Before Trikafta, I usually had a 5+ day stay in the hospital every year, and sometimes I have would very stubborn respiratory infections that just wouldn't go away. I was mentally preparing myself for inevitable decline and eventual death.
Trikafta changed my situation dramatically. I've had no hospitalizations, and most the classic CF symptoms are either gone or extremely diminished. It can't undo a life of damage to things like my pancreas, vas deferens, etc, and I still take medicine to digest my food, but overall, it's as close to "normal" as I could hope for at this point.
The only real downside: weight gain. With CF the pancreas is blocked, so you lack in digestive enzymes, and it's a struggle to maintain a healthy enough weight to battle respiratory infections. After Trikafta, I gained some 30 pounds, and have a big belly on my small frame, and went up some 6 inches in the waist. To add insult to injury, it happened during the spring and summer of 2020, when buying clothes was a challenge due to the pandemic.
Speaking of the pandemic, the timing of Trikafta was amazing: it kept the normally full "CF floors" of hospitals empty, opening up those beds for those with COVID and keeping CF patients less exposed.
One side effect I should mention: many report extreme anxiety. However, I was starting an anxiety medication for the first time (something I should have done 20 years ago, but alas ...) and so those effects were muted or hidden to me.
It's utterly amazing to hear of another group of sufferers who are the beneficiaries of modern miracle medicine.
Personally, I suffered from an extreme case of eczema my whole life, which left me effectively a disabled person. Although eczema doesn't have a significant effect on life-expectancy, there wasn't all that much to live for, and I had basically given up on being able to do normal things like exercise or travel.
So it was very surprising to "hear the good news" that Dupixent(https://en.wikipedia.org/wiki/Dupilumab) was being released in 2017 (also fast tracked as a breakthrough therapy), I got on it, and it's made me 98% a normal person.
Here's to continued funding for new miracle medicines to help more groups of sufferers.
I know someone with relatively bad eczema and I believe you when you say you believed you had nothing to live for. I’m genuinely glad you were relieved of that. It seems like it can be terrible to live with.
Yes, the worst was a period of months when I was effectively a burn victim (>70% of body with severe bleeding sores, and fully bedridden). The worst part was that, unlike with a burn victim, it wasn't clear to me if I would ever heal out of it.
Luckily it got a bit better to at least get out of bed, and then Dupixent came along a few years later.
Oh god. That’s virtually incomprehensible to me. I woke up feeling a little down today, but I’m realizing I should be a lot more grateful for my healthy past and present. A little cold doesn’t matter in the scheme of things.
It's really amazing how much the human mind adapts both upwards and downwards. These days I find myself sad about the same kinds of stuff as everyone around me (money, relationships, etc.), and I honestly don't think about where I was just ~6 years ago.
But in really down times, I do find it a mental panacea to just remind myself about my past which pretty much instantly solves any feelings of depression.
I suffer from allergies/hay fever for 3-4 months of the year. When I was a teen I used to take cetrizine which would sort of help, but it left me feeling groggy and tired a lot, which was in some cases worse than the allergies.
Fexofenadine became available OTC available in the UK in 2020 and the pharmacist suggested I try it. I don't even carry tissues anymore during the summer months. If I ever miss a day though, it's immediately obvious.
It's not life or death, or anything like it, but it's a wild improvement in my qualify of life.
You might also want to consider immunotherapy - it’s quite effective for most and can offer long term desensitisation. Available both privately and via NHS (for severe pollen allergies) in the UK.
Immunotherapy is not a silver bullet, and it can take years before any positive improvement is noticed. There's a not insignificant time sink involved with going to the doctor twice a week. And the immunity doesn't last forever.
Yeah my symptoms aren't anywhere near bad enough to warrant even a monthly trip to the doctor. I was miserable for 3 months of the year either sleepy or sneezing and scratching, now I have a daily pill for £10/month for the summer.
You don’t need to see a doctor regularly with sublingual immunotherapy. It’s just a couple of drops or a tablet once a day for 5 mins. No side effects (it’s effectively microdosing the allergen to desensitise the body)
I'm in the UK, doesn't appear to be an NHS treatment. Given the choice between $150/month for a tablet once a day (immunotherapy) or free for a tablet once a day (fexofenadine - my pharmacist can write a prescription for it and I live in Scotland where prescriptions are free), I'll take free thanks!
For the value that Dupixent provides for me (effectively infinite), I'd do just about anything. So the injections don't bother me at all.
Though injections do make international travel a bit more complicated. Daily-pill eczema treatments would definitely be more convenient in that respect!
