mutation. It's frustrating to say the least. The only silver lining is that at my new clinic the only person I've talked to about it is the NP, because that's who I saw at my last appoinment. Unfortunately, I will not see the doc again at my next appointment because I had to reschedule, and therefore now have to see the NP. I do intend to put the full-court press on this doctor, as I did my last one.

At my last clinic, my doc's point of view was "we're not prescribing it off-label. Insurance won't pay for it, and you're in a good position to wait". Ummmm, okay. I think the whole "position to wait" thing is because, outside of exacerbations here and there, my lung function has maintained close to the same baseline for a decade or so. Still, trust me, I do not feel like I should be waiting. At the new clinic, I was simply told by the NP that "insurance just won't pay for it". Once again (and I feel like I banging my head against a brick wall here), but what in the world does it hurt to TRY? So you're tellling me my insurance is going to deny it, perfect, let's try it and see!! Grrrr....

So at this point, I feel like my best (or only) option is to try to get into the study. We'll see. As I said, when I do see the doctor next at my new clinic I fully intend to press hard.

Autumn 34 w/CF

 

[triples15]

Hi Autumn
Sounds like you never had any luck with convincing your new doctor to order Kalydeco? I'm sorry to hear this. But it would be great if you could get in this study. I'm not from Texas but this is some contact info. I gathered from the TX care centers participating in the study:

Houston
Carolyn Wheeler, RN, Clinical Research Coordinator, (713) 798-2687

Tyler-
Study Coordinator: Rebekah Hibbard
Phone: (903)877-8246
Rebekah.Hibbard@uthct.edu

University of Texas Southwestern Medical Center/ St. Paul University Hospital (Adult), Dallas, TX, 75390

Contact Information:
 Keller, Ashley
 Phone: (214) 648-2817
 Email: Ashley.Keller@UTSouthwestern.edu

I'll contact my research nurse tomorrow and ask about how the study is defining residual function mutations. I'll keep you updated.
I know you've been trying to get your hands on this drug for years and like me, you weren't able to participate in the Denver trial 2 years ago. It must be so frustrating for you knowing that there is something out there that has a very high probability of helping you and you're not able to get it prescribed. Because I've had such a positive response, it makes me even more motivated to help others with residual function mutations gain access to it. I hope it all works out for you. You'll be in my thoughts.

Thank you so much J! I really appreciate your response so much. It is indeed frustrating, and I feel like my anger/frustration is becoming more evident in these posts.

I don't want to sound like a broken record (as if I don't already), so my story about the doctor's saying no is in my response to Stephen. Long story short, no one has agreed to prescribe it yet.

Thanks so much for finding the contact info for me. That was beyond kind of you.

Do let us know what you are able to find out when you talk to the research nurse at your clinic! Thanks for offering!

Autumn

 

[Aboveallislove]

Hey Autumn,
I'm not sure if I mentioned this, if so, sorry, not trying to be a nag! But in preparation for your meeting with the doctor to request off label, I'd print off your insurance plans coverage for "experimental" or "off label." Most policies provide that it is covered if there is certain types of evidence and with your mutation there is. Also, under FDA regs, your doctor can request info directly from Vertex re any evidence it has that it works on your mutations.

 

[stephen]

As I’ve previously mentioned, my CF doctor has prescribed Kalydeco for a number of patients who have Residual Function mutations. (I don’t know just how many.)

Some fortunate patients, myself included, got Kalydeco without any real problems from their insurance provider. For others, it took some effort on the part of my doctor and/or other CF center personnel to “convince” the insurance provider before the Kalydeco was approved. There were also cases where the Kalydeco was never approved. (Again, I don’t have numbers or percentages.)

All of the patients who got Kalydeco did show improvement, through not all to the same degree. The improvements applied pulmonary issues only. Improvements in digestive and sinus issues were very questionable.

If I recall correctly, my doctor is collaborating with another CF center to publish their experiences with Kalydeco and patients having Residual Function mutations.

I found the comment by Abovealislove very interesting where she stated that doctors can request information from Vertex regarding Kalydeco working on other mutations. On more than one occasion, I’ve contacted Vertex directly to let them know how well Kalydeco is working for me. I think I’ll call them again.

While I’m not trying to stir up a hornet’s nest, it’s hard to understand why some doctors are so reluctant to try getting Kalydeco for patients it could help. Yes, for patients who don’t have recurrent lung infections and a constant productive cough, the exorbitant cost of Kalydeco should probably rule out its use as a prophylactic. But for others, ?????.

