Front Burner - New Alzheimer's drug met with hope and caution

Episode Date: December 1, 2022

Two pharmaceutical companies, Eisai and Biogen, have published the results of an 18-month human trial for their new drug, lecanemab. It's meant to treat people with early stages of Alzheimer's disease, a devastating condition that causes the majority of dementia cases and affects hundreds of thousands of Canadians. The results of the lecanemab trial are promising — the condition of people who were given the drug declined at a rate that was 27 per cent slower than those who were given a placebo. It's a glimmer of hope for those facing Alzheimer's disease, but questions about the new drug remain. Today, Mike Crawley, a reporter with CBC's health unit, is here to explain how the drug works and what it may mean for people living with Alzheimer's disease.

In the Dragon's Den, a simple pitch can lead to a life-changing connection. Watch new episodes of Dragon's Den free on CBC Gem. Brought to you in part by National Angel Capital Organization, empowering Canada's entrepreneurs through angel investment and industry connections. This is a CBC Podcast. Hi, I'm Jamie Poisson. Who is that? Who is that? Okay, who else? Hello.

Me. Good. This is your sister. This is you. Oh, I don't think so. This is you. Oh, I don't think so. This is you. Oh, so you remember them. What you're hearing here is an interaction between Vince Pankuska and his wife, Feli Dizon.

They live in Mississauga and they've been married for 20 years. The couple is flipping through a photo album, a lifetime of memories captured on film. But for Feli, who's 84, it's hit or miss. Some of the time she can identify her friends and family. Sometimes it's a blank. She's one of about 600,000 Canadians living with dementia. And that number is expected to rise to more than 950,000 by 2030. The most common cause of dementia is Alzheimer's disease. It's a progressive condition that destroys nerve connections in a person's brain,

leading to memory loss and making normal activity difficult and eventually impossible. Complications are often fatal. It's an absolutely devastating disease. The search for effective Alzheimer's treatments has gone on for decades. Until now, there's been no treatment for Alzheimer's disease. But now, a unique experiment is offering hope. So clinicians are cautious but find the idea of attacking inflammation promising. Early trials of a potential vaccine are going well. But a new study on the usefulness of Aricept says it isn't worth its high cost. But so far, nothing has proven to slow its progression.

That may be changing, though. A couple of pharmaceutical companies, Biogen from the U.S. and Japan's Acai, have announced a new drug called licanumab that they claim can slow early-stage development of Alzheimer's by 27%. The convergence of evidence across multiple measures of cognition, function, disease progression, health-related quality of life, caregiver burden, and biomarkers demonstrates that licanumab treatment may offer meaningful benefits to patients, care partners, and society. The announcement of the drug has sparked excitement, but also skepticism. CBC health reporter Mike Crawley has been looking into licanumab, and he's here with me now to talk about it.

Hey, Mike, it's great to have you. Hi, Jamie. So let's start with the two companies behind this new drug, Biogen and Acai. Who are they and what has the reaction been to their announcement? So Biogen is a U.S. pharmaceutical. Acai is a Japanese drug company. Their announcement is that they had this human trial involving 1,800 people who were at early stage or mild Alzheimer's. And this is a pretty big human trial. The study lasted a year and a half. And they found that the people who received this drug, licanumab, showed 27% less cognitive decline than people who got a placebo.

So when they first made this announcement back in September, it was just a press release and not full data. But even that, the stock markets really freaked out about it. They responded with massive enthusiasm. The share prices of both companies jumped more than 30% in a day. And to put that in dollar figures for you, Jamie, it added 11 billion US dollars to the value of Biogen in a day, 11 billion dollars. And Acai, they're a much smaller company, but even its value jumped by about 4 billion US. smaller company, but even its value jumped by about $4 billion U.S.

Wow. And just put this into context for me, because there are drug announcements all the time, announcements for new drugs all the time. So, you know, judging from this reaction, is it fair for me to say that this is really exciting news? This is being perceived as a big deal? Yeah. I mean, certainly the markets reacted that way, but it's also being perceived as a big deal. Yeah. I mean, certainly the markets reacted that way. But it's also being perceived as a big deal within the Alzheimer's community because, you know, they just have not been able to make progress in actually slowing down the deterioration that happens with Alzheimer's disease. So, you know, no treatment's ever been definitively proven to do that. And now finally, after so many decades of research and so many billions of dollars spent, here's a drug that appears to actually do just that. Mm-hmm.

And I want to talk to you more about, you know, what this purported 27% improvement actually looks like and how this drug actually, I guess, works. Maybe it would be best for us to start with explaining what actually happens to the brain when somebody has Alzheimer's. So the brains of people with Alzheimer's have abnormal clumps of a protein called amyloid and this protein uh hardens into plaques around neurons and and there's you know broad consensus in the field that amyloid has got some role in alzheimer's but there's a lot of uncertainty about exactly how like does basically it boils down to does does amyloid cause Alzheimer's or are these clumps of amyloid the effect of it? So that's the basics of what is known about Alzheimer's and these drugs target amyloid. And tell me, how does licanumab work, supposedly?