I was actually on Dupixent for a while and I was one of the non-responders, so my derm put me on a JAK inhibitor daily pill.
The convenience is offset by higher risk of side effects, though luckily I seem to have avoided those.
The pills really seem to be the solution for me.
My eczema had gotten pretty bad in recent years, and much of what you said resonates with me, though I don't think I ever got to the point of being effectively disabled.
My skin is like 90% smooth now with some last stubborn patches, but I'm hoping with time they and the residual scarring will start to disappear.
Sorry to hear you're a non-responder to Dupixent. But really glad you found a different pill that seems to work!
I use to worry that my body would someday stop responding to Dupixent, and my whole life would suddenly crash down around me. But luckily that hasn't happened yet, and with all the monoclonal antibodies in the pipelines, I'm actually confident medicine will be able to outpace my condition.
My 8yr old daughter has been on Kalydeco (one of the active compounds in Trikafta) since it was approved and it means she'll live a fairly similar life to her twin sister, health wise. We only have to do airway clearance treatment when she's sick. It's crazy for me to think what a different life shed have had even being born a decade before.
My brother 12 years ago could have been you, as I read your comment. A double lung transplant and myriad complications later, and he passed on from this world.
Reading your experience makes me so happy that people with CF are finally seeing a light of hope in their experiences. You do all the walks, donate the money, remind people this disease exists and it’s so destructive but it always kind of felt like science wasn’t throwing a lot of energy into CF, so I’m so glad to see this development. I’m so happy for you. I wish my brother could have had that chance, but I imagine, given his incredibly generous nature, he’d be just as happy for all the CF survivors today who now have a fighting chance.
The CFF has actually done a good job of taking the lead. They approach it in a very startup-like manner. Trikafta is one of the results of that effort.
I don't have CF, but I am inspired by the pace of scientific advancement when I hear stories like this one. Thank you for sharing, and I hope every one of your years brings further boosts to your health.
I don’t know very much about CF so I took the opportunity to read a little about it.
A hunch struck me that CF seemed like a disease where N-acetylcysteine might be useful (NAC). Have had good and unexpected results with NAC in relation to Type 1 diabetes; not widely used in that context afaik but recent literature describes mechanisms and benefits.
NAC is quite strange. Does a lot of things and works for a lot of stuff. Enough to seem a bit implausibly effective. It’s a mucolytic antioxidant which also replenishes certain important biological precursors and also has an effect on histamine and mast cells somehow, not just through being mucolytic (“slime-dissolving”). And more iirc. Just… does a lot.
There’s literature on positive effects in congestion, anxiety, diabetes, placental health, brain damage from methamphetamine poisoning in rats (!), COVID illness and recovery, and on and on. As I said it seems kinda implausible how widely NAC seems to help. I’ve seen it have very clear and obvious benefits. T1 diabetes isn’t really something you can delude yourself about; no bargaining with it.
As I read about CF I thought of NAC. I didn’t seem mention of it on the Wikipedia page for CF, but a Google Scholar search turned up some recent papers.
‘N-acetylcysteine (NAC) and Its Role in Clinical Practice Management of Cystic Fibrosis (CF): A Review’
—Guerini & co. ‘22
https://www.mdpi.com/1424-8247/15/2/217
Wanted to share and ask if you had any experience with or thoughts on NAC?
It's been an alternative remedy in the CF community for a while. People with CF hoard glutathione within the cell and have too little on the surface, so some people with CF use inhaled NAC to address the lack of surface glutathione in the lungs.
In Sweden we treat with NAC and bisolvon, amongst others, so it is not alternative. We have the highest life expectancy for CF in the world. But remember, correlation is not always causation.
Thank you for sharing this with us, I'm so glad for you! I can hardly express how amazing this development is to me! I had not heard about it before today.
I have 2 boys with CF, 12 and 14. They got ivacaftor from 4 and 5 yrs old, respectively. Pancreatic function returned for both, but has decreased over the last few years, FYI. just a data point. Don't stop the daily treatments either. It's not a full cure. The boy with a 32 mmol sweat is healthier than the boy with a 44 mmol reading.
CF has no bearing on what I can tolerate, though the fattier the food, the more difficult it is to digest. In a situation where I had no access to my medication, I'd focus on eating simple carbs, like fruit.
ok, now you got me wondering... could a pregnant mother take this drug if they're at high risk of their fetus having CF (or confirmed via pre-testing) to prevent this?
