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‘A game-changer’: How Vertex delivered on cystic fibrosis (statnews.com)
58 points by apsec112 8 months ago | hide | past | favorite | 22 comments

I never knew anyone with CF until college. Didn't even know how serious it was.

First day of the orientation, at our dorm I made a new friend who I later found out has CF. He would take medication and enzymes every day and do his CF treatment with the vibrating jacket. He seemed very healthy and energetic otherwise, except for the occasional cough.

I stayed in touch with him over the four years. I've witnessed him go to parties, sing, study, help his friends. He was always very public about how he has CF.

I remember at one point a mutual friend of ours told me "I really like him, I'd love to be in a relationship with him but chances are he won't be with us in a few years, I am not sure if I want to get myself involved knowing that's what's going to happen". I didn't think too much of it, maybe thought she was worried too much.

This friend went on to get a few great internships, first one nearby so no flight necessary but the second was in Texas, flying from Illinois to Texas a few times, he must have been exposed to some pathogens in during the flights and this guy whom I knew to have had his CF under control for 4 years, whom had his chance to "make a wish" and had his wish despite make a wish foundation dragging their feet for years hoping maybe he would die before getting his wish, as they didn't expect him to live this long to begin with, he basically worsened and passed away in 4 days, literally a few weeks after graduating college.

Not sure if the recent advancements would have helped but whenever CF is mentioned, I think of him.

He lived his entire life with doctors telling him he will die young or he won't live to finish elementary school, high school and then college. He finished college.

I find these stories enormously humanizing. We're here to beat the odds. Never surrender.

Exactly, let the cures march on. Its depressing when medicine looks to death as a solution. Seems like a copout and a failure to actually advance medical treatments.

The 14% number they give in the article is wrong in a subtle but very big way. They describe it as an increase in volume of 14%, but it's actually an increase in the FEV1 score by 14 percentage points. FEV1 is calculated by dividing the volume of air you can expel in one second by the amount they figure a normal healthy person could expel, based on your height, weight, and probably some other factors. So if you expel 50% of what a healthy person could, then your FEV1 is 50%. Trikafta increased that FEV1 value by an average of 14 points over placebo, in only a few weeks. That's massive.

I'm 32 years old, diagnosed with CF at 6 months old, and before starting Trikafta at the beginning of November, my FEV1 was 24%. (That's incredibly low. I was in the hospital on IV antibiotics, and we were all set to put me on the waiting list for a double lung transplant, when news of Trikafta came in and put the transplant on hold. At the time, I would get winded just by taking the trash down the hall to the trash chute, and would usually start hacking up a lung by the time I finished walking back to my apartment.) I go back to the CF clinic in just a few days to see just how much I've improved, but judging by just the way I feel now after about 2 months, I would not be at all surprised if I'm now pushing 40% for my FEV1. (And at the very least, I don't expect to hack up a lung after every pulmonary function test, which has been the norm for the last decade of my life.) If I go from 24% to 40%, that would be over a 50% increase in actual air flow volume. That's why this is a game changer.

The other big thing the article fails to mention is that the rate of exacerbations (which usually result in hospitalizations and a few weeks or more of IV antibiotics) dropped by about 60% over placebo. Exacerbations are where you see the biggest and sudden drop in lung function, so reducing the occurrence of those is really key to stabilizing our health.

Lastly, I want to mention that, while this drug isn't yet approved for children under 12, they're working hard on that. Theoretically, if a child were start taking this very early on, it's very possible that they would never experience any symptoms of CF. Unfortunately for me, I've had 30-odd years of CF that has permanently wrecked my lungs and pancreas (probably my bones too), but I still find it crazy awesome to think that I might be the last generation that has to deal with this.

The $311k per year price tag is still an unbelievably large amount, but the article certainly doesn't make any attempt to justify that price tag.

I can’t help but notice the $311,000 price. What if you are not covered by insurance?

If embryos are screened for CF in IVF..what happens in a natural pregnancy? Would it still be legal to terminate the pregnancy?