So licanumab is an antibody, a monoclonal antibody. It binds to the amyloid proteins and carries it away from the brain. So, it kind of functions in really, I'm really dumbing it down, it kind of functions like a vaccine does in some way. So it binds to the amyloid, draws it away from the brain. And there've been a lot of drugs that do this, okay? But no drug actually also slowed down the cognitive decline that comes with Alzheimer's. And according to their study, who did it work on? Like who's the drug for, I guess? So this is one thing that made this study, you know, particular is that they only enrolled people at the very earliest stages of Alzheimer's. So people had, who have mild cognitive impairment or a mild version of Alzheimer's disease. So not very advanced. It wouldn't work for people with severe Alzheimer's or fairly advanced Alzheimer's like Feli, who you heard from. It's more designed for the kind of people that they enrolled in the study. And I met one of them, a woman named Lorraine Klein.

I work three days a week. So where I work as a cashier, you have to remember vegetable numbers to put them through the cash. And there was one number I started to forget. I just couldn't remember it at all. I can't say I've lost a lot of memory because I'm pretty busy. But there's the usual thing that you'll go downstairs in the basement, you're going to go get something, and then you're there and you can't remember why you're there. You go to the grocery store, and unless you wrote something down, you might forget the key thing that you went to the grocery store

and go home and then have to go back. For decades, there have been these glimmers of hope when it comes to treating Alzheimer's. In the intro, some of those clips went back to the 1980s. Yet here we are in 2022 discussing what may be the first drug to actually help. Right. And so what are the questions you still have about licanumab? questions and concerns. So probably the biggest question is how effective really is this in terms of the real lives of people living with Alzheimer's? Like what does it actually mean to slow down cognitive decline by 27%? But some of the other questions that I think need to still be asked are things like, what's this drug going to cost? What's its impact in the long term? What are the potential side effects for things? So yeah, a lot still to come. I want to pull that apart with you a little bit. And let's start with what this purported 27% decline actually means. So the

way I understand it, and please correct me if I'm wrong, is that what would happen in the study is patients are tested on this 18-point scale. 18 is a severe case of Alzheimer's. And over the course of the trial, people who were given the placebo moved on average about half of one point further along the scale compared to participants who were given licanumab. And what does that actually mean, this half point difference in real life? As you mentioned, that was one of the questions you have. What does it mean for a person like Lorraine? Yeah, so it's a really good question. And I actually put that to one of the top scientists at ASI, the Japanese company, and he wasn't even really able to give me a tangible example of it. I've actually looked at

the questionnaire, the rating system that's used to rate the severity of someone's symptoms with Alzheimer's. And half a point on this scale is, for instance, going from no memory loss to having occasional memory loss, or going from being mildly unable to function on your personal care, high personal hygiene to being moderately unable to function. So and it's just it's just on one of these sort of six measures that are that are tested with that with that 18 point scale. that are tested with that 18-point scale. So a question that a lot of people are saying is, would a family member actually be able to notice the difference over the course of this 18-month period? The counter to this, though, Jamie, is that,

and certainly when you speak to people living with Alzheimer's or their family members, they see it as time, right? So you could think of that deterioration that happened over the course of the 18 months as being the people who got the placebo deteriorated sort of four or five months faster than the people who had the drug. And doesn't sound like a lot, but over the period of 18 months, people see this as buying themselves time. years or three years or four years, that the gain in function or the slowdown and the deterioration will be greater. You mentioned side effects too. What about possible side effects? Are people concerned about that?

So all of these anti-amyloid drugs have a tendency to increase swelling and cause bleeding within the brain. And, you know, this sounds kind of dramatic, but it is a thing that happens with a number of drugs that do things within the brain. that do things within the brain. The data showed that about 13% of the patients who received licanumab had some brain swelling. 17% of them experienced some brain bleeding. But even the brain bleeding happened even within 9% of the people who received a placebo. So these numbers proportionately compared to some other anti-amyloid drugs are actually a little bit less than the kind of side effects that we'd seen. The most concerning thing that has come out of the human trials were there are two cases of people

who died after receiving blood thinning or anti-blood clotting medication. So there is concern that there's the potential for interaction between blood thinner or anti-clotting medication and licanumab. So the company says that there's no indication that it's licanumab that caused these deaths, these deaths. But there certainly is, there are questions about whether its interaction with other medication could be potentially dangerous. Okay. You mentioned other drugs that are similar to this drug that have come before it. And can you tell me a little bit about those drugs? One of them is called Adjuhelm, right? So Adjuhelm is a drug that was actually developed by these same two companies, by Biogen and Acai. And the experience that the system had with Adjuhelm is one of the reasons why there was

so much caution around the Canamab. So Adjuhelm, when it came out, it got fast-track approval from the U.S. Food and Drug Administration. Controversial new treatment for Alzheimer's has been approved by regulators in the United States. The treatment, which is approved by the U.S. Food and Drug Administration, or FDA, is the first for the disease after nearly two decades of failed efforts. Even though the Food and Drug Administration's advisers warned against it, they basically said that Adjahelm didn't actually show benefit.