(Or possibly will continue taking it if they have CF as we can expect more CF patients to have children)
It's a homozygous recessive disorder. If two carriers reproduce, there is a 25 percent chance the child has CF. If a woman with CF has children with a carrier, there is a 50 percent chance the child has CF and a 50 percent chance the child is a carrier.
Ninety-five percent of men with CF lack a vas deferens, leaving them effectively sterile. The medical community is understandably reluctant to assist two people with CF in reproducing together as their child is guaranteed to have CF.
If you are at risk of having a child with CF and know it, a best practice is to try to not conceive a child with CF.
I doubt taking a drug during pregnancy would prevent a male child from being born without a vas deferens and see no reason to care. Just try to not have a baby with CF. It's called a Dread Disease for a reason.
It won't alter the underlying genetic condition, but there has been at least one case report that taking these CFTR modulators during pregnancy can improve the condition of the fetus/newborn:
Both of these babies are female. I am not at all surprised that the drug helped in the way described in the articles, but it doesn't actually indicate whether or not it could impact the vas deferens since that's a defect in the male reproductive tract.
According to the CF Foundation, the cause of the lack of the vas deferens is not conclusively known.
My wife has several family members with CF. They have started on trifekta and it has changed their lives radically to the point the disease barely effects them day to day.
It truly is a miracle and a breakthrough, and the only shame is that these brave pioneers are only getting $3 million for their heroic efforts.
Meanwhile the actual cost of the medicine is $10k a dose.
Nobody actually pays those sky-high drug prices themselves. It’s a scheme to extract as much money as possible from insurers.
Companies often have programs that provide the drug free of charge (or at a nominal price) to people without insurance. They might also have “copay assistance” programs where they reimburse patients for their copay to bring the out of pocket costs down.
The goal is to maximize the amount billed to insurance companies. They’ll go out of their way to reduce the amount billed to the patient directly, because that results in more patients signing up and enabling them to bill more insurance companies.
It’s not a good system, but it’s how things work right now. Nobody pays that $100-300K price themselves. Well, we all do through higher insurance costs.
while employed Premiums = $0. while unemployed, premiums = $3600/year for $0 deductibles for private insurance. would you rather pay 10% of your income in higher taxes like so-called universal healthcare providing countries maintain?
This is such a short-sighted take. Who do you think pays for your $0/year premiums? You do, through reduced wages.
The main difference between US healthcare and socialized health care is that in the US, nobody is responsible for lowering healthcare costs... and so they go up. Why do you think PE loves buying up healthcare facilities?
Yes, personally. Instead of my employer paying for my healthcare (and that being factored into base salary), I would rather receive that money as salary and pay higher taxes. The idea of employers paying for health insurance in the US only came about in the first half of the last century as a way for companies to attract employees without having to raise/compete on salary.
I have the best insurance policy my employer offers, where I have a $250 annual out of pocket max. I pay an additional $230/mo for the coverage over their base plan; I pay $900/mo to add my wife to the plan.
I'm just one datapoint, and there may be better plans out there, but you're presenting an alternative that doesn't exist for 95% of Americans.
Can you give me a link or reference to this incredible $3600/year for $0 deductables insurance?
That's cheaper than I pay with my employer covering most of my healthcare. That could be literally lifesaving for friends of mine who currently have to choose between paying about $800/month for insurance with deductables or going without.
One look at the individual market for insurance shows that you will be paying many times the quoted figure if you want insurance that you can actually use, and you will have $8k deductibles and higher out-of-pocket maximums with cheaper insurance.
> It’s a scheme to extract as much money as possible from insurers. [...] The goal is to maximize the amount billed to insurance companies.
A big part of the goal is being able to bill a profit, insurers generally require significant drug rebates for coverage. So you triple the sticker price of the drug, offer a 66% drug rebate which the insurer can advertise to their client under the guise of fighting for their access, and they cover your drug at essentially the price you wanted for it in the first place (modulo nonsense like prior authorization, and insurance kickbacks).
I personally consider copay assistance to be essentially fraudulent as a concept. The drug company is literally paying the patient to invoke an insurance benefit that kicks a bunch of money to the drug company.
I imagine that when an auto body shop pays their customers’ deductibles, it is fraud, legally and ethically.
Not having to deal with insurance & copay shenanigans for my daughter's CF meds is one of the things that keeps me at the large tech company I work at...
> 2014: The CF Foundation sells royalty rights for CF treatments developed by Vertex for $3.3 billion – bringing resources to the fight against CF never thought possible
The drugs may have never been developed without the CFF. They arguably took more financial risk than vertex. Vertex was trying to be a hepatitis c company at the time and cf was an off focus program that happened to come with an acquisition. With out CFF funding my guess is the program would have been cut. The fact that the nonprofit got a royalty stream from their significant financial investments is good practice.
