The Decibel - The drug giving new life to cystic fibrosis patients

Episode Date: March 3, 2023

For years, a diagnosis of cystic fibrosis has often meant an early death for patients. This week, Cystic Fibrosis Canada released its annual data report this week for 2021. A new drug, Trikafta, is keeping patients out of hospitals and off of transplant lists.The Globe’s health reporter Kelly Grant explains why doctors are now talking about cystic fibrosis as a disease in transition and the hope of a new future for thousands of patients.Questions? Comments? Ideas? Email us at [e-mail]

Cystic fibrosis used to mean an early death for many patients. But a new report released this week from Cystic Fibrosis Canada shows how things have changed since a new drug, Trikafta, became available here in 2021. Hospital admissions for lung infections are down by a third, and lung transplants are down more than 60 percent. Patients are seeing life-changing results. Kelly Grant is a health reporter for The Globe and Mail, and she'll explain how this drug is giving people a chance to consider a new future for themselves. I'm Manika Raman-Wilms, and this is The Decibel from The Globe and Mail.

Kelly, it's great to have you back. Thank you so much for being here. Glad to be here. Let's just start with the very basics here. What is cystic fibrosis. So cystic fibrosis is an inherited illness where a genetic mutation sort of impairs the ability of a critical protein in the body to work the way it should. And that sort of faulty protein leads to all kinds of organs in the body being filled with a sticky mucus. So that mucus disrupts fertility, it disrupts the digestive system's ability to absorb nutrients. And the symptom that probably most people who've heard of CF would be most familiar with is that it clogs the lungs. And in clogging the lungs, it leads to things like severe chest infections, difficulty breathing,

and ultimately it is the cause of deaths for people with CF. I think a lot of people may have heard kind of the metaphor essentially of kind of drowning on the inside. Yeah, it's a really evocative and I think pretty accurate description. It was used in a television ad for the cystic fibrosis group back in, I think, the mid-2000s. I remember seeing the ad growing up. Yeah. And how common is it in Canada? So it is considered a rare disease, but among rare diseases, it is one that has one of the largest numbers of patients. So there are right now about 4,300 Canadians who are diagnosed with CF. Okay. And from what I understand, Canadians who are diagnosed with CF. Okay.

And from what I understand, people are usually diagnosed as infants these days. And so until a few years ago, what would it have been like for, I guess, for parents to receive that kind of diagnosis for their child? Yeah. So now the reason why it is usually diagnosed in infancy is that all provinces now look for CF on newborn screening. So for those of you who've had babies, that's when, you know, the doctor or nurse will come in and prick your newborn's heel, and then they test for all kinds of different childhood disorders. And CF is one of those ones that's identified now. And so, you know, the conversations that doctors used to have with these patients were that, you know, your child has a very severe life-limiting illness and that the median age at death would be somewhere in, say, the late 30s. Now, that's gotten better over time, but, you know, that kind of news for parents to absorb is incredibly difficult.

Yeah, yeah. I mean, I can only imagine that would be an incredibly difficult thing to hear about your newborn, right? Now there is this new drug, though, Trikafta, and it's been available in Canada for almost two years now, not quite two years. So we're actually starting to see more data about the effects of this drug. So Kelly, how has that actually changed things? So it's changed things really dramatically. People in the CF world now refer to the disease as a disease in transition. The idea being that this was a severely life-limiting fatal genetic illness. And now with the use of this modulator drug, as it's known, and similar modulators that have come before it, now they're talking about

this as a treatable chronic illness. And the outlooks for people who have CF have changed dramatically. Wow. Okay. So very significant there then. Yeah. So it covers almost everybody. Now, there are about 10% of patients whose genetic mutations mean they're currently ineligible for Trikafta. And so that has been very difficult on that smaller group of patients who's now watching all of their sort of friends and colleagues in the CF world start to really feel much better and they're a bit left behind. Yeah. Well, let's actually get into some of the details here then about how this drug actually works and what it changes for people. So what does this drug actually do? So it's a combination of three chemical compounds. That's why it's referred to by some people as the

triple therapy. And what it does is it makes this critical protein that I talked about earlier work better. And when that happens, it thins the sticky mucus that has been clogging all of these organs. And so the results are that within a couple of days or weeks of taking the drug, depending on the patient, a lot of patients experience something called the purge, which is where as the mucus thins, they cough up like quite a bit of sort of disgusting material from their lungs. And then they find pretty quickly that they're starting to breathe better. They're not coughing. And for people who have CF or have grown up in a house with somebody who has CF,

the constant background of their lives is endless coughing. So to have the coughing go away, people really notice. And then people are putting on weight. You know, CF has been traditionally a disease of malnutrition. You know, very early on, you know, decades and decades ago, kids died of CF in part because they just couldn't keep weight on. Because of the mucus kind of coats your digestive tract, essentially, so you can't absorb nutrients. Yeah. And also a lot of CF patients are really quite nauseous and so then don't have much of an appetite. Now, over the years, the malnutrition problem really improved as doctors discovered that a combination of a high-fat diet and having patients take a ton of enzymes with their meals helped with this absorption. So before Trikafta, survival was increasing quite steadily for CF patients.