And all of this comes as the FDA itself phases investigations into its Adjahelm decision, which went against the advice of its own advisers. There's been a real mixed reception among doctors because of the lack of completely convincing data supporting whether the drug works. to market. And the hospitals and health insurance companies in the US, a lot of them refused to cover the drug because they said the benefit wasn't there. It wasn't just the cost, but the lack of benefit. And the company lowered the price, basically cut it in half. But even after that, the Medicare system in the US or the agency that runs Medicare refused to cover it outside of a human trial.

So basically, the drug Adjahelm was a flop. In the Dragon's Den, a simple pitch can lead to a life-changing connection. Watch new episodes of Dragon's Den free on CBC Gem. Brought to you in part by National Angel Capital Organization. Empowering Canada's entrepreneurs through angel investment and industry connections. Hi, it's Ramit Sethi here. You may have seen my money show on Netflix. I've been talking about money for 20 years.

I've talked to millions of people, and I have some startling numbers to share with you. Did you know that of the people I speak to, 50% of them do not know their own household income? That's not a typo, 50%. That's because money is confusing. In my new book and podcast, Money for Couples, I help you and your partner create a financial vision together. To listen to this podcast, just search for Money for Couples. Why is there a sense that lacanumab

is going to be any different here? So the number one thing is that it actually showed success in slowing the progression of Alzheimer's. It has a slightly different mechanism. So, you know, I told you about amyloid plaques being part of what goes on within Alzheimer's. Leucanumab targets amyloid at a different stage in the plaques growth. The best metaphor I heard for it is to think of, of, of amyloid like snow. Okay. So you get snow starts as water vapor up in the sky, then it falls as snowflakes and then it lands and it, and if you leave it sitting around, it forms snow banks that are pretty hard. Um, licanumab targets the snowflake stage, and other drugs have basically tried to go after the amyloid plaques once they'd already hardened into snowpakes.

So what lecanumab does is it targets it at the protofibral stage. So basically the amyloid is still soluble. It can be dissolved like a snowflake. is still soluble. It can be dissolved like a snowflake. And you mentioned price with Aju Home. Is there a similar concern with Licanumab? The companies haven't said what the price is going to be, but the chief executive of ASI did an interview with the Financial Times and was asked about the price and said, basically, there's no point in developing this drug if it's not going to get to patients. So we will price it at, quote, a level that is affordable. Right. So the cost of adjuhom initially was $56,000 a year. And so the idea is that that's untenable.

I would say it's fairly certain that it's not going to be that expensive, but it takes billions of dollars of research to develop these kinds of drugs. So it would be speculation as to what the price is going to be, but I think it is fairly safe to say that it's not going to be as expensive as that Adjahelm launch. Mike, I know you talk to a ton of outside experts about this drug, and how are they feeling right now about lacanumab? Do they think that this is the answer to Alzheimer's? Do they think it could be part

of the answer? Are they really excited about this? Or are they approaching it with trepidation? I think that there's a real mix, Jamie. I think a lot of researchers are excited about the possibilities. At the same time, they don't believe that this is a silver bullet, right? say that it's just such a complicated disease. And there's no one cure, for instance, for high blood pressure. And this Dr. Donald Weaver, who I spoke to in Toronto a long time, Alzheimer's researcher said the mechanism of high blood pressure is trivial if you compare it to the brain. The brain is the most complex entity in the universe, and arguably Alzheimer's is the most complex disease to the brain. The brain is the most complex entity in the universe and arguably Alzheimer's is the most complex disease of the brain.

So why would we think that there's going to be one drug that's going to be the answer to Alzheimer's? So the future of the field is likely some sort of combination of treatments. People talk about drug cocktails. Even the people behind the, the, behind licanumab say that it will likely be used in a combination therapy. So it's, it's definitely an advance and, you know, I've seen reaction all the way from, uh, there's some headlines that are saying that this is a monumental breakthrough and, you know, there's other headlines that are saying it, it shows, you reality where she has this disease that's expected to continue to damage her brain.

Even if she's getting licanumab, the best case scenario here for her right now seems to be their mind keeps working for a little bit longer than it would if she wasn't being treated for Alzheimer's. So Lorraine is quite active. She works three days a week as a grocery store cashier. She reads four books a week, she tells me. And she's, you know, trying to live her life very fully, but she's, she's got a lot of fear. In the beginning I was really afraid, really afraid, but hoping to be on this, hoping to get rid of what's in my head makes me feel a little better. You just feel more confident that you're in good hands. I've been married 54 years. I can't imagine, you know, not remembering him. We've been through a lot of things. So she's pinning a lot of hope on licaninab, hope that it'll actually have an impact. Yeah. All right, Mike, thank you so much for this. This was really interesting. I learned

a lot. And I know probably for a lot of people listening right now, this is an issue that they know firsthand, maybe from their parents or grandparents. And of course, I think it's something we all think about. It's sort of like a greatest fears thing. So thank you. You're welcome, Jamie. All right. So before we go, this drug has been submitted for accelerated FDA approval. The FDA in the U.S. has a January 6th response deadline. So that means that it's very possible that licanumab could be available south of the border as soon as January of next year. All right. That is all for today. I'm Jamie Poisson.

Thanks so much for listening. Talk to you tomorrow.