At the Roots: Natural Healing for Cystic Fibrosis
  • Blog
  • Cystic Fibrosis
    • Inflammation and Infection
    • Brochiectasis and Inflammation
    • The Microbiome: Your Gut and Immunity
    • Carbohydrates, Gut Flora, and Leaky Gut Syndrome
    • CF-Related Diabetes and Impaired Glucose Tolerance
  • Nutrition
    • Food Rules
    • How to Buy Food
    • What to Eat >
      • Carbohydrates >
        • Sugars
        • Grains and Starches
        • Fruits
      • Fats
      • Proteins
    • Healing Foods >
      • The Five Flavors
      • Medicinal Vegetables
      • Medicinal Fruits
    • Nutritional Supplements
    • Herbs for CF
    • Natural and Complementary Medicine
  • Resources
  • About/Contact
  • Consultation

The Orkambi Experiment

10/31/2015

28 Comments

 
PictureIvacaftor and lumacaftor molecular structures.
I mentioned in my previous post on my experiments with cystagon that I was going to try Orkambi, the drug designed to correct the CFTR channels in the cells of CF people with two deltaF508 mutations. Well, I did try it. And I'm not on it now. That should give you a hint of my general take on the whole experience. I'm back on cystagon and plan to stay on it indefinitely, or until Vertex comes up with a better drug for me to try. First, I'll give you a little summary of what it is and what it did for (or to) me, and then I will discuss the significance of its pharmacology.

What is Orkambi?
Orkambi is a drug made by the Vertex corporation, approved by the FDA in July 2015. It costs approximately $259,000 a year [jumps up and down in a fit of rage over the greed of the pharmaceutical industrial complex]. I will resist the temptation to rant about the prohibitive cost of this drug, as that's probably not what you're hear to read about. Moving on...

Orkambi is actually a combination drug made from two drugs: ivacaftor (i.e. Kalydeco, used for the  potentiation of the G551D mutation) and lumacaftor (a corrector). Even though it's been on the FDA fast track, it's been in trials for years. It is meant both to correct the faulty deltaF508 protein and potentiate it. What this means is essentially that it gets the CFTR protein to the right place in the membranes of our epithelial cells, and opens that protein to allow ions to flow across the membrane effectively. In theory, this would "fix" the problem of low extracellular electrolytes, which causes the sticky mucus issue that CF is known for. It is approved for use in CFers with two copies of the deltaF508 genetic mutation (homozygous). 

What it did for (or to) me
I gave Orkambi a month-long trial and then weaned off of it over 1.5 weeks. Overall, I did notice that by the end of the trial my lungs did feel a little bit clearer (not as clear as on cystagon), I had better energy and exercise tolerance, and my sinuses felt more moist. On the other hand, I had significant shortness of breath in the beginning that subsided after the first 4 days but never completely went away, I had a mild depression settle on me, my poops were irregular and too soft (they are usually perfect), and my blood sugar was completely out of control (peaks and crashes so extreme that I had to avoid carbs altogether). Towards the end, I also experienced a bad bout of pleural pain on my right side, and I am 90% sure it was a small pneumothorax (but there was nothing I could do about it anyway and it healed in less than a week). The other stupid thing was that I caught a cold for the first several days upon starting Orkambi, which made me pissed off that my experiment had been contaminated with compounding variables! I also lost a few pounds on Orkambi, mostly because it obliterated my appetite, which could have been related to the depression.

After I got off of Orkambi I noticed that I had postural orthostatic tachycardia syndrome (POTS) that lasted for a couple of weeks, and worst of all, on the 3rd night after I had stopped Orkambi completely (after the weaning period) I coughed up a very large amount of blood in the middle of the night, about 1/3 cup. Not ok. I immediately took a Yunnan Baiyao and continued to take it for the next 4 days. Luckily, I didn't have any more bleeding. I also noticed it took my finger pricks longer to clot than usual. The clotting time went back to normal after a few weeks off of Orkambi, as did the rest of the post-Orkambi symptoms. In addition, I had my triglycerides tested 2 weeks after I stopped Orkambi and they were sky high! Like 527 (normal is 35-150 mg/dL)! That was obviously alarming, so 2 weeks later I retested and it was back down within the normal range, at 129. The super high test result could have been an error (my sister hypothesized the lab tech was probably eating cheetos and forgot to wash his hands). If it wasn't an error, then my theory on this strange occurrence is that since Orkambi had caused my blood sugars to go crazy (and my A1c actually increased during that time too, up to 6.1) all that excess glucose had been turned into fat to store in my adipose tissue, causing my blood fat (triglycerides) to increase. 