The drugs are expensive, but how much is a patients life with? How much money does stopping progression save the healthcare system financially? Aside from giving the patients more normal and longer life, persistent and repeated hospitalizations and lung tra transplants are very costly and poorly effective.
This is an example of transformative Medicne. Our society needs should prioritize such work.
> high licensing costs that they paid to .... drumroll.... The CF "Foundation"
What are you talking about? The CFF invested in the research being done at Vertex and then sold their shares in the investment. There are no licensing fees.
> made the drug unavailable to most patients
Where’s the data showing the majority of CF patients aren’t receiving Kalydeco or Trifekta?
> CFF invested in the research being done at Vertex and then sold their shares in the investment
Maybe they should just rebrand to CF Investment Fund then. I thought it's a charity with a mission of improving the lives of CF patients not an investment vehicle that happens to invest into compounds around CF. I hope the patients who contributed to the charity and now can't afford the drug are happy with the rate of returns
I have a friend who has been saved by this and I have two funny points.
CF makes you not process food correctly so you can eat a ton of food and not gain weight. After taking this medicine he was upset because his body started processing food correctly and he put on a bunch of weight initially.
This really is a life saving cure for most general genetic versions of CF but he also remarked that it’s great they found a cure now because it’s basically a white people disease and the amount of funding it got for a cure was likely going to come under scrutiny.
Re."white people disease," I thought this was a neat excerpt from later in the article (about Parkinson's, to be fair, not CF):
> Njideka Okubadejo, a neurologist at the University of Lagos in Nigeria, welcomes the award announcement. Okubadejo, Singleton — who leads the Global Parkinson’s Genetics Program — and others have identified a new genetic risk factor for Parkinson’s disease in the GBA1 gene in people with African ancestry that is rarely seen in those of European descent7. “The next step is to find a biological mechanism by which the gene causes the disease,” Okubadejo says. “Then you can build upon that to reduce the likelihood of the disease occurring.”
The distribution of random genes among ethnic subgroups is always an interesting glimpse into the situational tradeoffs that certain genes bring. Like how the gene that causes sickle cell anemia is really good for malaria resistance... but it also gives you sickle cell anemia. Which might actually be a decent tradeoff when malaria is a constant threat, so you can imagine why it's prevalent in areas where malaria-carrying mosquitos flourish.
Or you hear about different HLA subtypes where like, one variation offers some kind of useful trait or immunity, but it also brings an increased risk of skin cancer, but the people who carry that gene generally lived in an area without much sun and so it was still a net advantage. Until modern times, when those people have descendants across the globe...
Also, very glad to hear your friend's doing well :)
Another interesting link is that between mental health issues (schizophrenia, bipolar) and "elite" creativity and the risk of losing the latter if we can ever gene edit the former out of our genome.
Siddhartha Mukherjee talks about this in The Gene.
Fortunately, it seems that there is a huge set of genes that affect intelligence, which hopefully makes it impossible for the forseeable future to develop a gene-therapy for them. Diseases like cystic fibrosis are low-hanging fruits compared to that.
White and mostly male. My local university or more precisely certain students wanted to drop CF as a cause to support due to those factors. Pretty disgusting and it was quickly dismissed for what it was. The uni still supports and fund-raises for a CF cure.
CF has a higher incidence in populations of northern European descent, but there is no gender gap there. There is only a so-far unexplained difference in life expectancy that reduces the life expectancy of females surviving to adulthood, which creates the impression that this it mostly affects males.
It's not a cure and I think the idea is more like "It's an extremely expensive disease and a tiny number of people get it and if it weren't a predominantly Caucasian disorder, no one would be okay with spending this kind of money on it."
> if it weren't a predominantly Caucasian disorder, no one would be okay with spending this kind of money on it
It has nothing to do with race and everything with money. When ebola came to America, we didn’t find a vaccine because it was infecting white people. We funded it because it was impacting Americans.
That's not going to stop some people from saying "The white people are throwing money at this because it's a Caucasian condition."
Historically, male diseases got studied more than female diseases, probably having nothing to do with sexism per se. Most physicians and researchers were male, so they were interested in things relevant to their lives.
But that doesn't stop people from crying "Sexism!" about it.
> not going to stop some people from saying "The white people are throwing money at this because it's a Caucasian condition."
Some people will always say wrong things. I’ve found it helpful to focus on those who are speaking truthfully, and seeing if I can amplify or even help them.
