The Journal. - Trillion Dollar Shot, Episode 1: Birth of a Blockbuster

Episode Date: May 13, 2024

Before Ozempic, Wegovy, Mounjaro and Zepbound, there was Lotte Bjerre Knudsen. In the 1990s, the young scientist at the Danish drug company Novo Nordisk was trying to unlock the key to a new technology for treating Type 2 diabetes. To her bosses, Lotte’s project, which focused on a hormone called GLP-1, looked like a distraction.  But as Lotte fought to save her diabetes project from the chopping block, she couldn’t have imagined how much of an impact her breakthrough would have. Her work would pave the way for a hit drug called Ozempic. And it would unleash a new class of blockbuster drugs, pitting two companies in a race to become the world’s first trillion-dollar pharmaceutical company by market cap. Listen to Part 1 of “Trillion Dollar Shot” now. Learn more about your ad choices. Visit megaphone.fm/adchoices

I admit to a slight bit of syringe anxiety. I'm not happy to admit that, but that is something that I've dealt with. Back in January, I hopped on a video call with my colleague Bradley Olson, who's out in San Francisco. Brad was about to give himself a dose of a drug he'd been taking for weight loss. It was an unusual and personal moment for a co-worker to share. Whenever I would get it, like the first couple times, I would like just breathe in, breathe out, you know. And then it would feel like ridiculous because it's like a very small pinprick that you barely feel, you know?

Brad has struggled with his weight for more than 20 years. And he said this medication made it easier than it had ever been for him to lose weight. In five months, Brad had lost about 40 pounds. You know, the thing that was in the beginning like a revelation, I know that sounds crazy, but like without medicine, when I would eat well, when I would

kind of follow a good course, I would just feel very hungry and it wouldn't be a good hungry. It would just be annoying. Annoying and disruptive and frustrating. When you're on the medicine, it was just great. Those voices, which I came to really hate, were just silent. This medicine is part of a new class of pharmaceuticals that has exploded in popularity over the last few years. The most well-known is Ozempic. Brad was taking one called Manjaro.

Anyway, so I'm going to take my syringe out of the box. It's five milligrams. And, you know, it's refrigerated, so it feels vaguely cold. You can put the injection in your upper thigh or in your, like, belly or stomach. I have

never done the belly, just because I don't want a syringe in my belly. And so the thigh was always kind of where I put it. That day, that dose, was Brad's last shot. He had decided to stop taking the medication. So without further ado, here we go. Here's the last hurrah of Brad's time with Manjaro.

All right, there we go. Here's the last hurrah of Brad's time with Manjaro. All right, there we go. How do you feel, Brad? It's done. I think I feel good. I feel a little bit of anxiety. Yeah. Because when you're on the medicine, it's so easy to lose weight that you don't really have to use any willpower or plan or anything. It just is going to happen and you know it's going to happen. Brad documented his journey on and off the medication because his time on the medicine and his decision to stop taking it stirred up a lot of feelings. Surprise,

anger, uncertainty. It was a lot. So after Brad took his last shot, he and I decided to report on the impact of these drugs. We set out to understand, are they a true turning point for America's struggle with obesity? And if so, are we ready for everything that would mean? Because people who've taken these medications told us the same things over and over again. All of a sudden, just the weight starts falling off. You know, eight pounds the first month. I felt like it was a miracle. Three pounds the second month. Life-changing for sure.

Ten pounds the third month. That's how powerful this medication is. Then it just was like, how is this happening? I could tell it was working. And I could tell that it was changing my relationship with food. And I liked that. This type of success has meant huge windfalls for drug makers. We said, oh, Jesus, this can become a big, big drug. It's been a boon.

There's no denying that. You know, the demand is higher than what we can deliver to people today. And that demand for these drugs is reverberating across society. And I thought, well, I'll stay on this for life because it's so helpful. And then I realized what it was going to cost me. They're just bank breakers. Okay, if I can't get the drug, what can I take instead? What's close? There are so many people even selling bathtub Ozempic.

There was a lot of excitement. There was a lot of skepticism. And I can imagine a future where life expectancies are actually increasing because of this class of drugs. Whether you think these drugs are a miracle or you're skeptical of what they promise, they're changing how we approach one of the most intractable issues in our society, obesity. And it's just the beginning. From the Journal, this is Trillion Dollar Shot.