After one month on Orkambi full dose I weaned off of it. I weaned off of it instead of stopping it cold turkey because of the increased risk of hemoptysis that has been reported after abruptly stopping Orkambi. This has something to do with its effects on liver metabolism of hormones, as I will discuss below. I did one week at a half dose (taking 1 pill twice a day instead of the normal dose of 2 pills twice a day), then for 4 days I took one pill once a day. For the last two days of this I restarted low dose cystagon because I was starting to feel mucusy and feverish again. I was planning on using a quarter dose of Orkambi for a week, but I was getting impatient and really wanted to be done with the side effects. It is clear to me now, in hindsight, that I did not wean off slowly enough to prevent the post-Orkambi bleeds that are so commonly reported. I probably should have done two weeks at the half dose and two weeks at the quarter dose, to be extra safe. 

In summary, I did notice that Orkambi cleared up some of the mucus in my lungs and gave me a bit more energy than usual. My quantitative lung functions did not improve at all during this time; in fact, they declined by a few points (probably due to shortness of breath). If I had stayed on it for a few more months I predict that it would have further reduced my mucus load and may have even improved my FEV1. However, I wanted to get off of it ASAP because I knew that, due to the nature of its pharmacology, many of the side effects would get worse with time, and I didn't want to dig myself a hole that I couldn't climb out of. Overall, the risks outweighed the benefits. Cystagon is a far superior drug, in my opinion, and I feel so lucky to have it so that I don't feel the desperation of having no option other than Orkambi. 

Pharmacology
This is a complicated subject and I've barely scratched the surface of the truth here, but from what I can gather from research and from my CF research-colleagues, here's what I know. Ivacaftor is a great drug. Simple (relatively), effective (for the G551D mutation), with a relatively uncomplicated metabolism pathway that causes relatively few side effects. Ivacaftor/Kalydeco has some pretty remarkable success stories attached to its use. This gave the next Vertex drug in the pipeline a ton of hype, especially since Orkambi is meant to treat people with the two copies of the deltaF508 mutation (homozygous deltaF508), which makes up about half of the CF population in the US.

​But Orkambi is anything but simple. Lumacaftor is a seriously complex drug with a complicated metabolism pathway, which actually interferes with the metabolism of its partner, ivacaftor. As a result, it has many side effects, some of them potentially dangerous. There have been no studies on the long-term use of Orkambi, since it was fast-tracked, but this drug is designed for long-term use (uh... like a lifetime). So we, as the first generation of users, are acting as guinea pigs. Now, some of us are quite desperate in the search for anything that can help. I totally get that. CF is scary and there are few solutions, especially if our lung functions are low enough. Orkambi has even worked, and worked well, for a handful of people in the trials (or so they reported). But Orkambi is not an ideal treatment, at least not in my opinion. And the next drug in Vertex's pipeline is a few years away and is also targeting the double deltaF508 mutation, with insider reports saying it is a way better drug than Orkambi is. Is it safer to wait it out and hope that the next drug is better? I know where I stand. But here's a little more info to help others make a more informed decision. 

The main issue with Lumacaftor is that it seriously messes with liver metabolism. The liver is where the majority of drug, hormone, toxin, and plant constituent metabolism takes place. The liver metabolizes drugs mainly through the use of cytochrome P450 enzymes, or the CYP450 system for short. There are many CYP450 enzymes, and certain drugs are metabolized by one or more of these enzymes. Of these enzymes, CYP3A4 is responsible for the majority of drug metabolism in the liver. Another twist to this situation is that drugs, toxins, or plant constituents (together called xenobiotics) can affect the rate at which specific enzymes act to metabolize other xenobiotics. For example, St. John's wort is a strong inducer of CYP3A4, which means that it increases the activity of CYP3A4, which would reduce the blood levels of a drug that is processed through 3A4 (because metabolism is increased, it is cleared through the system faster, reducing blood levels of the drug). On the other hand, some xenobiotics can act as inhibitors of a specific enzyme, which means that it reduces the activity of that enzyme and can cause elevated levels of a drug metabolized by that enzyme. For example, naringenin in grapefruit is a 3A4 inhibitor, so if someone is taking a drug metabolized through 3A4, drinking a lot of grapefruit juice can lead to high blood levels of the drug, which could potentially lead to an overdose. A xenobiotic that is metabolized by a specific enzyme is called a substrate of that enzyme.

