The Current - Meet suzetrigine, the new non-opioid painkiller promising relief without risk of addiction

Episode Date: June 13, 2025

When it comes to treating chronic pain, doctors have few options to reach for aside from opioid prescriptions for their patients. A non-opioid medication recently approved by the U.S. Food and Drug Administration stands to change that. A journalist explains how researchers discovered a new way to combat pain with this drug, which a Canadian doctor describes as “almost the holy grail.”

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the more urgent in the face of the opioid crisis. More than 50,000 people have died from opioids in Canada since 2016. Earlier this year, the US Food and Drug Administration approved the first non-opioid painkiller in over 20 years. This new medication is called Suzetrogin. It is being billed by researchers as non-addictive and experts say the drug could be a game changer for pain treatment. Rivka Gulchin is a staff writer at The New Yorker, recently wrote a story called The Radical Development

of an Entirely New Painkiller. Rivka, good morning. Good morning. We will tell the story in just a moment of the discovery of this drug. It is a long path, but just explain what it is. What is Suzetrogen? Besides hard to pronounce.

Easier to say yeah for you than me. On some level, if I was gonna make an over simple analogy, which is always very helpful with these things, something like Vicodin gets in your brain to receive the phone call about pain and something like Suzetrogen or the approach of this which blocks sodium channels, which is sort of a meaningless phrase if you're not a scientist, it just doesn't let the call be placed in the beginning. So the pain

call just isn't made. I said that the path to get to this point where you would write this story is a long and complicated one. And I mean, the hunt for this drug is like a mystery novel. Tell me about this geneticist in Yorkshire in the 1990s and what this person found that was critical to the development of this drug. This is such an interesting story. There was basically a pediatric neurologist geneticist, not someone setting pain really, who came across this small population of people in an area of Pakistan where he met not just one, but ultimately a few people who just don't feel pain. They came to his attention

because there was a young man who was kind of a street performer. He would walk on hot coals. He put a knife through his arm And then he'd go to the hospital and they'd fix him up as best as they could. And the doctors came to realize that he wasn't just saying he didn't feel pain. He truly didn't feel pain. So that was like the beginning of this question. It wasn't just this one kid. It was very rare, but there were other people who had the same thing. It seemed like it was probably genetic. It began this sort of long pathway of identifying, well, what is the genetic abnormality in these kids? And meanwhile, across the world, there was Steve Waxman at Yale who encountered a population of people in Alabama who had kind of the opposite problem.

This is the man on fire syndrome. This is the man on fire syndrome. So we had one geneticist studying people who didn't feel pain at all and then another group, another researcher studying people who felt pain even when they were just like it was a kind of hot day or they touched the slide, those two lines kind of converge to start letting people know exactly how these pain signals were sensed. Because when they go wrong, you get a picture, you find out where they're going wrong, you start to solve, at least make some headway on a mystery. When you have knowledge of those genetic mutations, what does that mean when you're trying to

develop a painkiller? When you're trying to develop a pain killer? When you understand that there is a population that feels no pain and a population that feels, as you said, kind of pain in all sorts of unusual circumstances. Basically, they started looking closer and closer and saw that certain defects that affected basically what are called sodium channels channels but that kind of control the electrical signals by which we telephone the brain and tell our brain that we're in pain were defective in some way, in a different way in the different populations. One population, it was defective in a way that no calls were being placed and one population was defective

in a way where tons of calls were being placed all the time, sort of too often and too easily. So then you think, okay, well, what if I can go in and affect this spot in a quote unquote normal person? Maybe I can turn off the pain for a period of time. Why is that so difficult? It's like a target. Yeah, I mean, and so to find that target, to hit that target and be able to create that interruption,

what were the challenges in getting there? Because again, there's this initial breakthrough, but how do you go about following that up? Yeah, I mean, that's what it's so wonderful to get to speak to these researchers, one, because they have just tremendous patience and two, they sort of have stamina. So first you have to kind of identify exactly what it is that seems to be distinctive in these two populations, which is actually quite difficult. I mean, now we send off a swab from our cheek and get a kind of read out of all of our DNA, but they were not working in that time period. So that alone was a huge step.

