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.
(copied from the last time Trikafta was mentioned here: https://news.ycombinator.com/item?id=37540731)
He would take his enzymes, do the vibrating jacket treatment. He graduated and got a full time offer from a nice company. As he was relocating, he picked up some infection and passed away in a few weeks. None of us expected it. This was months before I heard of the approval of Trikafta.
My personal situation is probably pretty unique, in that I have CF as well, but had a double lung tx many years ago. A couple years ago my transplant team (actually it may have been the CF people.. fuzzy memory) asked me if I was interested in getting on Trikafta and after thinking it over for about 30 seconds I told them I'd probably pass. It seemed like it wouldn't have any beneficial effect on my lungs, as they no longer "have CF", and that I assumed it would just make extra weight for my decently healthy but still under par lungs to have to drag around. They didn't disagree.
>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.
I would have imagined that most people with CF already had extreme anxiety - wondering when the infection that is going to end one's life will arrive. Is it really possible that Trikafta is causing noticeably worse anxiety?
My best friend died of CF just a few years ago. He talked candidly about his eventual death, to the extent it was uncomfortable at first (but we ended up being to the level of making jokes about it, which I think was a positive thing for both of us).
He changed his WhatsApp status to a coffin and skull-and-bones emoji right before he went, just as a joke.
He didn't live with a shred of anxiety - least anxious person I've ever met. Dude was down for anything and everything, and could have probably fought off a bear despite being comically short and concerningly skinny. Easily one of the most kind and relaxed souls I've ever met.
There's a discussion of this in the article. Essentially, a bunch of people have said that they started experiencing extreme anxiety when they started Trikafta, and that stopping or lowering the dose helped immensely. However, clinicians have said that there's no actual evidence that the Trikafta is causal.
So it seems to be a bit of an open question and I'm sure an emotional one on both sides.
Funnily enough, although in practical terms my life is infinitely better than it was before the drug in, I would rate my anxiety as higher than it was before.
A lot more options open in the world, a lot more to hope/pine for, a lot more to lose. Back in the days when my expected future was to just hang out in bed, there wasn't much else to do than to just chill and read a book.
If anything he was a very mature guy for his age, having realized he has limited time but of course I wouldn't know the internal struggles he might have kept from us.
If you have anxiety over money, for instance, you'd probably still have it, regardless of whether you had $15,000 in your bank account, or $15,000,000.
Accutane was the best medicine I ever took. It resolved my acne (permanently) in a matter of weeks. I felt elated afterwards and never experienced mental side effects.
However, prior to the drug, I'd experienced several of the listed side effects, due to the acne itself and its devasting effect on my self-esteem.
For many teenagers suffering from serious acne, they'd also have mental side effects due to the skin disorder, meaning there would be a strong correlation between Accutane use and people suffering mental episodes. And if the wonder drug didn't cure the acne, as promised, I can imagine that failure might push some acne sufferers over the edge.
So, Accutane itself could be harmless, but the circumstances of its use might suggest causal link to mental side effects which are not causal at all.
This seems like a no-brainer way to treat obesity, by restricting or blocking such enzymes. Obviously the downside is diarrhea and other malabsorption symptoms, but obese people have too much nutrition. Blocking absorption seems easier than dieting, as no willpower required. You shit out the undigested food.
Hearing about any kind of advancement is huge. I can't even begin to understand what you've gone through, but am so happy to hear there is a new medicine to help with such a cruel disease and that it's made a world of difference to you. Sometimes it feels like medical science is still in the dark ages and I get saddened that we haven't got flying cars or Dr. Beverly Crusher can't wave some device over me and fix all the ailments I now have. Other days I hear about these kinds of advancements and it makes me smile!
So I just wanted to say: it was an impactful piece of writing, enough so that I remembered it quite clearly after a single read these few months ago.
Interesting. I'm an uncle to a family member with CF (and I'm a carrier) and one of their long battles has actually been weight. To the point of doing things like downing olive oil to try and keep up the weight. They've eventually had to take the fairly drastic measure of getting a feeding tube installed. Getting enough calories in just hasn't been possible until the feeding tube.
As I got older and into my 20s, I thought about him a lot -- it was understood that most CF patients don't make it out of their early 20s and I knew even if he were particularly lucky, as time went on and I aged, he was probably gone.