The crazy thing about Orkambi is that it is both a substrate and a strong inducer of CYP3A4. Ivacaftor is a 3A4 substrate, and lumacaftor is a strong inducer. This means that in formulation, the dose of ivacaftor needs to compensate for its rapid metabolism induced by lumacaftor. But that's not all. Our sex hormones (estrogen, testosterone, and other cholesterol-based hormones like vitamin D) and some of our stress hormones (like cortisol) are metabolized through 3A4. Testosterone is also partially metabolized through CYP2D6, so its blood levels may be less disrupted by a strong 3A4 inducer compared to the blood levels of estrogen. Both males and females produce both estrogen and testosterone, in different proportions. By inducing 3A4, this can lead to significant imbalances in sex hormones and adrenal hormones that can have some pretty serious side effects, both during and immediately after Orkambi use. These side effects can include: vitamin D deficiency, disregulation of testosterone and estrogen levels, fatigue, increased risk of bleeding (especially hemoptysis), blood sugar disregulation, disregulation of blood lipids, postural orthostatic tachycardia syndrome (POTS), interactions with other drugs, and mood swings. The most common side effect is shortness of breath (as if we need more of this in our lives?) but I don't know if this is related to liver metabolism. 

The most frightening side effect seems to be an increased risk of hemoptysis or general bleeding in the first week or so after stopping Orkambi. We are trying to figure out why exactly this happens, but it is likely due to Orkambi's powerful effect on liver metabolism. It could be related to abnormalities in estrogen levels (estrogen induces coagulation) or it may be related more directly to the metabolism of proteins involved in the clotting cascade. Either way, it is a side effect that few doctors are aware of (since it happens after and not during Orkambi use), so if you experience this please make sure to report it to your doctor and your pharmacist. We MUST document all cases of when this happens so that the FDA becomes aware of this issue and investigates it further. 

​Conclusion
Overall, I was not impressed with Orkambi and would not recommend it to others. There are other options out there currently (like cystagon) and some better drugs coming down the pipeline for those with deltaF508 mutations. For people desperate for any kind of help, I think that cystagon may be safer to try first before Orkambi, but if you must try Orkambi, then start slowly and cautiously. It has been said that those with an FEV1 lower than 40% should start at a half dose, due to the shortness of breath that a full dose can induce. 

Orkambi is not the wonder drug that the media makes it out to be, so I advise CFers and parents of CFers to use caution when considering whether or not to try it.  
28 Comments
Lindsay
12/22/2015 01:31:39 am

My 12yo daughter started taking Orkambi two weeks ago, and since her very first dose her 2-hr post meal blood sugar levels have been much higher than normal. She is ''glucose intolerant'' and we spend two months every year checking her blood sugar to monitor the situation and in the past two years have not ever seen a spike in her numbers, but then just two days after starting Orkambi, her numbers jumped. Her doctors don't believe it's the Orkambi... they say there is absolutely no evidence that Orkambi would ever cause this to happen. I'm frustrated with them 'cause they just keep making me feel stupid and like I don't know my own daughter. I've scoured the internet to find any kind of proof/documentation that Orkambi is the cause... and you're post is the only thing I've found. Do you happen to have other evidence? Thanks.

Reply
Mica
12/24/2015 01:56:08 pm

Hey Lindsay. I am sorry your docs are in denial. There is such an institutional bias against patients/caregivers being empowered enough to know things about their own bodies. I have felt the same frustration often. The best thing that you could do is to join forums or facebook groups of other CFers and their caregivers who talk about these kinds of issues. You can ask there whether others have experienced the same thing that we have. Hormonally it makes sense, but many docs forget their pathophysiology early on in their careers. :( Plus there is a kind of Vertex-worshipping that is going on right now in the CF community that is blinding people to the side effects of this new drug.

Reply
Kim
3/24/2016 02:30:51 pm

Hi, found your post b/c my daughter started Orkambi and had to quit b/c of severe hypoglycemia. Sugars in the 30s 2-hours post meal. I have two null CYP2D6, so she has at least one, and one strong 3A4 she could have gotten. not sure if that would affect it though. She also has fatty liver disease alpha-1 antitrypsin deficiency. I'm fairly convinced the hypoglycemia is due to the liver. CF docs keep insisting "there is no evidence of that in the literature," but anyone with fatty liver was excluded from the drug trials, of course.