I'm Jessica Mendoza. And I'm Bradley Olson. This is Episode One, Birth of a blockbuster. Attention all soccer fans. From Orlando to Los Angeles, take to the fields of the USA for your next vacation. Ready to kick off? Discover exciting games and events.

Plus, find amazing hidden gems in cities full of adventures, delicious food, and diverse cultures. You'll love it so much, you'll want to extend your stay beyond the matches. Get the ball rolling on your soccer getaway. Head to visittheusa.com. Summer's here, and you can now get almost anything you need delivered with Uber Eats. What do we mean by almost? You can't get a well-groomed lawn delivered, So why did you want to lose weight? I'm trying to be as honest as I can as I think about it.

It's a hard question. Yeah. And I wanted to look better, you know? I know that some people will say, it was for my kids, and it was, I wish that I had some noble reason. I'm just being honest, you know. The noble reason is like, I've got kids and I want to run with them.

And I would think about that, but I would run with them. And I would think about other things. But in the end, I felt like I'm not supposed to be like this. You know? This isn't me. Brad's story is familiar to millions of Americans. For decades, obesity has been on the rise. The CDC says one in three adults in the U.S. is obese.

The condition is linked to shorter life expectancy, to diabetes, heart disease, and to some cancers, not to mention larger health care bills. And billions have been poured into addressing the issue. But nothing's been able to bring the numbers down. What most doctors recommend, diet and exercise, they don't work long-term for most people. And short of surgery, the great minds of industry, technology, and medicine just haven't been able to find an effective treatment until this new class of drugs. Every doctor interaction that you have when it's about weight loss is always the doctor's like, I'm telling you things that you're not going to do. They don't say that, but it's just the subtext is basically like this conversation of,

I'm telling you things to do, and I don't think you're going to do them. It was like we were performing in a play. He was pretending to be a doctor that believed he was giving good advice, and I was pretending to be a patient that was listening and was really going to make a change. Neither was true. And the difference with this conversation was like, this is going to work. There was no doubt about whether or not it was going to work. And that was such a difference. And how did it go? Like, how quickly did you start to lose weight? And what were your reactions? I was just shocked. I had heard people talk about being on the medicine and how it really zapped their cravings. You know, I had read that. But to experience it is another thing entirely.

it is another thing entirely. Brad's going to share more of his own story throughout this series. But first, we want to go back to where it all started. Ozempic was developed by a Danish pharmaceutical company called Novo Nordisk. The story starts in the 1990s, with a woman named Lotte Bjerre Knudsen. I did a lot of work in the laboratory. I was the lab rat. Lada was a young scientist at Novo Nordisk.

When she was just starting her career, she was focused on what most scientists at Novo were there to do, develop drugs for treating diabetes. I always wanted to work for this company, and I was very set on wanting to make product-related research. I never wanted to be an academic researcher. I just knew that I wanted to make products that could somehow be useful for human beings. And Lara had a bit of a reputation. I won't say that I have a temper. Maybe some people would say that

about me, but I'm very dedicated and energy. I had ideas. I wasn't really shy and I did not give up too easily. And so what was it that you were working on? We had all kinds of ideas, you know. At that point in time in pharma for diabetes, there was a big desire to do something new, you know. And then GLP-1 was just one of those ideas that were around in the community at that time. GLP-1. It stands for glucagon-like peptide. It's a gut hormone, and it's the basis for this new class of drugs. When Lada started working on it, there was research that showed that the GLP-1 hormone lowered blood sugar levels, which is important for treating diabetes. But no one had figured out how to make GLP-1 work as an effective treatment. It didn't hold up in the human body for long. It was gone in two minutes.