And one of the reasons for that was the sort of discoveries around the high-fat diet and the enzymes. Okay. So it sounds like it actually takes effect pretty quickly. You said a number of days or weeks for people to actually see the effects. Yeah. What I was going to say earlier is that another one is, of course, weight gain, right? Which for patients who spent their whole lives kind of desperate to keep weight on, this has been a real change. In fact, now, the CF patient registry is tracking really for the first time sort of concerns that people with CF

are having about experiencing being overweight or even obese because the drug has changed their ability to put on weight so substantially. It's also seeming to have a pretty substantial effect on women's fertility. Women with CF are fertile and can conceive, but it is often very difficult because of that sticky mucus we talked about, which sort of acts as a barrier for sperm to get into the woman's body where it needs to go. But with this drug now, we're seeing a bit of a baby boom in terms of kids born to women with CF. Wow, that's amazing. So these are really life-altering things that we're talking about here.

Very life-altering. One of the neatest things I found when talking to some of the doctors who treat CF patients was talking to doctors who had been involved in the trials for Trikafta. And both the patients and the physicians are blinded to who is getting the real drug and who is getting placebo. In this case, they always knew almost right away, okay, this patient's getting the drug and this patient's getting placebo because the difference was so dramatic. We'll be back in a moment. So, I mean, this sounds like pretty incredible results that we're hearing, though. I mean,

I have to ask, though, what about the other side of things? Are there any side effects from taking this drug? So one of the things doctors are watching is tracking patients' liver functions, although those concerns seem to so far be pretty minor. Some patients do develop a rash, but that does seem to go away with some time. Overall, the concerns really when I spoke to doctors seem to be more about two things, and that is the 10% of patients I mentioned who are currently ineligible for Trikafta and some concerns around the cost of this drug. And I want to get into both of those because those are both really key things. Who can take this drug? You said this is a disease for kids and adults right now, but who's eligible to take it? So the drug is approved in Canada for

everyone who's age six and up with at least one copy of something called the F508 del mutation. And so like you said, 90% of people with cystic fibrosis are eligible for this. So what if you are one of the people in that 10% though who aren't? Well, I think first of all that it's really emotionally hard. The CF community in Canada is really a pretty remarkable group of patients and families, and they run big fundraisers, they are sort of supportive and cooperative. And I think for those patients who are left behind, it's been very difficult for them emotionally. Now, there is some hope for those patients. There's one research project at Sick

Kids Hospital in Toronto I'd want to point to, and that is one where they are trying to take basically the cells of some patients who have a different kind of mutation and, you know, in the lab test to see if they respond to Trikafta as well. So there is a chance that some of the existing 10% who are left out, it may turn out that Trikafta works for them as well. But it's very tough because with so few patients, there is, I think, less interest from pharmaceutical companies to pursue trials when you're talking about such a small group of patients and there's so little money involved doesn't mean it's not happening. It is, but there's not the same sort of drive that exists when you're dealing with a decently large market of patients. So, I mean, in a kind of crass way of thinking about it, pharmaceutical companies will make more money if they're selling a drug to 90% of people with this disease instead of the 10%.

Yes. So one of the big issues you mentioned, Kelly, is the cost of this drug. So let's talk about this because Trikafta is a really expensive drug. $300,000 a year is what patients in Canada are looking at. How do people afford that? All right. So as far as I know, there's nobody who's paying $300,000 out of pocket. So first of all, that is something that's called the list price. So that's the sort of sticker price for the drug. We know it's really common in the pharmaceutical industry for them to negotiate confidential discounts with payers for drugs. So in the case of Canada, there's one central office who negotiates these discounts on behalf of every province and territory.

So my understanding is that the drug costs less than the sticker price, but we have no idea by how much because the pharmaceutical companies really guard that information very closely. Then every province and territory does cover this drug. In my time covering pharmaceutical policy, I really can't recall a very expensive drug like this going through the system to get added to the list for each province quite as quickly as Trikafta. And I mean, I think the big reason for that is that so often expensive pharmaceutical interventions cost a lot of money and make a minor difference in the lives of patients. In this case, because the outcomes have been so good and so dramatic, and the alternative is, you know, a lifetime of being in and out of hospital and then probably a lung transplant, those interventions are really expensive too. So this is one of those cases where