Reply
Mica
8/16/2016 03:27:41 pm

Hi Kim. So sorry to hear orkambi did that to her, and that is pretty strange. The only thing that I can think of off the top of my head is that the liver is responsible for storing a lot of glycogen, so if somehow abnormalities in the liver reduced her ability to store glycogen, when she gets low blood sugar there'd be not enough glycogen to help buffer the lows, leading to critical lows. I hope this has resolved since she's gotten off of it. If not, contact me and I'll look into it more deeply.

Reply
FN
4/3/2016 02:29:32 pm

Wow great explanation, thanks. I have had same issues and conclusions. Was on it for awhile and have been titrating off for last few months. Lately though my shortness of breath is bad and pfts have never been lower. Have been off Orki for about 10 days, hope it subsides.
I had significant SOB, low testosterone, weight loss, lower pfts, low vitamin S and my bone density tanked, good drug!

Thanks

Reply
Ed
5/24/2016 06:28:15 pm

May 24, 2016
Thank you Mica for writing about your findings on Orkambi. I am conserned for my daughter who is 18 years old and has Cystic Fibrosis. Presently she is on Orkambi and is in the hospital for lung issues and was going to have a procedure done to see what is going on. Her pft's came back at 94 and they decided at least for the time being to hold off on this. Needless to say they had found a blood clot in her Jugular. They had seen this during my daughters last visit to the hospital about two weeks ago and dismissed it as an anomaly. Now it has become concerning to them and we are looking at avenues to take to rectify this serious problem. My question to you Mica and to others is this possibly a result from her taking Orkambi as a dangerous side effect. She has been on this for over three months now. Thank you.

Reply
Mica
8/16/2016 03:35:58 pm

Hi Ed. So sorry it's taken me so long to reply (there was a problem with the website not alerting me to new comments). Yes, blood clots can certainly be side effects of Orkambi due to the effect that Orkambi has on estrogen. Estrogen encourages blood coagulation, and if orkambi has caused her estrogen levels to be abnormally high, this could lead to clotting. Furthermore, being hospitalized increases risk of clotting due to being sedentary, laying in bed more than usual. It is standard procedure at many hospitals now to give anticoagulants to CF patients during hospitalization to reduce this risk. Have they discussed putting her on anticoagulants? How did they treat the blood clot? Has orkambi helped her at all?

Reply
Simone
7/5/2016 02:33:34 pm

Hi, and thanks for the detailed explanation of Ivacaftor and Lumacaftor. I've been on Orkambi for three months now, and I've experienced almost nothing but fantastic results. Higher exercise tolerance, my non-existent appetite is now back and strong, and my lung feel less inflamed and healthier. HOWEVER, I have been plagued by weird arrythmias and tachycardia, as well as hot flashes and all of my heart tests have come back completely normal. Do you have any theories for why this may be happening? Thank you so much.

Reply
Mica
8/16/2016 03:44:55 pm

Hi Simone. Very glad that it's working for you! Orkambi did a similar thing to me, especially when laying down or getting up from laying down. This is usually called POTS (postural orthostatic tachycardia syndrome) and may have to do with the processing of aldosterone (which controls blood pressure) via the CYP450 enzymes, but we don't really know. Do you also have low blood pressure? Increasing fluid intake and electrolytes may help.

Reply
Jonathan Colvin
8/9/2016 01:50:21 am

I've had the opposite experience with orkambi and blood sugars. My cfrd seems to have gone away and now I don't need insulin anymore. I went low a few times after starting orkambi before I figured out that I just disn't need the insulin at all.

Reply
Angie
9/17/2016 07:05:48 am

Orkambi has been fabulous for me, my lung function has gone up 20%, my cough has vanished, I've stopped some oral antibiotics and antifungals I was on for years due to no longer culturing those organisms, my reflux is gone, and I sleep through the night. HOWEVER, I do have a plethora of side effects: high blood pressure, high testosterone (I'm female), breathlessness (no chest tightness), and tinnitus. I'm torn about whether to continue or stop. Is it easy to get cystagon?