It's not necessarily entirely wrong. Celine Dion is an advocate for the condition because one or more of her relatives had the condition (and died young from it).
"Coincidentally," she's white.
Celebrities somewhat often advocate for a condition they or a relative have. If it has a genetic component associated with a particular ethnicity, well, you are going to find people of that ethnicity advocating for it.
So it's not outright crazy talk to say the condition gets the amount of funding it gets because it's a Caucasian disorder.
It's unfortunate that it can potentially be spun as some form of racism. I long ago concluded that as someone with a form of CF, my "white privilege" includes a lifetime of suffering that most people will happily discount when hating on white people for historic racism.
We fight over an offence we did not give against those who were not alive to be offended.
-- Kingdom of Heaven
And in Take the Lead the main character says something like "Even if you can find someone to blame, it doesn't fix the problem."
Hating on whites doesn't fix the problem. Maybe someday we can find some other reaction to history and our unhappiness with it and our desire to have a future unlike our often ugly past.
One could point out that while funding often depends on social-political factors including age, sex, gender, and race. It's not necessarily a zero sum game either. Not to mention knowlege and technology used to defeat one disease often has applications to other.
Just the fact that Trikafta works probably will spur efforts to do something similar to sickle cell.
It occurs less often in other ethnic groups, but not rarely enough that the therapy should be considered irrelevant for them. The f***ked up part is that Trikafta's producer does not make it available to developing countries and tries to block generic alternatives.
Trying to mess with any part of the metabolism is going to have consequences.
You can even take a more direct route and make the body just burn more energy. Works perfectly well, technically doesn't have any side effects, though you have to take into account that burning energy results in heat.
And in all cases homeostasis is just going to attempt to return to normal as soon as possible. You need to somehow break the loop of your body wanting more energy to maintain its weight. This is a lot trickier because the checks and balances are everywhere and affect everything.
> You can even take a more direct route and make the body just burn more energy. Works perfectly well, technically doesn't have any side effects, though you have to take into account that burning energy results in heat.
Most weight loss treatments have terrible side-effects. GLP-1 is working pretty well as a target now, but all the other ideas didn't turn out so simple after all, and there were a lot of ideas for weight loss drugs
In my opinion orlistat (blocks fat absorption) isn't that bad if you actually follow the suggested low-fat diet. But if you're hoping to counteract a pint of ice cream, it's going to work tooooo well. The Public Relations was a nightmare... never stood a chance. The jokes were too good.
Acarbose blocks starch (and sucrose, to some extent) absorption. Instead of oily poop you get dry smelly gas that hopefully goes down over time. Starch & sucrose is not as big a part of American caloric intake as fat, but it can still help cut some of that out.
(Just sucrose. HFCS has glucose and fructose, which means sucrase doesn't need to work. Not a meaningful difference in most people considering how fast sucrase works, but when you block sucrase...)
Better idea: Focus on eating high nutrition, low cal foods (relatively speaking). Skip or limit the empty calories.
If you have CF, you become seriously ill in part because you are effectively seriously malnourished. I suspect many overweight people are also effectively malnourished and don't know it because their body turns the empty calories into fat.
if this actually worked, why so so many dieters fail? if this works so well, someone could make a diet program out of it, it would be super-effective and would sell billions. obviously easier said than done.
high nutrition, low cal foods (relatively speaking)
this is sorta contradictory. calories are nutrition.
From what I gather, dieters frequently count calories rather than tracking nutrients. If you are already deficient and try to limit your intake of food and it worsens your deficiency, at some point you are likely to spaz and stuff your face in desperation.
Except there are some weird feedback loops in the body, such as restricting calories leading to reduced calorie consumption, leading to less weight loss than expected.
The issue is this is like nicking an engine oil tube to decrease the car mileage. In principle it could work but you really need to nick the right tube at the right place. We have been nicking things everywhere for decades but finally with glp-1 and sglt2 inhibitors we found the right ones. A bit serendipitously.
Cystic fibrosis clogs the pancreatic ducts, which eventually causes irreversible damage to that organ. Because of that, many CF patients also develop diabetes. Sounds like a terrible way to downregulate the pancreas.
The high prevalence of CF in the white population was hypothesized to be due to the protective effect of being a carrier (heterozygous) of a CFTR mutation against typhoid fever, very common in Europe in the old ages.
> Vertex Pharmaceuticals is not making its drug, Trikafta, available in poorer countries, where thousands of diagnosed patients stand to benefit.