Then they have to say, okay, we've identified this part that's weird, what does it make? And so then they have to figure out, oh, it turns out it makes these sodium channels in these peripheral nerves. So that's a huge step. And then you have to sort of think, well, what kind of molecule can interfere with that sodium channel? And I mean, the world's full of, you know, tens of thousands of hundreds of thousands of possible things that might do that. And there's some educated guesses you can make, some alleys that seem more promising than others, but it's a pretty long road. And the belief was that if you were able to do that, if you were able to interrupt that pain call, that signal,

that this might not be as addictive as doing that through opioids? Well, exactly, because addiction is something in our brain. It's our brain saying, I need more, I want more, send me more. This isn't happening there. It's just sort of not even in the neighborhood where addiction gets formed. That is quite wonderful. Just like something like Tylenol or aspirin, these aren't addictive medications. They don't go to your brain. They affect inflammatory pathways outside of your brain that are part of letting you know you've been injured or damaged in some way.

Why is it so difficult to figure out how well a painkiller works? This is something that you explore in this piece as well. The work that has to be done to try to establish whether the painkiller is doing what it's meant to do, to measure somebody's pain but also understand how that pain can be reduced. Yeah, no, that is such a good question. And it was something I hadn't really even thought about, but then became quite clear as this kind of special kind of problem because if you're studying a medication that lowers blood pressure, you know, the number, you've got a very specific

number on blood pressure. It's 150 over 90 and now it's 120 over 80. How do you give a number to your pain? You know, these sort of one to 10 scales or pictures of smiling or grimacing faces, these are pretty, they're pretty fuzzy. You know, it's kind of like when a kid gets hurt and they really want their parent to know how they feel, you know, it's all, it's kind of guesswork. So it's as if you have just like a very blurry picture of when things are getting better or worse.

It's fuzzy. So they're stuck working with a very fuzzy outcome. You're right that it's like trying to understand somebody else's dream. Yes, exactly. Meaning it's never gonna happen. But you can give a few hints, a few pointers. One of the other things that you write about

in this piece is that, and I think those of us who were in pain would find this surprising, but this idea that pain has purpose, right? Yeah, you know, it was quite moving. The researcher, Jeff Woods, who encountered the street performing boy who didn't feel pain, you know, that's a sort of Oliver Sacks kind of interesting mystery, you know.

Then there was this terrible tragedy where the boy, You know, that's the sort of Oliver Sacks kind of interesting mystery, you know, then there was this terrible tragedy where the boy, you know, because he was like a, you know, a young teenager, thought, okay, it's my birthday, I'm going to show up for my friends, I'm going to jump off the roof of the house, because you know, it's not going to hurt me. And he ended up dying from that. And Woods identified that as the moment where he realized something that, you know, later he thought, well, of course, but pain tells us, helps us not hurt ourselves, helps us notice that we accidentally touched a burning hot pan that we didn't mean to touch, helps us not do activities that we wouldn't do because we're pain averse and that people who have this extreme syndrome where they don't feel pain

Have to take all sorts of precautions to basically they're not accidentally, you know Kill themselves through sort of just you know impulsive stunts or not noticing that their hand is in boiling water The researchers say that they're not trying to the pain isn't the enemy. They're not trying to end pain. They're trying to end suffering Yeah, absolutely. It's kind of like, you know, you go to the dentist, it's great to not feel pain for the 30 minutes while you have the procedure, but then you want it back so that you notice if you bite your tongue and you sort of need it. And that's with all of our pain medications, they're time- and their intensity is limited. So that's actually a blessing and it's hard to almost think of it that way that you want effectiveness but you kind of want to cap on your effectiveness either in time or intensity so that you can

get the important messages as opposed to the messages that have lost their communicative value because you already know you have lower back pain. You know about it and now it's just too much. One thing that was interesting to me that was new to me when I researched this piece was that even opioids aren't really that good for a lot of chronic pain. I mean, you try it because you're going to try everything. For a lot of types of pain, we don't really have anything that's good, addictive or not. As I said, one of the real promises aside from the fact that the FDA approved this painkiller is that it's one of the first non-opioid painkillers or the first to be approved in over 20 years. And people see real promise in this drug.