My father also recently died from lung cancer, and had a few months where he was effectively drowning in his own lung fluids, requiring doctors to drain his lungs with long needles through his back. That experience also brought me back to that schoolmate, considering what he had had to endure.
Recently, I was reorganizing my personal library and came across my elementary school yearbook and flipping through, saw his picture. It's been decades since he's likely passed on. It gave me pause to contemplate certain priorities in my life and try to cultivate greater compassion.
It's a particularly cruel disease, and this news is wonderful.
It seems like something every day reminds me of him. I’m really glad there’s hope for people with it. It’s a particularly shitty disease and he was the nicest most thoughtful person I’ve ever known. I miss him dearly.
Bittersweet. Glad there’s progress, wish it were earlier.
https://www.statnews.com/2019/10/23/we-conquered-a-disease-h...
In 2037 the patent will run out, and the generic price will likely be 90% less.
Fortunately, for Americans with good-enough health insurance, it's covered, so ... yay? For those without insurance, or in other countries where $300k is basically unaffordable, well bummer for you, you'll be the last generation to die of it.
I get the insane costs, and risks, of developing these things. I get that the profit motive is what drives there to be any research at all in pharma. I get that the price has to be high for everyone, or insurance companies will balk.
And yet, even knowing all that, there's a sour taste when we -could- (literally) save lives, but, well, money first ya-know...
I don't have an answer to this issue- there are downsides to all proposals I've heard. But this approach seems, well, pretty harsh.
[1] https://www.statnews.com/2023/11/03/trikafta-cystic-fibrosis....
They dragged it until he was 18. He always jokingly said "make a wish foundation is waiting, hoping I'll die".
He finally got to go Zorbing when he was 19. Passed away a few years later.
Not surprised the foundation jumped on Trikafta to remove eligibility.
> Recently, Make-A-Wish announced that children with CF would no longer automatically be eligible for the program, because “life-changing advances” had radically improved the outlook for them.
I know this is a long piece, but half the comments in this thread seem like people didn't even bother to read it before commenting...
We did IVF instead and to my surprise, 60% of viable embryos had CF, which I thought was unusually high compared to what I had been told prior to the procedure.
We were very fortunate that we did the testing and had successful IVF pregnancies, but so many other families aren't so lucky. I hope advancements in CF treatment will make it a non-issue for parents in the near future.
It is such a horrible disease and the breakthroughs are amazing. So many families will be much more fortunate than mine and I am happy for them!
The amount of development in the treatment of CF over the last 20 or so years is so incredible it’s insane.
It's a beautiful thing for treatments to be devised for rare conditions, to give people decades more life. It would be more wonderful still if we devised treatments for aging, the universal condition, to grant everyone decades more life.
Hardly anyone deserves to die. The vast majority of people are singularly incredible and worthy of life. They deserve to be equally safe from murder, fatal accidents, rare diseases like cystic fibrosis and the universal disease of aging.
Well, people are people. Somehow the life of a 90 year old is less worthy that than that of 20 year old. As to how they arrived at the magic number of 90 remains a mystery to the fictitious society where individuals routinely live for 9000 years.
Osteoporosis can make it so that a fall can lead to major fractures, which leads to a severe reduction in a person's independence. Macular degeneration can make an elderly person blind.
Neurological deterioration can take the form of conditions like Alzheimer's, where a person loses their memory of everyone they love.
The body, as it ages, becomes much more susceptible to other, terrible, diseases as well, like cancer, heart disease, and diabetes, each carrying its own set of debilitating effects that degrade quality of life.
I wouldn't use that analogy. It's more like breathing in a deep swimming pool or a very humid sauna. Slight physical exertion (like stairs or hills) can be like most people doing strenuous exercise. Laziness tends to be a way of life :-)
I friend of mine passed away a few years ago from it, and it was painful to watch slow degradation in his health over the years.
https://newatlas.com/medical/zinc-lung-macrophages-anti-bact...
Unfortunately, that's not guaranteed to bring a price drop. Humira is a good example of that; it recently went generic but much of the savings went to higher rebates to pharmacy benefits managers.
Some reading for anyone curious:
https://www.reuters.com/business/healthcare-pharmaceuticals/...