> The company is not trying to sell it, or allowing a local company to make it. Vertex is blocking potential generic competitors by seeking patents in numerous countries.
Such sensational prices eventually rain down on those paying for insurance though. In case of private insurance, it increases premiums. In case of public insurance, the taxpayer has to foot the bill.
It's easy to say that when it doesn't affect you but I had a childhood friend die last year from CF because he couldn't afford the medical treatments. He was using the various "public funding" sites to raise money but in the end it wasn't enough and he died.
I don't know what the solution is as it's a complex issue... but seeing someone young (in their 30s) die from something preventable because they can't afford the drug is perhaps one of the most horrifying and dystopian things I've seen in my life and makes me worried for our future. One presumably where the rich can live 50 years longer than the "poors".
The incentive is saving lives. That's what the researchers are in it for. The research is in large part publicly funded. Pharmaceutical companies are just charging rent on top of the discoveries.
The best argument you can make is that private pharma competes to improve manufacturing processes, but you world also have that in a 100% public system from multiple countries competing/collaborating with each other.
Like I said, that research is already publicly funded, and even if it wasn't it's always worth it to make sure people live longer as a country because more people means more resources to accomplish stuff with.
Why stop at medicine? Why does anyone get to have enforcable patents in "poor countries", make a profit, etc. etc. Do you also know people can buy the medicine in "poor " countries for free then, and just ship it back to the "non poor"?
What a ridiculously statement. Medicine is never for free. Best case is you have public health insurance, which spreads the cost across the taxpayers, or generic versions that cost less.
The problem you probably mean can be avoided by giving the license to selected companirs only, and gating access to the drug through healthcare providers.
I have CF and I was fortunate enough to qualify for Trikafta despite one of my protein mutations not responding to the drug. I have seen some great quality of life improvements from Trikafta like being able to go to the gym again, not being as winded climbing stairs, gaining weight, and having fewer lung infections.
However, Trikafta can't reverse the years of damage from CF, inflammation, and heavy antibiotics to combat nasty infections. I do experience some anxiety and mood swings and have developed recurring kidney stones since starting it.
Still, I am thankful that such a drug is available to me and many others like me. Maybe one day CFers will never understand what it means to have advanced lung disease.
Wow, to think that recurring kidney stones are better than what you were experiencing before. That’s incredible. Regardless, I’m glad you’re doing better.
It truly is remarkable, not only for the vast improvement in outcome for patients, but also the science.
The genetic defect that causes CF results in a chloride channel receptor being malformed so it it doesn't function correctly.
The fact they were able to develop a small molecule that perfectly fits within the defective receptor and then causes the receptor to change conformation so that it's now functional is absolutely remarkable.
Then layer on top the company has developed a few molecules that can address the different defects in different patients is really amazing science.
It's transformed a disease where patients die in their 30's or undergo a risky lung transplant (and still suffer other aspects of the disease after) to a more moderate, treatable disease where life span is normal is one of the great medical achievements of our lifetime.
Seems the Swedish government thinks Trikafta is too expensive, so it’s not available/subsidized in Sweden [1]. Must feel terrible to pay 70% taxes and being denied access to a drug that could save your life… :/
Bill Williams [1], perhaps best known for his 1983 game Alley Cat had CF, and suffered greatly because of the disease. He was 37 when he died. His book "Naked Before God: The Return of a Broken Disciple" is about his experience with CF and his faith.
The Digital Antiquarian has a well written article about Bill Williams' life [2].
In the near or medium future they will screen/crispr the germline so no one will ever have it. Yes it's eugenics but it will happen.
Edit: the ones downvoting me is it because you don't think it will happen, or because you don't think it's eugenics, or you think it's rude to talk about it?
Can do a blood test on the mother for Down's. Enough baby DNA leaks out into her bloodstream and you can see if the chromosome ratios are the slightest bit off or not.
I know what you're getting at, and it's a very difficult issue, but if you are advocating against screening out Down Syndrome then I disagree.
A question worth asking yourself is: If I had the power to give myself, or someone I love and want the best for, Down Syndrome, would I do so? Especially consider the case where the person is young enough not to remember life before the change.
I wouldn’t any more than I wouldn’t take away down from someone who was down. I’m not advocating about anything though, I am just stating the world is better with down people in it than without them. They are truly beautiful humans.
A close friend of mine worked in a "home" for people who had to fit all three of "adult," "violently disturbed," and "diminished mental capacity." They were not beautiful humans. While all types were present, the Down's crowd was just as nasty as the rest.