There have been two large-scale clinical trials of Suzetrogen in the U.S. What do we know about how well it works? The clearest signal, the trial that gave us the kind of most clear information, was a post-surgical trial. Basically, all the patients could be compared very well, and they were either going to be treated with Vicodin or Percset which is a relatively mild opiate but of course,

much stronger than Tylenol or a placebo or a Suzetrogen. And it worked just as well as the opioid. It's kind of a wonderful result. It didn't have any weird side effects. Its sort of profile of side effects was slightly less than that on placebo, which of course just like a random noise in the data, but sort of funny. Now the footnote is we're already pretty good at treating that kind of pain. Vicod, bike it in and percocet or have problems, but they're relatively mild. So I guess what you want to know is, okay, post-surgical is a situation that is challenging, but not the most challenging. And we're excited to see whether this or follow-up drugs are going to be able to tackle, you know, kind of nerve pains like sciatica or

trigeminal neuralgia, which there's not great treatment for or chronic pains or the kind of complex pains from that cancer patients have where there's like a lot of factors going on. So that'll be what's really super exciting looking forward, but it's already kind of thrilling that there's just like a new mechanism, you know, because a new mechanism it's just the first step. So that's really what seems exciting to physicians, to ordinary people, to all of us. This is important because as you write in the piece, I mean, sending somebody home with opioids is like, in your words, sending them home with a gun. We know how we know the carnage that the opioid crisis has caused. What, as

you understand it, what could this drug mean for the prescribing of opioids? It is sort of the like most pressing and kind of exciting in a positive way dealing with kind of a nightmare that everyone's been going through with opioids. One pain researcher put it this way is like, it's not, we don, we don't yet have... Suzetrogen is not going to get rid of the need for some of these stronger opioids for people in a lot of pain, such as cancer patients with different pain syndromes. However, it's going to mean that when you're going on the step ladder, trying one more pain drug after another, or sometimes they have synergy trying two together, you just kind of got

another rung in there before you have to go, or you might choose to go to opioids. You just added like another step to keep you from going there too quickly. Just last question before I let you go. I mean, in writing this piece, what to you is, it's an incredible story to get to this place and the case studies that you read along the way are fascinating, but what to you is most interesting about this? I love getting to speak to scientists who are in,

on some level they're like speaking this language from some sort of small island in the Pacific that hasn't been visited very often. And it's just so wonderful to get to talk to them because they are so much more in touch with how thrilling it is to know more about how these pain signals are working in nerves and how thrilling it is to know more about where these different kinds of sodium channels are in the body and what they're doing. And that's what I found the most thrilling was to kind of go visit this kind of island of people who kind of know all these wondrous things that are not in our common vocabulary. Rufka, thank you very much for this.

Thanks so much for having me. Rufka Galchin is a staff writer at The New Yorker. At Desjardins Insurance, we know that when you own a cleaning company, things need to be tidy and organized at every step. That's why our agents go the extra mile to understand your business and provide tailored solutions for all its unique needs. You put your heart into your company, so we put our heart into making sure it's protected. Get insurance that's really big on care.

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what the development of this painkiller might mean for Canadians and what other non-opioid options would be available and might be being developed. Dr. Hans Clark is here to answer those questions. He's president of the Canadian Pain Society, medical director of the Pain Research Unit at Toronto General Hospital. Dr. Good morning to you. Morning, Matt. Always a pleasure. Good to have you here. What did you think when you first heard that the FDA had approved this drug? Well, I can tell you that on the day they approved it, I started to get emails from patients all over

the country. Immediately. Immediately. When am I going to get this? When is it going to be in Canada? And how can you prescribe it for me? How much of a breakthrough is Suzette Dujene? The jury's still out.