Humira is a monoclonal antibody (a biologic drug), not a small molecule. Biologics require cell culture systems and a completely different manufacturing process than small molecules, and are very complex drugs. The "generics" (called biosimilars) aren't significantly cheaper because they're simply very expensive to manufacture at scale. Humira or its "generics/biosimilars" will never be cheap. It's physically impossible with today's bio processing technology.
Trikafta is a mix of three small molecules, which are manufactured in large chemical batches and are the more traditional class of drugs. Many even have total synthesis pathways known which means you can basically make them by the train car scale for cheap.
When the patent on Trikafta runs out, it'll be very cheap.
I'll note that vanishingly few patients ever pay the full list price in the US--if you have insurance, the copay is small.
Your insurance pays (as they should, that's why you pay them premiums!). The company even pays the co-pay in most cases so the actual cost to patients in many cases is $0.
If you truly need it and don't have insurance, the company provides it for basically free with a patient assistance program, it's there on their website.
Kudos to the scientists who invented this, I don't feel bad for the insurance companies really, they charge their premiums and it's their responsibility to the policyholders to pay the applicable fees for care.
*edit: typo
In the online CF communities I'm a part of, I've never heard of anyone who couldn't get access to the medication (aside from the country they're in not approving it) (I'm in the US so my perspective is probably skewed)
https://glp1.guide/content/glp1-pricing-2024-02
Of course, insurers are struggling to not cover the bill, and although it's in the medicaid list it's up to states to choose whether to cover it or not
But the alternative, without the massive cashflows, is a world where the research never happens, and the diseases haunt us forever.
The Big Pharma treatments will eventually become public domain, and may inspire other cheaper treatments prior to that.
The fact that these conversations come up frequently is a symptom of the fact that Big Pharma is frequently doing fantastic things. Curing diseases that have plagued humanity for millenia and killed millions.
We have a very bright future. But the future is not free of charge, as we'll continue to require a lot of medical research, and medical researchers have families to feed, like the rest of us. Medicine costs money - there's no escaping it.
In the UK, we sometimes mistakenly imagine that our socialised healthcare system is "free." It's not. It's one of the most expensive in the world, and employs over 2 million people. The component of tax that I paid to fund the National Health Service was £8919 last year - the largest single expenditure of my taxes, and vastly more than I'd need to spend to get private healthcare.
So while American medical pricing is scary and sometimes ruthless, I think we need to put things in perspective and recognise their leadership in medical research - without which, we'd all be in a worse situation.
Hell, a lot of medical research is funded (in part) by public dollars, and then the results get locked up behind patents for years, which is gross.
It's a particularly touchy subject because it involves people's health and the ability/inability to pay for it.
But as a sufferer of a debilitating disease with a miracle drug that costs an arm and a leg, I've become a convert to the US pharma-industrial complex. These drugs take billions of dollars and decades to research--that funding/development isn't going to happen without venture capitalists who shoulder that risk for the profit reward. An equal number of pharma venture capitalists lose all their money, researching dead-end drugs.
I'm incredibly blessed to have both a cure invented during my lifetime and the means to pay for it. But even if I lacked the means, I would still infinitely prefer a world where a cure exists that I need to somehow access, as opposed to a hopeless world with no cure.
Since Trikafta is a blend of 3 small-molecule drugs, is it possibly feasible to publish a do-it-yourself synthesis process?
Or perhaps the community could even come together to set up a lab, where individuals could travel and go through the motions to produce their own?
I recognize this isn't ideal, but it might be legal...
> Or stopped being covered by insurance? Trikafta’s sticker price is more than $300,000 a year. Insurance typically covers most of that cost—minus what can be significant co-pays and deductibles—and Vertex offers co-pay assistance. But patients’ lives ultimately depend on decisions made by nameless bureaucrats in rooms far away: Insurance plans can suddenly change what they cover, and in 2022, Vertex announced that it would substantially reduce its financial assistance.
These drugs from Vertex started being approved in 2014. US insurers pretty much covered them from approval. Even Medicaid (health insurance for low income) started paying for it.
Other countries? The UK just started in 2020.
In Canada? Last I checked only 5 of the 10 provinces paid for it and only if you’re under 18.
The US healthcare is expensive for a lot of reasons, and one of them is new technology gets paid for really quickly.