These folks get tucked away and the populace gets the high-functioning "nice" ones. Turns out that they're just as lousy as the rest of us.
No, but I also wouldn’t have ended our pregnancy had my daughter tested positive. I would have prepared for a different life, and I would have been happy if scared to be the father of a down kid. I’m not here to criticize anyone’s choices in their life - it’s their life. But I think we vastly under value down people. They have more love in their heart than an entire city of people without down. My friends brother was down and we spent a lot of time together, and I’ve since made a point of getting to know the down people I come across in life. They are truly the blessed amongst us.
I believe there are different degrees of it and being a parent to a severe case is a much more stressful life long commitment than being a friend to a mild case.
Yes you’re 100% correct. My friends brother was a severe case. It was not easy to raise him and he requires life long care. When the parent die I assume he will have to live in a home. He was non verbal and not self sufficient in most anything. Yet, he was always happy and kind, gentle, and loving. Even when things frustrated him he handled it better than I do now. But I will always remember his parents would discuss openly how blessed they felt that he had been born, and he seemed happy to be alive when I knew him. In some ways I think his parents also liked that when their other kids grew up and moved away Jeff was still there with them. As a father I selfishly can identify with that watching my daughter grow and knowing a day is coming when she will make her own way. Anyway, it is definitely complex - it was nice to read in the linked article some number of people are intentionally raising down children.
Eugenics is definitely a loaded term. It denotes good genes and of course everyone wants that. On the other hand it connotes a bunch of ugliness like culling persons with undesirable traits.
Everyone practices eugenics in the denotational sense after all. Nobody thinks “hey, I want to have children with this person that I think will give them bad genes”
Incidentally one of the major selling points of abortion is culling persons with genetic defects, which is absolutely eugenic.
Concur. I think this is likely to be controversial, and become an increasingly popular news topic and political wedge. (Maybe in the next few decades?) It seems that we can eliminate some genetic diseases through a combination of screening and embryo selection.
Screening is already very common. Offspring with unwanted genes can be screened off if mom is willing to abort (and if not, you don't typically bother with the screening)
I learned that from a medical lesson, it's just standard of care today
Carrier screening covers a really small fraction of pathogenic variants. It'll catch really catastrophic stuff but there's an enormous number of mixed-penetrance/AD variants that people pass on because they aren't lethal.
(plus, let's be real, most prospective parents don't carrier screen. only ones about to undergo IVF where PGT-M is sometimes an option.)
So this is a $300k/year medication but is apparently just (per the article) a combination of existing approved and developed drugs? As in the cost of development for this seems largely to be covered by the cost of development for the original drugs?
Is this behavior something that should be rewarded?
“Yay you found you could combine existing drugs to make something better but your charging as much as if you developed those drugs as well”?
Your cynicism might evaporate if you read the article carefully without jumping to conclusions and make an effort to understand some background of CF:
>“There was a lot of scepticism that this could be done,” Hadida recalls. ... The drug-discovery process required a marathon effort, testing the effects of more than one million compounds on isolated human lung cells to identify candidate drugs for clinical trials.
All of this research into these drugs was for the purpose of treating CF. They aren't developing drugs that target a CF-related protein in lung tissue to treat any other disorder. These drugs do not work on their own to any meaningful degree because protein function in the immune system is freaking complex.
Retraining proteins that are dysfunctional due to a genetic defect is not trivial stuff. They found a combo of drugs that allow a misfolding protein to function properly; two that when combined deliver the protein to the cell surface and then a third to get it to work properly once it is manipulated into the correct place.
CF also only effects a tiny percentage of the population. The only way the economics of this research makes sense is if they charge insurers a high price for it. If we don't reward this behavior, 70,000 people worldwide die at age 35 after having a medically miserable life. Instead they now have stunningly high chance of living until age 80 with significant quality of life improvement.
A friend works at Vertex and couldn't tell me for the longest time what the secret sauce was. The FDA approval was the only thing blocking their right to basically print money.
It's awesome people are benefiting from the drug, even if the money extraction schemes are dubious or marginally ethically ok.
Once we effectively deal with aging, and get to see 120+ yo people in 30s-like overall condition (and indistinguishable at a glance).
Aging in characterized in some 8 or 9 ways an old person is different from a young one. Each can be targeted and reverted, in a maintenance approach. Research organized by Aubrey de Grey is all about that.
It’s practically cured but people are still susceptible to lots of opportunistic infections and have a drastically increased risk of cancer on the medication so it’s really a stopgap.
At $25k per month per person that’s $30,000,000,000 per year for the 100,000 folks with CF. As a T1D I get it, but there is no way of escaping the other impactful uses of that sum.
