Short Wave - A New Drug For A Relentless Brain Disease

Episode Date: October 5, 2022

ALS is a disease that destroys the nerve cells in the brain and spinal cord we need for voluntary movement. There is no cure, but now there is a newly approved medication that may slow down the disease and extend patients' lives. The drug, called Relyvrio, got its start with a couple of college students, some "ice bucket challenge" money, and a new approach to targeting this disease. Neuroscience correspondent Jon Hamilton checks in with host Emily Kwong about why some advisors aren't persuaded the drug works and how you weigh promising but limited evidence against the backdrop of a 100% fatal disease with hardly any other treatment options? See pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences.NPR Privacy Policy

You're listening to Shortwave from NPR. Hey, shortwavers. Emily Kwong here with our resident brain correspondent John Hamilton, J.J. Hammer. You're here to talk about some good news from the world of ALS research. John, let's start with defining ALS. What is it? ALS or amyotrophic lateral sclerosis is also known as Lou Gehrig's disease. And the way a lot of people know it, Emily, you might remember this, is the ice bucket challenge.

Oh, yes, those viral videos. of people like dumping ice water onto their heads to raise money for ALS research. Exactly. That's the disease we're talking about. It gradually destroys the nerve cells in the brain and spinal cord that we need for what scientists call voluntary movement. So the cells that control the muscles that allow us to walk and talk, to chew food, to swallow, even to breathe. About 6,000 people a year in the U.S. are diagnosed with ALS and most of them die within two to five years. It is a disease with a really devastating prognosis. So what is this new development? What the potentially good news is that the Food and Drug Administration has approved a new drug for ALS. It's called Relivrio and it appears to slow down the disease.

What that means is that the drug may allow people with ALS to live five or six months longer than they would otherwise. And why the hesitation you said potentially good news? Yeah, because scientists are still trying to figure out, just how effective this drug really is. It was approved based on a pretty small study, just 137 people with ALS. And we won't really know what the drug can do until we get the results of a much larger study, and that's a year or two off. Now, ALS, it's a terminal diagnosis. And even just having a drug on the market, even the possibility of one, must be encouraging for patients. Absolutely. Right now, there are only a couple of drugs for ALS, and they have a pretty modest effect.

So this could be a big deal. I talked with Kalanid Balas. She's the president of the ALS Association, which helped fund the research on this drug. Here's how she talked about the prospect of extending people's lives by even six months. Six months can be someone attending their daughter's graduation, a wedding, the birth of a child. These are really big, monumental things that many people want to make sure that they're around to see and be a part of. Today on the show, the unlikely story behind a new drug to treat ALS. You're listening to Shortwave, the Daily Science podcast from NPR.

A quick shout out to all of our Shortwave Plus subscribers. Thank you for helping to support our show. Subscribers get sponsor-free versions of our episodes and our immense gratitude. You can learn more and sign up at plus.npr.org slash shortwave. John, you have been following the story of the development of Relivrio, this new ALS drug for a while. Where does it all begin? It begins at Brown University, so Providence, Rhode Island, nearly a decade ago. There were a couple of undergraduates there named Josh Cohen and Justin Klee.

They realized there were basically no drugs that could stop diseases like ALS. And they felt like most of the research had been focusing on the very earliest stages of these diseases. So they thought maybe it was time to look at a drug that could help people later on, you know, when they already had symptoms. What's kind of amazing is that while they were still in school, Josh and Justin actually formed a company to make their idea happen. They named that company Amalix. And I got a chance to talk to them about it just a couple of years ago when the idea was starting to take off. So Josh and I started Amelix in 2013 around what we saw as a new approach. for neurodegenerative diseases.

So diseases that cause nerve cells to die. You know, that includes Alzheimer's and Parkinson's and, of course, ALS. Yeah, some of the most serious brain diseases we have. And it's pretty amazing these two undergraduates decided to tackle this. What was their idea for treatment? Well, they wanted to come up with a drug that would help keep nerve cells alive, you know, even when these cells are under attack, right? Help protect them.

And they thought they could do this by using a combination of two existing products. One is a naturally occurring substance. You can buy it online. The other is a prescription drug that's used to treat babies with this rare metabolic disorder that affects their kidneys. Okay. And how do these two products work together? Well, like a lot of drugs that have been approved, it's not entirely clear. But the thinking is that this combination of drugs does things along these lines. It probably increases a cell's ability to tolerate stress. And maybe it keeps a cell from going into this self-destruction mode. It may also help proteins in the cell keep the right shape, keep them healthy. But John, I know that drug companies, they test ideas

like this out all the time. How do a couple of college students even start to do this, like fund a drug development project? Josh and Justin say they got a lot of help from faculty members at Brown and then from other advisors who took an interest in their idea. They obviously couldn't have done it just on their own. But they still had to do a lot of fundraising. And the way they described the process is that they would find just enough money to pay for like one little study. Then based on the results of that study, they would go back and raise more money to pay for the next little study. And eventually they got this grant from the ALS Association. And remember that ice bucket challenge?