That was really the problem to be solved was to make GLP-1 long-acting. So when you say gone in two minutes or making it long-acting, does that mean it like breaks down in the body as soon as it like appears? Yeah, there are several ways that things can disappear from the body, right? One is that metabolic enzymes can degrade it, but then also things can be taken out via the kidneys. Lotto worked with a team to try to solve this puzzle, to try to get this powerful hormone to stay in the body long enough to work. But then she went on maternity

leave. And when she came back in 1994, Novo had gone through some restructuring. Most of the people I'd worked with, they were gone. So I was kind of like the only one that knew anything about those projects. And the new leadership said to me, you know, you are the one that kind of knows this biology, so you figure out what we should do. What did you do? Did you freak out? Not so that anyone could see it, right? But it was a little bit of a lonely time, right? Because the people that I considered my closest work friends, they were gone, right? So I still had a group of laboratory technicians that

were working with me and doing cool things in a lab. But this thing about figuring out how to lead the project, which idea to focus on, I was completely alone with that. So I was basically sitting in my office for a couple of months, kind of staring at the walls. in my office for a couple of months, kind of staring at the walls. Lada was now leading the GLP-1 team. But they weren't making much headway towards a functional drug. And leaders at Novo started to get antsy. Leaders like this guy.

Yeah, my name is Lars-Rabin Sorensen. I used to be the CEO of Novo Nordisk. GLP-1 research was not the company's priority. So Lars was like, why were they even messing around with this hormone? Well, I have to admit at that time, I thought it was a strange idea. We were primarily selling insulin. Right. And competition in the area of insulins were quite fierce.

This GLP-1 compound was very, very short-lived. Right. And really, it was difficult to create a drug out of it. Quite frankly, I was worried that we were spreading our resources too thinly. We were a small company, so I knew everybody. And they would come into my office and, you know, ask for more resources. I asked Lars if Lotte was one of those people. Oh, yeah, all the time.

I could not meet Lotte without her really getting on my case to prioritize her projects better. Lotte Knudsen is a person that's very, very difficult to say no to. Even with Lotte pushing the project, Lars considered canning the whole thing. I do recall that we did give him 12 months to say, you got to come up with something which is more convincing.

And my recollection is it was extraordinarily slow developing at the time. And I'm sure a lot of people will say this is because we had no resources. But anyway, because of their stubbornness and their skills and their professionalism, they eventually were able to create a molecule that was protracted so it became a real drug that we could start to make clinical trials on. Lada and her team had met the deadline. By then, it was 1997. All told, it had taken about four years for them to create a compound that mimicked the effects of GLP-1

and didn't immediately break down in the body. They called this compound liraglutide, and it stayed in the body for 24 hours. Think of it as a precursor to ozempic. Same scientific idea, just not as powerful. The next step was to test liraglutide on patients. But inside Novo Nordisk, Lada's team still had to fight for limited resources. And that problem felt to Lada's boss. As a very young lad, I had big hair, big curly hair, lots of hair, not anymore. And so I looked like a typical young nerdy scientist. That's Mads Krogsgaard-Thompson, a former senior vice president at the company

and a big champion of Lottes. And he wasn't afraid to get creative to keep her project going. Well, the first stumbling block was that we were a little bit behind in production capacity for insulin. So we literally had no utilization of any production facility in the company.

So I had to give the team money to go to Belgium to ask another functional company to produce it for us. And so you had to do it basically off-campus to get this stuff done? In a competing company already. In a competing company. Another company. Eventually, they did get enough medicine for human trials.

But at first, it produced a really nasty side effect. The people in the phase one trial, they vomited. Wow. So they literally felt sick. And this, of course, didn't convince management that this was very exciting at all. Right. They were like, this, I don't know what you guys are doing over there, but it doesn't seem to be working.

No. So there was actually a feeling of, OK, is this the end stage for this GLP-1 project? And then there was a concern about cancer. We saw tumors in rats and mice up here in the thyroid gland. And suddenly these tumors seemed to be happening dose-dependently over time in rodents. Luckily, we didn't see them in rabbits, we didn't see them in dogs, we didn't see them in monkeys. But the regulators, FDA and so on,

were not happy with seeing tumors in two species. The team did more testing, and ultimately, they concluded that the tumors they saw in rodents were not relevant in humans. But it would take years before the FDA was satisfied that Novo's loraglitide was safe for people. And Novo Nordisk still advises against taking GLP-1 drugs if you have a history of thyroid cancer.

So the FDA approved loraglitide in 2010. Do you remember the moment you heard about it? My wife and kids had gone to bed, and then I actually, I get a phone call at like 11.30 in the evening. Mads, we've got it. We've got an approval. And you know, you just shout out loud. I just got extremely excited, so much that my family woke up and was really annoyed with me. They're like, why are you so excited? It's the middle of the night.