Reply
Christian Reinhard
12/25/2016 04:33:31 pm

Does anybody feel that Orkambi SOB correlates with antibiotics? I have been taking Orkambi for almost 6 months now and it is doing good work. Mucus is thinner and GI tract seems more stable.Normally no SOB, expect the first few days. I have the feeling whenever I start taking antibiotics, oral or inhaled I get SOB.Anitbiotics of all classes I used to take for 2 weeks without any major side effects I now have to stop after 5 days because I get trouble breathing and my O2 stats go down to 91/92%, where I am usually around 94/95. Anybody else experiencing this

Reply
Ben
1/5/2017 01:44:19 am

So I have been on orkanbi for one year. My pfts went down after I started about 7%. Which was totally connected to the medication because I felt pretty good honestly. So I have been more sick this year. Seem to constantly have an upper respiratory tract infection that no doctors care about to treat. They just told me they couldnt prove the medication wasnt working. Basically my pfts would have to drop consistently. I totally feel the short of breath every one talks about. My doctor tells me I dont know what I am talking about and that particular symptom only lasts a year. I am fed up with the BS. They seem to just constantly tell me I dont know what I am talking about and I dont know what I am feeling. I am pretty mad they didnt explain the negitives as well as they should have. I think they just wanted to test the drug on me.

Reply
Mica
1/9/2017 12:24:44 pm

I am so sorry to hear this Ben. It is endlessly frustrating to me when docs don't do their most basic job of listening to patients. I will say that it may not be entirely their fault that they didn't warn you of potential negative side effects - they may not have known about them, since this is such a new drug, and Vertex may not have wanted to educate them about the side effects. The fault lays partially in the FDA approval process where negative data is not not always included. It is part of our job as patients to help educate our doctors, however unfortunate that may be. I wish you the best.

Reply
Fareena Fansia link
3/5/2017 11:03:41 am

Hi . My son 24 has lung function 20% started Orkambi with half dose of two tablets . He started in August 2016 and he got frequent chest infections was also hospitalized. It makes him cough a lot including shortness of breath . Although he gets infections almost every month or two but after this med he gets more of coughing . It gave him severe headaches in the beginning but it subsidized. He feels more panic attacks too . We stopped after 3 months . He gained weight with it the only positive point . We have restarted in feb the doctor wanted to give him full dose but he didn't agree and now again he has infection and is on intravenous. We don't understand whether he is not taking full dose that increase mucus but can't take it out or whether this med is not suitable for him . The doctor insists on giving him full dose which my son doesn't agree .Anyone has faced this situation please let me know

James
3/23/2017 12:13:47 pm

I've been on Orkambi since the phase one trials. I've had strong results and no side effects. You say you wouldn't recommend it (and while your personal anecdotes while taking the drug may be true), reading the rest of your blog that's hardly a surprise. Your Dunning-Kruger quotient is off the charts.

Reply
Sonja41CF
4/1/2017 06:24:13 pm

James, I'm ecstatic that Orkambi has worked so well for you, but in Micca's defense... she's right about the fact that no one hardly ever informs us of the negative side effects, even the pamphlet doesn't include ALL of the possible side effects. Which by the way... I'd rather hear from someone's own personal experience rather than from a pharmacologist who only knows the scientific side of things. I actually appreciate the honesty and openness from reading and hearing from other people's' personal stories! Keep posting them! Thank you!!!

Reply
Mica
3/23/2017 04:24:05 pm

I'm very glad to hear you've had good results! While your comment is a bit insulting (as is the temptation with internet commenting), I am happy for you. There are certainly many that fall into this category, but also many that don't benefit, or that have negative side effects. I sure did hope I was going to be one of the ones to benefit! A miracle drug would have been nice, to say the least. But alas, it did not turn out so well. My point in writing this was that at the time, everyone in the CF community was gung-ho on it but no one had yet written about the negative reactions lots of people were having, and why. I believe we need to exercise caution, especially when fast-tracked blockbuster drugs hit the market. Anyway, I hope it continues to work for you! Take care.

Reply
Dawn
3/29/2017 12:11:48 pm

My 18 year old son is his healthiest ever since starting Orkambi in September. Lung functions are highest in the last five years and gained 12 lbs (finally over the 50th percentile in weight). Liver enzymes have stayed consistent and no blood sugar issues. We have never been happier. Hopefully there are others having as good as an experience as ours.