What about other countries? I understand life changing medications are expensive. But shouldn’t the govt just pick up the tab? Imagine we have universal health care...wouldn’t they just do it?

I believe they have a free medicine program for people without insurance and copay subsidies for people with it. It appears to be handled on a case by case basis (https://www.vertexgps.com/)

Many pharmaceutical companies (incl. Vertex) have patient assistance programs that are need-based. I don't really know anything about how much is covered under those programs those, maybe someone else with experience can chime in

Vertex has been playing hardball. They came to an agreement with Scotland last September and England in October, but other agreements are coming slowly. It is a real hardship for patients following Trikafta on Twitter and reading every day about gaining 30 points of lung function after only a few weeks, but not having the treatment available.

CF patients may have close to a normal lifespan with Trikafta, assuming that progress is made on treating some common infections, such as a pseudomonas aeruginosa. That means a lot of patients getting a very expensive drug for a very long time.

I have CF and have been taking Trikafta for just over a month. AMA.

So based on your profile blurb, you've obviously lived a fairly normal / successful life, at least career-wise.

The Wikipedia article for CF makes it out to be a pretty devastating disease.

What affect does CF have on your day to day life? How has this new medicine improved things? How big of a "game changer" is it really?

Broad questions, but I'm just trying to get some context here.

I feel like I live a pretty normal life. I have the most common mutation of the condition, which is typically results in the worst cases you hear about, but for whatever reason I've always had a mild case (I'm currently 42 years old, with 50-60% lung function). I grew up very poor and in a very immune-system challenging environment (in terms of cleanliness and I had parents who smoked indoors). I wasn't diagnosed until age 13 (most are at birth). I don't think I ever developed a sense of CF being the core of who I was, and I suspect that plays a role.

Day to day, I take a lot of medicine as second nature: breathing treatments, insulin pump, and pills to digest my food. I'm a smaller guy, and not very physically strong, and am just short of breath most of the time, so I limit anything that would be challenging like outdoor activity or manual labor. CF causes infertility in males, though my wife and I will do IVF. Like I said, I feel quite normal, though I suspect my chosen lifestyle is a product of CF, so of course it feels normal.

TBH Trikafta (and its predecessors) hasn't been a "game changer" as much as some incremental improvement, but others in CF groups I'm in have had greater improvements, so I suspect that's a result of where I started from.

If you're curious to the biophysics of this, the delta F508 gene is actually functional, but rejected by the endoplasmic reticulum because the ER fails to fold it correctly. It's possible that you have milder symptoms because your protein folding machinery is either more capable of folding the gene correctly, or alternatively, your protein checking machinery is more lenient.

With IVF, do you plan to do pre implantation testing to ensure your kids don't have/carry it?

I read that many embryos are a genetic mosaic, so testing just one cell as they currently do isn't as deterministic as people think.

Of course. We are seeing the IVF specialist my clinic recommends. My wife has been tested to not be a genetic carrier for CF; all embryos are screen for CF and other conditions before implantation.

Have you noticed a noticeable difference between Trikafta and the drug(s) that you were taking prior to this?

I took the precursor to Trikafta, Orkambi. It’s not a huge difference but I definitely feel better now.

Very cool, glad to hear it's working out for you!

What mutations do you have to the CTFR gene?

Double delta f508

Does this drug have a positive impact on the problems of CF other than lung function?

Many have weight gain. Those with CFRD (CF related diabetes) may produce more insulin naturally; both of these are due to less blockage of the pancreas, though the scarring of the pancreas (where cystic fibrosis gets its name) can’t reverse. Some women may have increased fertility (again due to less blockage)

I’ve gained weight in the month I’ve taken it (though just before that I lost 5-10 lbs due to an infection; so hard to say if I’m just returning to baseline). I do feel like my appetite has improved.

> Van Goor’s fix used cells derived from human bronchial tubes to test the potential of drugs.

Anyone know the back story on this detail? I wonder what cells specifically we're talking about.

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