Shame the life saving drug is rediculously expensive. I dont normally subscribe to bug pharma being greedy, but this one seems like a compelling case for that.
The canadian gov (PMPRB) tried to do sonething about that but i think they backed down
It's ridiculously expensive because it's a rare disease.
The total investment to bring this drug to market is in the range of hundreds of millions of dollars. Recouping that expense when there are only hundreds of patients in the US or thousands across the global requires a price that is far higher than normal medications.
Then layer on top the 1 in 20 chance that a drug actually makes it to market after that investment and the math starts to make sense.
> The total investment to bring this drug to market is in the range of hundreds of millions of dollars. Recouping that expense when there are only hundreds of patients in the US or thousands across the global requires a price that is far higher than normal medications.
So lets assume the drug cost 180 million to develop. There are currently 30,000 people with CF in united states. At the current price point they would recoup that cost within 2 months just from usa sales. This is a drug cf suffers would have to take for the rest of their life.
Its reasonable its more expensive than you average drug, but the $310,000 per year for these pills still seems excessive. Especially when its basically a death sentence without them so their customers are really held over a barrel.
"So lets assume the drug cost 180 million to develop."
The trouble is, you not only have to cover expenses for development of this, very successful drug, but also for 50 others that you never heard of, because they were duds, but the necessary trials still cost money.
Pharma is a numbers game. Most attempts fail, and you need to cover the cost of all the failures, otherwise you can't try out anything new.
It is possible that AI will help here, modelling drugs in virtual environments and recommending the most hopeful molecules. If it can be done, the ratio of failures to successes could improve.
There are currently 30,000 people with CF in united states.
This drug can only be used by CF patients with a specific mutation, not the entire population.
And I wouldn't assume $180M since this treatment is a combination of 3 different drugs all with their own development pathway and safety testing.
Then you need to look at the actual cost of manufacturing the drug, packaging it, delivering it to patients and all the salaries of the people it takes to do that. Sales of $180M is not profit, it's revenue.
Don't get me wrong, they are making a profit, but pharma company profit margins are usually in the 20-30% range and that's for the successful ones, not including all the companies that spend $100M and fail with nothing to show for it.
Then add on top the remaining patent life which is usually less than 10 years, after which the cost of the drug will plummet and the originator company will stop making money.
Tens of thousands of patients in USA, and given the massive longevity improvements, that count will go up. And add to that a likely increase in childbirths by CF patients.
People can save a bundle of money if they take advantage of the fact that it's a CYP-3A4 substrate, but I'm not going there and don't officially recommend this. But if you're lost in the woods and there's some grapefruits around....
I'm not sure how the accounting works out for Vertex, but they provide copay assistance even for high incomes. I have CF, and take Trikafta. I have an above market developer income, and I pay nothing for Trikafta due to their copay assistance (it's the only copay assistance program that's available to me, given my income)
Perhaps not unusually, but there is some evidence that they are more profitable than comparably sized non-pharma companies.
>"from 2000 to 2018, the median net income (earnings) expressed as a fraction of revenue was significantly greater for pharmaceutical companies compared with nonpharmaceutical companies (13.8% vs 7.7%)."
Profitability of Large Pharmaceutical Companies Compared With Other Large Public Companies
Before Trikafta, I usually had a 5+ day stay in the hospital every year, and sometimes I have would very stubborn respiratory infections that just wouldn't go away. I was mentally preparing myself for inevitable decline and eventual death.
Trikafta changed my situation dramatically. I've had no hospitalizations, and most the classic CF symptoms are either gone or extremely diminished. It can't undo a life of damage to things like my pancreas, vas deferens, etc, and I still take medicine to digest my food, but overall, it's as close to "normal" as I could hope for at this point.
The only real downside: weight gain. With CF the pancreas is blocked, so you lack in digestive enzymes, and it's a struggle to maintain a healthy enough weight to battle respiratory infections. After Trikafta, I gained some 30 pounds, and have a big belly on my small frame, and went up some 6 inches in the waist. To add insult to injury, it happened during the spring and summer of 2020, when buying clothes was a challenge due to the pandemic.
Speaking of the pandemic, the timing of Trikafta was amazing: it kept the normally full "CF floors" of hospitals empty, opening up those beds for those with COVID and keeping CF patients less exposed.
One side effect I should mention: many report extreme anxiety. However, I was starting an anxiety medication for the first time (something I should have done 20 years ago, but alas ...) and so those effects were muted or hidden to me.