Reply
Sonja41CF
4/1/2017 06:17:44 pm

O.M.G. I can't believe I just read this! My Dr. insisted that I keep taking Orkambi even though I reported feeling like a "fish out of water!" So he told me to take Advair or Symbicort - which I felt contributed to a spontaneous pneumothorax! Since I stopped taking an inhaled steroid... I have not had another lung collapse since! I swear... sometimes I think my Dr's are trying to kill me by adding more medication on top of medication that are only worsening my situation. I'm already extremely upset that I have had 5 embolizations that didn't work and no am being considered for a lobectomy! I thought I had the best care team possible, but I have learned that they're not even on the list for being the top CF centers. Contemplating on finding another Dr. Even if that means moving cuz they never tell me things like this, or the truth. Period. Thanks again for this info.

Reply
Daniel
4/20/2017 03:26:54 am

Oh. I have some comments. And some will not like it. First, i am a now retired medical professional who has worked in a hospital system for over eight years. I work with facts when it comes to treating illnesses. While indeed there have been limited studies that show 'natural' products helping with cf, it still is limited, very much so, and many studies are not double blind. You can use natural products if you want but make no mistake, taking your prescription meds as directed by your doctor is a must. How do i know that? I have cf myself and had to retire due to it. I am 42 with a fev1 of now 56%. It was 34%, before i started Orkambi. Now let me say this, yes, some do benefit more then others. This is the very first drug of its kind. And like any first there will be improved versions going forward. But lets not kid ourselves, it will be drugs of this similar mold, be it by vertex or others, that will end up changing the face of cf. And as a active clinical trial participant, from what the doctors at johns hopkins hospital and others tell me, it will be sooner then later. I have no issue with people wanting to ADD eastern medicine or natural health ideas to their care, but to only use those or to mostly just use those against docs wishes is just dumb. I sure hope no one here would advocate or promote such a thing. Now with regards to what some have said above: first you cant do a successful trail of Orkambi over such a small time period. The first two months for me caused more coughing and feeling not the greatest but my doctor, as well as the clinical trial ones i worked with, told me this would happen until my body adjusted. I mean, it's actually changing our cells you gotta expect some adjustment time. In addition, it does NOT cause lower testosterone levels or bone density problems! That is cf folks. As adults get older we are going to have bone density issues due to the lack of ADEK and calcium absorption. And yes cf effects testosterone levels too. Cf plugs up many organs and glands, including our male bits. I started taking androgel 4 years ago due to cf. Also Orkambi can increase liver enzymes in about 20% of folks. It did not for me. But it also doesnt for everyone who takes it. As a result of this drug i have gained weight, improved lung function and increased FEV1. I now can go to the gym for the first time in years. What i am saying is you must not take a few peoples opinions and experiences, including mine, and jump to conclusions. You gotta go with the data we have now. And that shows that it helps many more then it does not. Again if you want to add other things to your prescription protocol go ahead. I do. But i will never advise anyone to stop taking what your cf doc asks you to. I have seen some cf friends do that thinking thst they know their body better then docs (which may be but you dont know cf better), knew others that actually ONLY took 'natural ' items to treat their cf. And well, i dont really associate with them anymore. Not that i dont want to. Its just that they are dead now. But again, i am 100% sure no one here would condone such behavior, so that is a relief. So....take all meds as prescribed, add natural or eastern concepts, but never substitute, dont drink or smoke, eat well, exercise, and meditate. But make no mistake, while we need to keep these for profit companies honest, it will be research by them and most likely sponsored by the CFF that will lead to even more refined versions of these drugs that will save lives.

Reply
Mica
4/20/2017 08:09:15 pm

Hi there Daniel. Thanks for sharing your experiences. You are indeed lucky to have such unusually good results! I am very happy to hear it. I have discussed the topic of orkambi and other ivacaftor combination drugs with some of the top minds in the field of CF research for a few years now, and so my opinion is not only informed by my own experiences but by in depth discussions with researchers, pre-market trial participants like yourself, and many post-market takers of the drug (including at least a dozen that have had to get off of it due to the side effects it has induced). Some of your claims are not backed up by evidence, and I think you may not have considered quite fully enough the implications that severe induction of CYP3A4 enzymes have on steroidal hormones in the body, including testosterone, estrogen, and stress hormones. Please read more about this if you can.

One specific point I would like to make is that there were many participants in the phase 2 and 3 trials that had to drop out due to their inability to tolerate the side effects of Orkambi. Most people don't know that when a participant drops out of a trial before it ends, their experiences are not included in the final analysis of results, thus artificially skewing the end result of trials to seem more positive than they actually are. This is a significant point to consider when making generalizations about the efficacy of Orkambi based on recorded trial data.