 

[Aboveallislove]

Hey Stephen,
I do not know if Vertex provides anecdotal evidence to doctors as well; but it would be great if it did as that might convince more to do off label. Basically, the FDA prohibits and severely punishes pharama companies if they "market" drugs off label, but there is a reg that clarifies that they can give info to doctors if requested.

 

[jricci]

I just wanted to let you know that I didn’t find out any further information about how Vertex is defining residual function for this study. The research nurse at my clinic wasn’t able to provide an answer. I’m hoping that the inclusion criteria is broad and includes all Class IV and V mutations. I’ll be very upset if there are Class IV and V mutations that are excluded based on the in-vivo results. Based on these results, my mutation shouldn’t have responded but my response has been very positive. Vertex had no way of knowing my results or anyone who has been receiving it off-label because off-label usage has not been officially documented in a way that could impact how they designed the study. So frustrating…
I’ll call Vetex and CFF tomorrow and see if they have any more specifics regarding the inclusion criteria.

 

[triples15]

As I’ve previously mentioned, my CF doctor has prescribed Kalydeco for a number of patients who have Residual Function mutations. (I don’t know just how many.)

Some fortunate patients, myself included, got Kalydeco without any real problems from their insurance provider. For others, it took some effort on the part of my doctor and/or other CF center personnel to “convince” the insurance provider before the Kalydeco was approved. There were also cases where the Kalydeco was never approved. (Again, I don’t have numbers or percentages.)

All of the patients who got Kalydeco did show improvement, through not all to the same degree. The improvements applied pulmonary issues only. Improvements in digestive and sinus issues were very questionable.

If I recall correctly, my doctor is collaborating with another CF center to publish their experiences with Kalydeco and patients having Residual Function mutations.

I found the comment by Abovealislove very interesting where she stated that doctors can request information from Vertex regarding Kalydeco working on other mutations. On more than one occasion, I’ve contacted Vertex directly to let them know how well Kalydeco is working for me. I think I’ll call them again.

While I’m not trying to stir up a hornet’s nest, it’s hard to understand why some doctors are so reluctant to try getting Kalydeco for patients it could help. Yes, for patients who don’t have recurrent lung infections and a constant productive cough, the exorbitant cost of Kalydeco should probably rule out its use as a prophylactic. But for others, ?????.

Wow, how cool that your doc is trying to publish his patient's experiences with Kalydeco! That is awesome. This thread shows me that there are people (doctors and patients) out there REALLY trying to help get Kalydeco to us ASAP.

I think maybe we SHOULD stir up a hornets nest about docs who won't even try to get it for patient's that it's likely to help. LOL. I definitely have a constant productive cough, colonized pseudo, and staph accompanied by chronic pleural pain. I've found myself adding more and more to my treatment regiment over the years just to try to maintain baseline. I certainly don't *feel* like I'm in a good place wait (as my doc said). Anyway, now I'm beating a dead horse, so I'll sign off with that.

Thanks again,

Autumn

 

[triples15]

Hey Autumn,
I'm not sure if I mentioned this, if so, sorry, not trying to be a nag! But in preparation for your meeting with the doctor to request off label, I'd print off your insurance plans coverage for "experimental" or "off label." Most policies provide that it is covered if there is certain types of evidence and with your mutation there is. Also, under FDA regs, your doctor can request info directly from Vertex re any evidence it has that it works on your mutations.

No, you're most certainly not being a nag! I really appreciate that advice! I'll check on our insurance policy online. I think it's great advice because it's something I can rebut them with when they pull the flat "insurance won't pay for it" card.

Thanks a bunch for all your help, and for caring!!

Autumn

 

[triples15]

I just wanted to let you know that I didn’t find out any further information about how Vertex is defining residual function for this study. The research nurse at my clinic wasn’t able to provide an answer. I’m hoping that the inclusion criteria is broad and includes all Class IV and V mutations. I’ll be very upset if there are Class IV and V mutations that are excluded based on the in-vivo results. Based on these results, my mutation shouldn’t have responded but my response has been very positive. Vertex had no way of knowing my results or anyone who has been receiving it off-label because off-label usage has not been officially documented in a way that could impact how they designed the study. So frustrating…
I’ll call Vetex and CFF tomorrow and see if they have any more specifics regarding the inclusion criteria.

Darn! Too bad she didn't have an answer. I also hope the inclusion criteria is broad. Judging by the language in the description on clinicaltrials.gov, it's really hard to tell how they are going to determine residual function. There are no qualifiers for it like their were in the Denver trial. Anyway, repeating myself again. Do let us know if you get any answers tomorrow. Surely SOMEONE has one.

Thanks again!!!

Autumn