(It's not "health insurance". Insurance covers unpredictable outcomes; needing a medicine every month for the rest of your life is not unpredictable.)
Which is good in the short term, correct? Long term people hopefully would be wise to settle for stable relationships, jobs etc...
Doctors told me they could think of only one other comparable breakthrough in recent memory: the arrival of powerful HIV drugs in the 1990s. Like Trikafta, those drugs were not a cure, but they transformed AIDS from a terminal illness into a manageable chronic one. Young men got up from their deathbed, newly strong and hale. ... This was a remarkable turn of events. But it elicited a complicated mix of emotions, not all of them joyful. Some patients who were no longer dying grew depressed, anxious, and even suicidal at the thought of living. This phenomenon became known as “Lazarus syndrome.”
Death is an end, after all. Life comes with problems...the writer Andrew Sullivan, who is HIV-positive, described life after the advent of the HIV drugs in his essay “When Plagues End”:
When you have spent several years girding yourself for the possibility of death, it is not so easy to gird yourself instead for the possibility of life. What you expect to greet with the euphoria of victory comes instead like the slow withdrawal of an excuse. And you resist it.
The intensity with which you had learned to approach each day turns into a banality, a banality that refuses to understand or even appreciate the experience you have just gone through.
Now, the forums are overrun by small numbers of constantly online members who feel the need to dominate every conversation. The content has become almost entirely venting and memes, with an unreasonable amount of alternative medicine being pushed as fact. It’s understandable that they’re frustrated, to say the least, but the way their frustration gives way to a communal rage against doctors has weirdly opened doors to alternative medicine peddlers. It’s disgusting to me to see how the alternative medicine pushers have arrived with open arms and comforting smiles for vulnerable communities, which slowly becomes a sales pitch for their products.
I’ve seen everting from people peddling custom diet consulting based on your 23andMe results to invitations to private, paid Telegram channels where they supposedly share their secret cures, to doctors from Eastern Europe who claim to have cured the condition (which has eluded many researchers and pharmaceutical companies) with a custom treatment made from the patients’ own urine. The way these communities set themselves up to rage together at modern medicine opens the door for friendly alternative medicine scams.
It’s depressing.
Source: have CF.
If you eat a tub of ice cream as dinner, you're going to have a bad time.
Of course, it's Canada, so you may have private drug coverage and then it depends on province whether you fall back to the public coverage if the private payor doesn't cover it.
> The third-generation of modulators, Trikafta, is a new transformational drug that can treat up to 90% of Canadians with cystic fibrosis. Trikafta was approved for sale in Canada on Friday, June 18th, 2021, by Health Canada for people aged 12 and up with cystic fibrosis and at least one F508del mutation and on April 20, 2022 for those aged six and up. As of September 13, 2022, every province, territory and federal drug program is funding this drug for those six and up. Unfortunately, it is not accessible to all who can benefit from it, and therefore our advocacy work continues
https://www.cysticfibrosis.ca/our-programs/advocacy/access-t...
Aging is the gradual accumulation of cellular and bodily damage. Nothing would do more for human health than having effective treatments for arresting and reversing that degradation.
Insurance companies are starting to say they wont cover name-brand Humira without a strong doctor's note.
Still, the price of the drug went down from being completely unaffordable without insurance to the price of an car payment. It's still expensive, but much better than before. You're not as tied to your company providing good insurance, for example.
But, if someone is selling a system which doesn't exist yet, but is supposed to be better, but that will only work if we also shut off the one working system first, before knowing... well, I'm skeptical.
It's easier to corrupt one or two government officials than it is the entire international capital marketplace.
Obviously there is a limit to how much spending the public will support, but I don’t think it’s a complete nonstarter.
[0]: https://www.pewresearch.org/short-reads/2018/07/03/americans...
So now you have some willing participants you have to screen your initial group to filter it down to people who actually meet your recruiting criteria and consent them for your study. Finally you actually get to gather your data, if you need people to come in for sampling and have to cover their expenses.
Next you'll look at your data and realise there's some confounding effect which reduces your powers to infer anything (e.g. somehow you overrecruited a particular group and they turn out to do something which correlates with the thing you're studying). You'll cry a little and realise you need to recruit more people to have any statistical power to draw a conclusion.
tldr; medical and scientific studies are hard if you want them to actually have any validity.