It seems that you are unaware that the effect that CFTR mutations have on infertility in males has nothing to do with mucus plugging of gland ducts; it is actually caused by congenital absence of the vas deferens (CAVD) that happens before birth in males, due to the CFTR mutation itself. There is some effect on sperm production and activity in post-pubertal males, but this is secondary to the CAVD. Thought you'd like to know that.

Another point I'd like to make is that not all CF specialists are very well-informed about CF, and some highly-educated CF patients know much more than their doctors do. Some doctors take it upon themselves to stay educated and up to date on the latest research, but most do not. Not all of my doctors know as much about CF as I do, in that I've done more research than them (trust me, I've tested them). It's a sad fact, but it's true. Putting blind faith in your doctors is a recipe for failure. I have talked with dozens of CFers whose doctors have make very poor decisions based on biased or incomplete information and have done significant harm to their patients. That said, some doctors are very, very smart and very well-informed and make very good decisions. But not all. We should never assume that doctors know everything there is to know about CF. They must prove it to us. In many parts of the country where there are remote CF "specialty" centers, doctors are poorly educated and have very little access to the innovations coming out of research hospitals. There are only a handful of really high-quality CF centers in the US, and Johns Hopkins happens to be one of them (I went there when I was a kid and I was impressed by their clinic... their hospital care sucked though). Often times when CFers get very sick in their end stages, they have to move or transfer to better CF centers, if they have the means to do so (many do not). So it is unwise to consider all CF specialists to be equal. Plus, even the smartest CF specialist in the world doesn't know everything, and is limited by her own biases, as all of us are.

It is clear that you have a high standard when it comes to evidence-based medical decision making, which I approve of, and so I ask that you hold yourself to that same high standard. If you make a medical claim, as you do in your comments, please back them up with evidence. Thanks.

Reply
Buzzy
1/13/2018 07:57:56 am

Hi Mica,
thanks for the blog and all the discussions on here. I am generally reading and absorbing the information the various contributors present rather than participating in the discussion as my son is not taking Orkambi. However, as a clinical scientist I would like to correct a misrepresentation in your reply above:
"One specific point I would like to make is that there were many participants in the phase 2 and 3 trials that had to drop out due to their inability to tolerate the side effects of Orkambi. Most people don't know that when a participant drops out of a trial before it ends, their experiences are not included in the final analysis of results, thus artificially skewing the end result of trials to seem more positive than they actually are. This is a significant point to consider when making generalizations about the efficacy of Orkambi based on recorded trial data."
As you may or may not know, clinical research is one of the tightest regulated areas of work world-wide and the way missing data affects results is one of the topics that is considered important enough to warrant a lot of guidance and regulations: Firstly, ALL data collected has to be included in the so-called Intent-to-Treat analysis to show efficacy (and this is the analysis reported to the world at large as well as the regulators in phase III). How data from patients not completing the trial is used here, has to be outlined in the statistical analysis plan which is finalised before the study is unblinded. There are different scientific methods and depending on the disease area the most apppropriate one is used, e.g. the "last observation carried forward" which is the most commonly used. Hence, if a patient discontunies the trial after 4 weeks because of an Adverse Event then his/her last efficacy data point is carried forward to the end of the study and included in the (for arguments sake) 6-month efficacy analysis. The method deemed to produce the least bias FOR the study drug has to be selected. If the Adverse Event had an impact on the efficacy parameter (very likely in Orkambi studies) then this has the potential effect of making efficacy less rather than more. Hence, the approach is conservative. In terms of safety, ALL collected data from the moment the patient signs informed consent is included in the analysis and fully reported in the Clinical Study Report for ALL patients. NOTHING is ever excluded.
It is very unfair to say otherwise. The studies are run to demonstrate the efficacy and safety of new chemical entities and the guidelines for this have developped over the last decades and any attempt at fiddling with the data or hiding data or whatever has a very large chance of being detected with horrific consequences for anyone involved. The most likely party to play foul btw are the study sites themselves, as to them a study is a possibility to earn money and sometimes that makes people greedy. However, the incidence of that has also been much reduced to the many measures in place to ensure fraud cannot happen.