Yeah, yeah. I had to apologize. So I took a good McGowan whiskey, took a good shot of that and celebrated over the phone with the colleagues. Yes, I was in my bed. But the minute I saw the number on my phone, I knew we got this. I felt a great sense of accomplishment. It was more than 10 years in the making.

And if we hadn't gotten that U.S. approval, maybe it would have been just not going anywhere. That would have been a great shame for the people who need this kind of medicine. Liraglutide went on sale under the brand name Victoza. It was approved to treat type 2 diabetes, and it was a modest success. More importantly, though, it was a proof of concept. Lada's GLP-1 research had led to an effective drug. And the next drug, a new invention building off loraglitide, was already in the

pipeline. It would be a blockbuster, one that would turn Novo Nordisk into a company that was known for more than diabetes. Because here's the thing, since almost the beginning of Lotta's research, she knew that GLP-1 had another effect. Weight loss. Did that surprise you, that it was weight loss really that made these drugs kind of soar to the top and make it kind of a household name at this point? Yes and no, because I remember I've heard it for such a long time. Ever since back to the early 2000s, when I was first lucky enough to be able to actually hear from some patients, they had tears in their eyes.

They said, you know, I've been hungry for 20 years. Now I can manage to have a normal life. So, how did a diabetes drug turn into a weight loss phenomenon? That's after the break. Introducing TD Insurance for Business, with customized coverage options for your business. Because at TD Insurance, we understand that your business is unique, so your business insurance should be too.

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The factory there is a hive of activity. All right, just keep an eye out. Now we're in the area with a little bit more robot traffic. On an assembly line, a machine places vials of clear liquid into blue syringes. You can see the pens clattering out. What's on the line there? Uh, semaglutide. Semaglutide.

Or... Semaglutide. Semaglutide. Semaglutide. Semaglutide. Semaglutide. We've been saying semaglutide. Is that right? That is so correct. Okay, because we hear, like, semaglutide. Semaglutide. We've been saying semaglutide. Is that right? That is so correct.

Okay, because we hear like semaglutide or... So that's incorrect. It is. It's semaglutide. For the record. Thank you. However you say it, semaglutide is Novo's successor to liraglutide. It came with some side effects. Nausea, vomiting, gastrointestinal issues. But semaglutide is a more effective GLP-1 compound,

and you only need to take it once a week instead of once a day. It's also the key ingredient in Ozempic. In 2017, the FDA approved Ozempic specifically to treat type 2 diabetes. That year, Novo Nordisk geared up for a big U.S. campaign. Did people inside Novo realize they had a hit or a blockbuster in Ozempic around the time of the launch? So there was a lot of excitement and preparation. We thought this could be one of the most important products that the company had brought to market to date.

That's Dave Moore. He was in charge of sales and marketing when Ozempic launched in the U.S. in 2018. With a possible hit on their hands, Dave says the company started to get the word out. They promoted the drug's ability to lower blood sugar levels to specialists and doctors. And they spent a lot of money

on branding and marketing. But you probably know that already because of this catchy tune. Oh! Oh! Oh! Ozempic! People with type 2 diabetes

are excited about the potential of once-weekly Ozempic. Who came up with the idea for the jingle? We test these, and there was a really strong recall, which is important in any of these campaigns. Did you like the song? Did it resonate with you?

I did know the song, and I can actually tell you the first time I heard it, and I'll date myself, but I was roller skating back when I was in school in 75, and it was a hit, right? I don't know if you'll hear this. Oh, oh, oh, it's magic. You know. Never believe

it's not so. There you go. That's incredible. My name's David Payton. I'm the singer-songwriter with the band Pilot. And I wrote the song Magic, being used by Ozempic extensively. David Payton wrote Magic 50 years ago. He didn't think too much of the fact that it was recently picked up for a drug ad. Not even when he saw the company Novo

Nordisk on his royalty statement. David figured magic had been used many times before. When it first came out in 74, Coca-Cola got in touch with me and they, yeah, it's been used extensively for a long time. And even Selena Gomez, you might know, she had a pretty big hit with it in the States around about 2009 or thereabouts. I've heard lots of hip hop versions, which are very strange because, you know, there's a lot of rapping going on and then the chorus is used. Flo Rida did a version of Magic. But something about this version seemed to land differently. About a year after Ozempic hit the market, David was at home in Scotland when he got a call from a friend. And he phoned me up really excited and said, David, do you realize your song is on television here in the States?