By 'indefinite/active studies' I mean that the studies never stop - data just keeps going back into the system as a flywheel of the drug distribution process. I take a second-generation drug for CML (leukemia) and none of my health data goes back into research unless my doctor decides to elevate my data into a paper or something (which I don't think has happened yet).
so, what I'm trying to say is that for this particular drug we "just need to wait", no?
I’ve lost most of my money anxiety, but it took a lot of purposeful work inside myself to achieve that including years of daily meditation and intentional study of Buddhism. Before that my money anxiety was unbearable. It didn’t matter how little or how much I had, because it wasn’t about money in truth. It was a fear of losing control and other things like self worth and identity issues as a result of my earlier life. As I learned to let go of the self and my identity and live life as it is rather than what I’m afraid it might be I’ve lost my fears, not just about money but all of them. In my experience lack of money instigated my anxieties but once they started it didn’t matter how little or much I had.
That said it drove me to get more and more, and I enjoy having more than when I had none. But even if I lost it all I would be ok now.
In all seriousness, you can buy the APIs directly from China/India and compound them yourself. It's easy and dirt cheap, in most cases. This is typically how underground steroid labs and other illicit pharmacies work. It's in some cases how legitimate compounding pharmacies work.
So how do you know what you're getting is pure, or even real? Simple, before shipping it to the US, you send it over to an analytical lab in China and have them run GC/MS or LC/MS on the chemical raw material. Since it's supposedly a pure compound, that should be easy, and there's very rarely any ambiguity as to the results. This also ensures that you're not inadvertently importing anything on the DEA's scheduled list.
I assume communities exist on the Internet for this kind of "drug piracy"?
Nootropics were a pretty popular trend around the same time, and I knew a lot of guys who would import weird drugs and peptides from Russia and China. It's the same sort of procedure I outlined in my last post, in that you're ordering drugs or drug-active-ingredient-powder from abroad... And then hopefully testing it.
Roughly 10 years ago, when [redacted breakthrough drug] was released, I helped some friends set up a pirate pharmacy. Those were good times.
And so (1) there's often a disproportionate focus on doom and gloom rather than success stories, which paints a pessimistic picture for anyone joining after a recent diagnosis, and (2) the most prominent voices have a wounded-cornered-animal mentality that makes them defensive and/or prone to lashing out. And I can't totally blame them, given how hard it is to live with a treatment-resistant chronic condition, but it's not the most constructive environment for everyone else.
I also had a quick look into the social media (primarily reddit) aspect of these vascular conditions, and it's a pile of dogshit. Most of these patient communities bill themselves as "support groups", but there's never any real discussion on meaningful research, drug, or device advancements. They places serve primarily as "pity pits" for chronic moaners and scammers selling alternative medicine.
No, I was a total loser in high school. I barely graduated and had awful test scores and did no extracurricular activities other than smoke pot.
My grandparents bought me a computer when I was young, I think because my mom saw how much I was interested in them. It was a c64, but had no storage devices so I had to type in programs from scratch each time which was a tall order for a 6yo, but I did it anyway. At some point someone gave me a 486dx2 board that was an extra and I built my first Linux box running 0.96. My schools also had an internet connection and I could get dialup access to some sunos boxes and some NeXT boxes in the library when I was in high school. One of my greatest wishes growing up was to have enough money to have the best monitor since my monitors were always garbage. My house now has nice TVs and monitors everywhere LOL, but they’ll never hold a candle to my first VGA monochrome monitor I delivered papers for a year to buy.
there were no middle schoolers optimizing their resumes for how to get a Jane Street internship in 8 years bc Jane Street was only a few years old. same for a lot of other firms.
Also at that time, as you say, there wasn’t a broad cultural awareness of the money to be made in quantitative fields. In fact this was the era of Revenge Of the Nerds movies and glorification of the idiot jock getting a business degree and the passionate nerd being the butt of the joke. You really only went my route if you were a total fuck up loser. Now the social view of things has completely pivoted.
I would say interestingly the middle school kids optimizing their resume only make it so far in industry. They’re never really passionate about what they’re doing they’re just laddering. At some point they shift to management or product or something. At the top firms though the people who really make the money and whose opinion has ultimate power are the fuck up losers who live and breathe their passion and would do it for free if that’s all there was.