the cost-benefit analysis really came down pretty easily in favor of Trikafta. That being said, there are still some patients who do struggle to afford this, and that is because we don't have a universal pharmacare system in Canada. So if you're a person who has private insurance, then generally before you can go to the provincial programs, you start off by trying to go through your private insurer and your private insurer might cover Trikafta, but maybe your particular workplace plan has an 80-20 split where you pay 20% of the cost. And if we're talking about a $300,000 a year drug, that's a ton of money, right? So there's that. And then also the

provincial plans, even though all of them do list and cover Trikafta, each province's catastrophic cost drug plan has slightly different details. So in Ontario, for example, their program has a copay that's geared to income. So if you are middle class or well off, you might have a very substantial copay every year and that can be difficult for patients. Okay. Okay. So it depends a little bit on your specific situation, but it sounds like people in Canada,

there's some access to it there. But is the drug available elsewhere? Like, I'm thinking specifically of people in poorer countries. Do they have access to this? So it's generally not available in lower income and poor countries. And that is because the company that makes Trikafta Vertex has elected not to sell it in those countries yet. And the thinking among pharmaceutical experts is that that's a bit of a strategic choice on the part of the company, because they would likely be

forced to sell the drug at a much lower price for any patients to be able to afford it in those countries. And that might undercut their ability to charge such a high price in richer countries. I want to touch on something that you mentioned a little bit earlier, Kelly, which is lung transplants. Because it sounds like for a later stage of treatment for cystic fibrosis, this is what a lot of people end up having to turn to. With this new drug and with the changes that are happening with it, I wonder, have we seen any difference in people actually needing that kind of later stage treatment? So one of the most exciting things about what's happening with this drug is it is leading to people who've been on the active transplant waiting list being taken off that

list. So the Canadian Cystic Fibrosis Registry, which put out this report earlier this week with 2021 data, for the first time in 2020, with the arrival of this drug, they actually started tracking who was being removed from these active lists. Because prior to now, like getting on the transplant list was a one way street, right? You just didn't come off unless you died or got a transplant. So as of the end of 2021, they know of 12 people in Canada who have been taken off the active transplant waiting list. And just to clarify, being on the active list would mean you're at the point where you're carrying around basically a pager so that if a set of lungs becomes available, you can go right to the hospital.

So it sounds like this drug is actually changing. Even at people at later stages of this disease, you're actually seeing a drastic difference here. Yeah. One of the doctors I spoke with in BC, who is the medical director of a CF clinic there, said that at this point, the only people he knows who are active on the transplant waiting list with CF are those who have the mutations that make them ineligible for Trikafta. Wow. So doctors say this drug, this is a treatment, but it isn't a cure. So where does cystic fibrosis research go from here? So the big holy grail is really gene therapy. The idea being that, you know, can they come up with a one-time therapy that actually corrects the underlying genetic defect that causes the

protein to malfunction? So there is still lots of research going on around that question, and it's still the ultimate goal of researchers who work on CF. Before I let you go, Kelly, I just want to ask you about some of the people that you talked to that had their lives, it sounds like pretty drastically changed with this drug. They maybe, you know, learn they had more years ahead of them than they thought they would. So I wonder what you heard from people who are in that position.

Yeah, it was really remarkable to talk to CF patients who have seen their lives and their futures changed so dramatically by this drug. I just want to first point out that in this most recent report, the median age at death for people with CF in 2021 was 38.7 years. So that means half of all people with CF dying before their 40th birthday, right? So if you are looking at a future where, you know, you don't expect to live into retirement or old age, then you might live a different kind of life. So people have, you know, not invested in RRSPs, maybe not necessarily gone to post-secondary education, chose not to marry, chose not to have kids. And this is really, this change in their prospects has really like thrown some people for an emotional loop. It's mostly really great news, but it's been like a bit of an existential crisis for some CF patients, as one doctor put it to me. Now, for the patients I spoke with, they mostly, well, entirely were sort of thrilled at the change in their health.

And, you know, one of the most moving interviews I did was with a woman named Marie-Pierre Amri. And she's a Montreal lawyer. And, you know, she'd often kind of thought in the back of her head about someday becoming a mother, but really like wouldn't let herself go there because she knew about the difficulty that women with CF have conceiving. There was that, but there was also just the fact like, you know, am I going to bring a child into this world that I'm not going to be able to take care of in the long term? And that was always a big thing for me. Anyway, she went on Trikafta. About six months later, she got pregnant. And in February, she had a healthy baby girl. Wow. That's amazing. Really life-changing there. Kelly, thank you so much for taking the time to speak with me today.

Thanks for having me. That's it for today. I'm Mainika Raman-Wilms. Our producers are Madeline White, Cheryl Sutherland, and Rachel Levy-McLaughlin. David Crosby edits the show. Adrian Chung is our senior producer, and Angela Pachenza is our executive editor. Thanks so much for listening, and I'll talk to you next week.