And I said, it must be every 20 minutes I'm hearing your song. And I said to him, well, I knew it was being used, but I didn't realize it was that much coverage that was going on in the States. Ozempic was really starting to pick up steam. Except the hype wasn't because it was a drug for diabetes. People were talking about it for weight loss. It's known as Hollywood's worst kept secret,

as celebrities dropped noticeable amounts of weight quickly. I mean, I cannot scroll through my social media without someone mentioning the Ozempic diet. By the way, you've been working on your body and on your health? No, that's Ozempic diet. By the way, you've been working on your body and on your health. No, that's Ozempic. The topic Ozempic has over 300 million views. When I look around this room, I can't help but wonder, is Ozempic right for me? Now, companies can't promote their medicines for off-label use. But it's not unusual or necessarily unethical for doctors to prescribe a drug for something it isn't FDA approved for.

I asked Dave Moore about all this. He's the guy who led the launch of Ozempic in the U.S. As you know, today, a lot of people don't necessarily associate Ozempic with diabetes. They associate it with obesity treatment and weight loss. How did that happen? And when did people at Novo start realizing that it was being prescribed off-label for weight loss? Yeah, I'm glad you asked that question. I'll start with the first part. It's really important, and I'd love to stress to your listeners that Ozempic is for type 2 diabetes. And I would ask everyone to really think about the uses of these medicines based on what they're intended for.

The second part to your question, we knew that there was a need for new medicine for people living with obesity. And we were studying higher doses of semaglutide for chronic weight management. And that was, you know, in clinical trials while Zempik, you know, of course, was being launched into the market as a type 2 diabetes medication. I totally understand what you're saying. However, it did happen that doctors prescribed Ozempic off-label. I mean, they were making jokes about it at the Oscars. Like, what do you do in a moment like that?

I think what we have to do is play our role and do our part to ensure that we try to correct any time that happens. We, of course, are not denying that those things happen. We're not being shy. We see the media. And ultimately, clinicians make the choice, right? And our position is firm and clear. We don't want Ozempic used off-label, and we only want it to be used as it's intended. used off-label, and we only want it to be used as it's intended. As Dave mentioned, Novo was doing research into their GLP-1 drugs and weight loss. But for a long time, it wasn't the priority. Diabetes was. Because drugs to treat obesity looked like a risky proposition. Here's Lars Rabian Sorensen, the former Novo CEO. I was not against that. I actually thought it was a good idea.

However, I was a little bit cautious about expressing this publicly because at the time, almost all without exception, weight-lowering drugs have failed, some even so badly that companies were sued. So I knew that if we started talking too much about the obesity effect of GLP-1, we might taint a very good diabetes drug. There was a quote that's been circulating the internet a little bit that is attributed to you from 2005, where you say that obesity is primarily a social and cultural problem. It should be solved by means of a radical restructuring of society. There's no business for Novo Nordisk in that area. Do you remember saying that? I remember that. and I believed it at the time. Yeah. I was not aware at that time of the great difficulty, number of people with severe

overweight. I have absolutely no doubt that I said this. What ultimately changed your mind about developing GLP-1s for obesity treatment? First of all, you get in contact with these individuals that are struggling with this for their entire life. That has an enormous impact on you as an individual. Then there's also a commercial motive in this. This is a huge potential commercial market for the company. So it was composite of patient consideration, but also pursuing a

commercial opportunity for the company. So Novo Nordisk released Wegovi in 2021. A higher dose of semaglutide approved specifically for weight loss. In one major trial, patients lost an average of about 15% of their body weight in just over a year. And it wasn't just Novo. Another pharmaceutical giant, Eli Lilly,

had also been working on GLP-1s for years. And in 2022, they were hot on Novo's heels. Eli Lilly answered Novo's semaglutide with their own compound, terzepatide. Terzepatide mimics two gut hormones, GLP-1 and another one called GIP.