It's going to start to be given to the population and we're going to see how it rolls out over the next several years. But I think Rivka hit it on the head in saying we now have a new tool. And this new tool is going to be helpful in that armamentarium for patients who have pain. And so we know from a potency perspective, if you look at the data very granularly, it's probably as good as a non-steroidal anti-inflammatory, maybe as she said, a Percocet, so to speak. So there is another medication that we can trial for things like, for example, diabetic neuropathy. So there are so many patients. The best drug we have right now is a drug called pregabalin. And now we have a tool that perhaps dampens this. What's pain? It's a

nervous system signal. Well, that's the thing. As you understand it, how does this work? Yeah. And so, you see the comments about the system that, you know, drives from the periphery into the spinal cord up to the brain, and you have a drug now that targets that peripheral aspect, so that signal that gets to the spinal cord without the cognitive aspect. So if you build on what Rivka's saying, that that's the reason the addiction potential is so low. It's almost the Holy Grail. It's you have this peripheral blockage without affecting the central brain component. And that's the reason it's exciting. That's really strong language, almost the Holy Grail.

Almost. What does it tell us, and the process of developing this drug, which went over decades, what does it tell us about the nature of pain and what we know about pain? So many things, Matt. So this is not new. If you go back two decades, you mentioned it, we're two and a half decades into any drug being approved because of our Oxycontin

story. And this sodium channel story was tried two decades ago. And guess what they figured out that you have cardiac issues with sodium channels. Sodium channels are everywhere in our body. And so how do you actually find the voltage-gated channel that only blocks the periphery and doesn't affect these other organs? And I've seen some of this data kind of at that pre-clinical animal level and always thought, hey, if they can get it to where we are now, we got a shot here at a drug that certainly can have huge impact. When those patients of yours emailed and called and said, when can I get my hands on this? We got a shot here at a drug that certainly can have huge impact when those Patients of yours emailed and called and said when can I get my hands on this? What did you tell them? We got a statement from vertex the company that makes this drug

They have yet to submit it for approval to Health Canada But they said that they are in their words evaluating potential opportunities for geographic expansion beyond the United States And so great point. I even had a conversation with some of the folks at Vertex and said, hey, I'm a president of Canadian Pain Society. I want this drug in the Canadian population. You want the tool. Oh, absolutely we want the tool.

But you know, it's a business and these industries are businesses. And so, our population is 8 million of our 37 million. The American population is 370 million. That means 75 million. The American population is 370 million, so that means 75 million. The European population is about 150 million. There's more money elsewhere than here. Right. But they owe it to the Canadian population to bring this... And I'll be honest with you, Matt, Health Canada, this is an opportunity that they would welcome. They would potentially

even say, hey, we have an opioid crisis. This opioid crisis has been the bane of our existence for a decade, and we're in a worse position than we've been 10 years ago. So hey guys, come talk to us. Let's figure out how we can bring this novel tool to our Canadian population. How long do you think it'll be until you get your hands on that tool? It's going to come down to the company and Vertex and whether they actually see the value. And I don't know Matt, maybe they're waiting for those other phase three chronic pain trials because we know that that's

going to be a big, I think the bigger population is the chronic pain side of this. But my hope is that they actually just reach out to Health Canada and start talking about these issues and start saying, hey, what does it mean to you and this country to help us get this into the population? And if they can do that, it could happen sooner rather than later because there are metrics in the background to get this moving.

One of the interesting things, obviously, about this is that it is sensibly non-addictive, that it does not have the collateral damage, if we can put it that way, of the opioids that are used. How are opioids used now in terms of treating pain, given everything that we know? We've been at this for a decade. We've tried harm reduction strategies. We've tried handing out needles, doing all these things.

We are in a worse position. We tried reducing our opioid prescribing. We're in a worse position today than we were a decade ago. And now it's time to realize that, you know, the pain part of this game is super important. And if we can tackle and build systems earlier, we won't continue down the path we're on. So now we have a new tool.