Sonja41CF
4/24/2017 04:34:45 pm

Daniel, I'm super happy that Orkambi has worked so well for you! While it did seem promising in the beginning (for me), after several months of taking 1/2 a dose - my lung functions continued to deteriorate quickly! I couldn't breathe - at all. It was also effecting my liver functions dramatically. And you're probably right about Advair & Symbicort not causing my lung to collapse, but I just made that association because the Advair being a power substance and the side effects being increased lung infections, etc. And like I mentioned, since I stopped taking both drugs, I have seemed to stabilize a little bit more. Each person is affected differently, but like I also mentioned... I'm just grateful to hear both the good AND the bad since the Dr.'s don't always know or are forthcoming with vital info. But I'm really glad that it's working for you. Perhaps like you said... some adjustments to the medication will improve sooner rather than later. Hopes are high! Thanks for your input.

Reply
Ben
10/25/2017 04:06:47 pm

Daniel gave a great comment about and it feels from an outsider that Mica is overwhelming butter that Orkambi did ot work for her (which is totally undstandable) but many drugs are not suited for everyone. Several fungal drugs some patients cannot tolerate but that doesn't make them detestible drugs. Your blog post was good...1 month on Orkambi is not enough to do a fair assessment. Being i
so irritated by a reader who doesn't side with you is purile. Shame Mica

Reply
Craig Hopp
4/9/2018 04:22:43 pm

Hello, Today I have started my first dose of Orkambi, my PFt's were measured today also FEV1 29%. It has been 5 hours since the initial dose and I have shortness of breath above normal. I am hoping it is just temperary! I will keep a running comment as things progress, I have high expectations due to the media out there, however we will see what really happens in reality! Cheers to all.

Reply
Craig Hopp
4/10/2018 11:44:05 am

For me the Orkambi experience was short lived, I unfortunately had an allergic reaction to the drug, severe shortness of breath, which after reading other people's experiences was expected, however as the day went on my skin turned very red similar to a severe sun burn and was radiating heat, also a tingle sensation in the tongue. I am not sure as to which drug caused the reaction but I am hoping it was lumicafter. If it is ivacafter then that takes away the next generation of kalydco that is coming tezacafter which leaves me screwed!! Anyway good luck to everyone. Cheers!

Reply
Craig Hopp
4/11/2018 07:40:49 pm

So now I have a question I am hoping someone can offer some insight on the chemistry, Orkambi (lumicaftor/ivacafter) was unsuccessful due to an allergic reaction, So I am looking at trying Symdeko (tezacafter/ivacafter) assuming my allergy was with lumicaftor and not ivacafter? Anyone else have experience in this? And was the switch a success?




Leave a Reply.

    Author

    Mica is a clinical herbalist specializing in cystic fibrosis, severe respiratory diseases, nutrition and digestion, diabetes and blood sugar disregulation, and immune disregulation. Through their own personal experiences with chronic illness, they are passionate about empowering people to take charge of their own health with natural, holistic, and integrative approaches. Please ask questions or share what's worked for you! 

    *****************************
    Disclaimer: The content of this website and blog is for educational purposes only and should not be considered medical advice. I am not a licensed medical professional and do not take responsibility for any actions taken by the reader as a result of access to this information. 
    ​*****************************

    Follow me on Facebook:
    ***********************
    Donate to keep 
    this work going:


    Categories

    All
    Chinese Medicine
    Cold And Flu
    Diabetes/Blood Sugar
    Digestion
    Essential Oils
    Experimental Drugs
    Food And Nutrition
    Food Combining
    Gaps Diet
    Gluten
    Gut Dysbiosis
    Hemoptysis
    Herbs
    Lifestyle/ Quality Of Life
    Lung Disease
    Natural Medicine
    Our Microbiomes
    Presentations
    Recipes
    Sinuses
    Specific Carbohydrate Diet
    Stomach Acid/ GERD

    Archives

    December 2020
    September 2020
    March 2020
    December 2019
    July 2019
    March 2019
    February 2019
    December 2018
    October 2018
    May 2018
    January 2018
    May 2017
    April 2017
    November 2016
    October 2016
    July 2016
    June 2016
    April 2016
    March 2016
    February 2016
    January 2016
    October 2015
    August 2015
    April 2015
    February 2015
    December 2014
    September 2014
    August 2014
    July 2014
    June 2014
    April 2014
    March 2014
    February 2014
    January 2014
    December 2013
    November 2013
    October 2013
    September 2013
    August 2013
    July 2013
    June 2013
    May 2013
    April 2013

    RSS Feed

Powered by Create your own unique website with customizable templates.