That made terzepatide even more effective. In the spring of 2022, Eli Lilly released Manjaro, which was approved for type 2 diabetes. I Lilly released Manjaro, which was approved for type 2 diabetes. I started taking Manjaro and I've lost 65 pounds. Last year, they came out with Zepbound for weight loss. Zepbound made by Eli Lilly, potentially more effective for losing weight than any other drug on the market. And GLP-1 medications also got a huge endorsement from one of the most trusted voices in America. For 25 years, making fun of my weight was national sport. Oprah. In my lifetime, I never

dreamed that we would be talking about medicines that are providing hope for people like me who have struggled for years with being overweight or with obesity. Suddenly, Novo Nordisk and Eli Lilly were leading a booming market. Novo is now the most valuable company in Europe. It's locked in a race with Lilly to become the first trillion-dollar pharmaceutical company by market cap. And demand for these drugs has gotten so high that Novo and Lilly cannot keep up. The FDA put semaglutide on an official shortage list in 2022.

Terzepatide followed just months later. Here's Novo's Mads Thomsen again. Did you ever dream that it could be this big, ultimately? My dream, but that was just a dream, was that one day it could be the number one drug class in the world. And right now, this year, the latest forecast is that the GLP-1 class is actually going to be the number one drug class in the world. But it's gone surprisingly fast, to the extent that neither we nor our peers at Eli Lilly can deliver enough products to satisfy the market. Thank you for calling Walgreens Pharmacy. I can help you. Where are you from? I'm from Vietnam. I help you.

China, go to the pharmacy. I can help you. Pharmacists can't stock the stuff fast enough. My colleague Brad Olson, you heard from him at the start of the episode, he and I called a bunch of pharmacies all over the country. I'm just calling to see if you have any GLP-1 drugs in stock, like Ozempic or Mount Jaro. No, we don't. No, unfortunately we do not. We haven't gotten it in the past few months.

No, it's not available. I think next month it's going to be available. Literally, like, every injection right now is so hard to get. We're out of stock on it. On all of it? Yeah. Today, there's no doubt Americans want these drugs. But almost everyone we spoke to for the series, from patients to doctors to lawmakers, pointed to the same big issue, price.

These drugs are very expensive, about $1,000 a month out of pocket in the U.S. Insurance often won't cover them for weight loss, and it's recommended that the medicine be taken for life, or else studies show people gain the weight back. My colleague Brad also ran into the affordability issue. And so you did stop taking Monjaro after about five months. Why? I would say it's mainly cost. I just can't afford, you know, that expense over the course of my

lifetime out of pocket. And so for me, starting without insurance is sort of like a choice where you know in the end that the jig is up, like you're not going to be able to keep taking it. So how long after your last dose before you started to feel the cravings come back? It was probably three weeks. Okay. It became hard because it became like you're kind of without a net. You know, in the circus, you're on the tightrope and there's no net under you. And the medicine was like having the net.

You're like, oh, I can fall off this tightrope, no big deal. That's what it feels like. Yeah. Brad decided to go without Annette. But as we reported the series, he and I talked to people who weren't so willing to give up a drug that they felt changed their lives, even if it was more than they could afford. Okay, if I can't get the drug, what can I take instead? What's close? And so they resorted to riskier measures.

What I received in the mail was a tiny vial filled with white powder. Okay. Which could, honest to God, be anything, because, like, who knows? That's next time on Trillion Dollar Shot. Thank you. Matt Kwong, with help from Jeevika Verma. Additional production from Adrienne Murray-Nielsen. This series is edited by Catherine Brewer. Fact-checking by Sophie Hurwitz. Series art by Pete Ryan. Sound design and mixing by Peter Leonard.

Music in this episode by Peter Leonard and Bobby Lord. Our theme music is by So Wiley. Remix for the series by Peter Leonard. Special thanks to Maria Byrne, Stephanie Ilgenfritz, Kate Leinbaugh, Peter Loftus,

Sarah O'Brien, Enrique Perez de la Rosa, Sarah Platt, Suna Rasmussen, Jonathan Sanders, Nathan Singapak, Lei Ying Tang, Rolf Winkler,

Liz Esley White, and Tatiana Zamis. Thanks for listening. Episode 2 drops next Sunday, May 19th.