And the beauty of this new tool and where opioids are gonna be used, they're gonna always be needed, Matt. They're not disappearing. We're gonna need them in the acute pain setting. We're gonna need them when you break your femur. I've heard things like, we have non-opioid emergency departments.

It's blowing my mind that these concepts are even out there. Or that we're never going to prescribe an opioid, but we're a pain clinic. How is this even, how have we landed here? Because these are the drugs that actually will address people's pain. There are side effects and there's an addiction component to this, but these are the drugs that we need right now. The current drugs we have here that are coming are great. An opioid in the acute pain, severe trauma setting,

absolutely necessary. In the palliative patient with cancer, absolutely necessary. Where it may not be necessary and has caused us a lot of problem is this chronic non-cancer pain area, which encompasses so many patients. Given everything that we know about opioids, how easy is it for people who legitimately need them to

address their pain? How easy is it for them to access them? Oh it's a disaster right now Matt. You know what first of all we don't have primary care. Secondly a lot of what's happened is we've scared physicians away from treating pain and you know it's now how do we refer to a tertiary care center or a specialist like myself or others? And one in 170,000 Canadians have access to this type of care. So we need to build models and embed as we talk, you know, the mental health part of this, the physical health, the chronic pain treatment aspects earlier in the pathway as opposed to, you know, waiting a year and a half when you have a condition to see a specialist.

What sort of research is happening here in this country now when it comes to non-opioid painkillers? I think we're at one of the most exciting times, Matt, right? So I'm sitting as the president of this society with all of this reinvigorated interest into this space. And so we have, you know, NAV potential, uh,

formulations, we have endocannabinoids that we're talking about potentially coming down the DIN pathway with various companies. What does that mean? The endocannabinoids coming down the DIN pathway? You know, and so we have way more endocannabinoid receptors than opioid receptors in our body. The Runners-High we always thought was an endogenous opioid, it's actually an endogenous endocannabinoid system. So there are, and that's just a couple of molecules that we're thinking about bringing down this pathway. And any non-opioid molecule will be a game changer

for where we're at. We haven't had a new medication in this space, as we know, for 2.5 decades. And so you bring it and we can use it. It's a new tool and we will use it. Are there treatments beyond painkillers that work to treat pain? We know that they're the triad, right? What is the triad? What I can do for you, what medication I can give to you,

what injection potentially I can do for you. We're not sure how great these injections actually are long-term. Then it's what your brain can do. It's a nervous system signal. So the mindfulness, hypnosis, yoga, exercise in particular, and what that does to your body. You either can use your body to help yourself, your brain to help yourself, or medications. And those who figure out the pieces of the puzzle that are fit together are the ones who can live with this chronic disability long term. And I agree with Rivka, the painometer and these numbers are ridiculous. But it's what you need to change to get approval by these regulatory bodies.

And that's why these numbers still stick around. But patients will tell you, my number doesn't change, but my life can change or my, you know, what I do can change. And that's the meaning and that's the meaningful outcomes that we need in the pain space. I guess just the last point on this. It's interesting her saying that one of the things that she loved about doing this research is talking to people who they're learning new things about this.

I mean, this is your life's work in many ways in looking at pain. What to you is most tantalizing about a discovery like this? Think about this, Matt. Pain has only become a disease in 2021. Up until 2021, pain has been a symptom of conditions. And the World Health Organization declared it a disease. That means we as a country need to also put it in that position and fund it in that

position. It's still the number one driver of disability in our country. We spend $40 billion a year in lost revenues on chronic pain. And so if you want to actually move this and move this forward and save the economy and reshift things and improve our healthcare and the quality of life Canadians, pain needs to be a priority in this country. Dr. It's good to see you again. Thank you very much. Always great, Matt. Dr. Hans Clark is the president

of the Canadian Pain Society and the medical director of the Pain Research Unit at Toronto General Hospital. You've been listening to The Current Podcast. My name is Matt Galloway. Thanks for listening. I'll talk to you soon. For more CBC podcasts, go to cbc.ca slash podcasts.