Greetings all. This is Kermit the Frog coming to you from the hot sticky swamp where I'm Oh, and elementary, are you ready? We totally remember these videos, but I, yeah, never knew what happened to all the money that they raised. Well, some of it helped pay for the development of this new drug. And that brings us to the drug's first big test. So Josh and Justin, you know, they'd managed to fund this study. It had 137 people in it with ALS. And they had pretty much staked their company's future on this study.

I mean, this was the culmination. A lot of pressure. Oh, a huge. pressure. You know, the future was at stake here. And they told me what it was like to be like waiting and waiting to hear what the results were. We were right in this office, pretty late at night. We were incredibly nervous, you know, waiting for these results. But when the, you know, the statisticians ultimately called and when the statisticians called, you could hear their whole firm cheering in the background. And so we knew before they said, you know, the numbers that, you know,

something good had happened. Wow. I mean, yeah, when the the data goes in the direction you want, that is a good, good feeling. Yes, it is. And this study eventually got published in the New England Journal of Medicine. It found that people who got the drug lived a little bit longer and seemed to function better than people who didn't get the drug. That was amazing. But it was still a small study that left some questions unanswered. Usually, if you want to get a drug approved by the FDA, you would need a second study that found the same thing. But Josh and Justin's company, that's Amalix, they decided to seek FDA approval. based on the one small study.

So fast forward to March 2022, the FDA had assembled an advisory committee of outside experts to assess this drug. And at a public meeting, those advisors sounded pretty skeptical about the study, which was called Centaur. There are many features of Centaur that limit its persuasiveness. The applicant hasn't provided robust evidence. The data isn't as strong as we would hope. Did not meet the threshold of problematic study?

doesn't establish that this drug is effective in the treatment of ALS. That sounds like a hard nope to me from this advisory committee. And it was. The committee voted 6 to 4 against approval. After that happened, a lot of people, including me, assumed that Amalix would have to wait a couple of years until it had the results of this much larger trial, which was already underway. But a couple of things happened. One of them was that people with ALS and their families, they started to write protesting this decision. So I talked to Neil Thacker of the ALS Association about it. There were thousands of emails that went to the commissioner's office.

There were over 1,100 comments that went to the advisory committee themselves. And also there was a sustained effort from ALS clinical and scientific leaders. Wow. What did these thousands of messages? say. I mean, I read a bunch of them, and the summary might be along the lines of, look, we're desperate, we're dying, and we think the FDA should give us access to any drug that might help us. And, you know, that message seemed to make a difference because in September, the FDA reconvened its advisory committee and asked them to reconsider the drug. That's really

unusual. And at this second public meeting, an FDA official asked the committee to think about the consequences of not approving the drug. So in other words, all these people with a fatal disease who are hoping the drug will help them to live a few months longer. At the end of the meeting, the committee voted seven to two for approval. And a few weeks later, the FDA approved relivrio. That's a real about face, John. The process of drug approval, I mean, how unusual is it for it to go down this way? Well, it's not unheard of to approve a drug for terminally ill patients, even if the evidence isn't quite as strong as you might like. But drugs still have to meet a standard of what's called substantial evidence that, you know, that they actually work. That's the key.

And that's sort of the lingering question here is whether this new ALS drug meets that standard. Absolutely. And how much will this new drug cost? The company says taking the drug for a year will cost about $158,000. Whoa. That's a lot of money. It is a lot of money. but it's actually slightly less than the cost of one of the existing drugs for ALS, and it is likely that insurance companies are going to pay for this drug. And are there any potential downsides of this drug being approved the way it was? Some people think there are. You don't want to have people taking a drug that doesn't work, right?

I mean, that can be harmful. Also, this approval raises some real questions about what standards the FDA is going to apply to other drugs. I talked about that with Holly Fernandez Lynch, who teaches medical ethics and law at the University of Pennsylvania. She told me she's worried about whether this decision will change the behavior of pharmaceutical companies. The message that is related to companies is you don't actually have to prove your drug works. You have to do the bare minimum to show that maybe it might work. And there's another thing. This drug, Relivrio, it'll be on the market already when the definitive study of its effectiveness arrives in a year.

too. Right. You know, if that study confirms the result of the smaller study, everybody's happy. It's great. If it doesn't, you could have this weird scenario where an approved drug has been shown to be ineffective. Yeah. I mean, what would happen then? Would the FDA, like, pull the drug from the market? Not clear, but Justin and Josh have promised that Amalix would voluntarily pull the drug if it turns out not to work. Thing is, that could be tricky because Josh and Justin own just a small fraction of this company that they, founded. Most of it is owned by investors and they put a lot of money into developing this drug and they may not want to stop selling it. That is tricky. You know, the intersection of science and business, but I appreciate you bringing the nuance to all of this and explaining even how this drug came to be. This episode was produced by Thomas Liu. It was edited by Gabriel Spitzer and fact checked by Margaret Serino. The audio engineer for this episode was Gilly Moon. Our senior supervising editor is Giselle Grayson. Beth Donovan is our senior director of programming and Anya Grunman is our senior vice president of programming.

I'm Emily Kwong. Thanks for listening to Shorewave, the Daily Science podcast from NPR.