Hello everyone, welcome to the Life Science Rundown, the podcast where we discuss current regulatory complexities facing the life science industry and explore innovative ways to overcome those challenges. I am your host, Nicholas Katkman, president and CEO of the FDA Group. Before we get started, here's a quick word about who we are. The FDA Group is a technology and consulting firm that helps life science companies in the areas of regulatory submissions, audit projects, mock inspections, staff augmentation, and remediation. So, if you ever find yourself in need, just head over to thefdagroup.com to check us out and get in touch.
So, today we are going to be talking about how can society turn the scientific promise of GLP-1 therapies into a true public health success while ensuring affordability, equitable access, trustworthy information, and responsible regulation. And I'm very excited to introduce my guest for this podcast, which is Dr. Rob Califf. Hey doctor, how are you doing today?
Hey Nicholas, I'm doing fine. Good to be with you.
Absolutely, thank you for joining. So, before we jump in to the podcast, would you kindly introduce yourself?
Sure, I'm a cardiologist by training, grew up in South Carolina. Most of my life I've been at Duke University. In fact, we had our centennial last year at the university and I realized I'd been associated with the university for more than half of its 100-year existence. But driven by the need to understand which treatments were most effective, I got very involved in clinical trials early in my career, which led to the development of an entity called the Duke Clinical Research Institute, which was mentioned for
clinical trials and outcome studies. And that led to interactions with the FDA and eventually I was asked to be commissioner of the FDA in 2016 by President Obama and then was brought back for a repeat remedial performance by President Biden in 2022. And in between my times at FDA, I worked between Duke and Alphabet, or Google as it's known, at Verily and Google Health, helping with the health and medical implications of that amazing enterprise.
Okay, excellent. Well, thank you very much. I will just notify the audience I have very bad allergies so hopefully it doesn't become too distracting but without further ado let's jump in. So, before discussing GLP-1 therapies specifically, what is the fundamental goal of public health and how should that goal shape the way we think about new medical breakthroughs?
Well, public health, you know, is a word that may seem to mean a lot of different things to different people but at least when I think about public health and my time working in government really in the midst of one of the most important public health enterprises in the history of the world really. I think the goal of public health as opposed to the goal of individual medical care is to improve the longevity and healthy longevity of the entire population including all of its segments. Whereas in the individual case, let's say a doctor-patient relationship, which is where I spent most of my career, your fiduciary responsibility is to the individual patient. The good of all is a consideration but it's not the primary consideration. And we can, as we talk about GLP-1s, it's a really good example of where those responsibilities can come into conflict and need to be resolved.
Just a little fun fact, my father was director of public health for a town in Massachusetts just outside of Boston for his entire career. And I remember one of his badges of honor was his efforts in reducing the amount of tobacco consumption. Which was very successful, as we see, right? So, I actually come from a family of public health.
Well, that's great. And I think it's, you know, I'm sitting here in Durham, North Carolina, which I love, but Duke University was built on the money made from James B. Duke, who made his money by automating the production of cigarettes for the first time. And that led to the deaths of so many people. It's been a great triumph of public health to reduce that. Although, we still have 30 million combustible tobacco users in the United States, and it's still tied with hypertension for the leading remediable cause of death. So, great work has been done, but more work yet to be done.
Absolutely. So, why do you believe GLP-1 therapies represent such an important moment in the history of obesity and chronic disease treatment?
Well, like I think almost everyone can identify with this feeling that we've had as we watched the population get larger and dealt with friends and ourselves as we gained weight, knowing that there's an unhealthy component to it, but constantly feeling like we're being admonished if we're overweight for having a moral failing. And along the way many people try to develop pharmaceutical, pharmacological therapies, and I spent a small part of my career actually working pretty hard with systematic overviews and interacting with the FDA when I was an academic to make sure that outcome studies were done because prior to the GLP-1s, almost all of the drugs that were tried for obesity had serious toxicities. Some really were the toxicities very much outweighed the benefits. So, on the one hand, here we have a behavioral component of sort of regarding as a moral failing, which didn't work very well, and then we weren't successful on the pharmacologic front. And I'll also say that many people made a lot of money writing books and selling things for diet and weight control, the net effect of which was almost nothing, really. And to me what's most amazing about the GLP-1s, and of course, I mean, as you know, but just for all the audience, when I refer to GLP-1s in this conversation, I'm really talking about a whole class of drugs that deal with what we now know are multiple pathways involved between the gut and the brain that we're just beginning to unravel and understand. What's remarkable about this to me is not only is it an effective treatment, but also the knowledge that we're gaining about the biology and the behavioral components and what's involved, I think will unlock a lot of other issues that we need to address in the care of people when it comes to nutrition, weight, diabetes, and as it turns out, many other related issues such as gambling, addictions of various types, and even use of tobacco.
Well, I heard GLP-1s actually has some benefits toward reducing the amount of alcohol consumption. I don't know if that's true, but that's what I've heard.
Well, I think when one is arguing at a refined level with neuroscientists, we can have discussions about whether we're really dealing with addiction in the classical sense, but I don't think there's any doubt that these drugs affect our propensity to get attached to behaviors and substances and reduce our cravings for those or our desire for those substances. So, you know, definitive trials are underway, but from the preliminary data and a lot of overviews of secondary analyses of trials, it looks like the whole spectrum from alcohol, drugs, tobacco, gambling, all those things that we associate with something that you use the word addiction to describe are affected in a positive way. And of course, when it comes to food, especially the consumption of ultra-processed food, it seems like a very similar set of issues in play.
Right. Well, let's say if GLP-1 therapies do fulfill their promise, what do you think could be their impact on public health over the next decade?
Well, you know, if I were cynical, which of course I'm not, I would say, you know, if you dropped down from Mars and looked at the human condition, you would say, "Why on earth did these people create an environment for food which led to a tremendous increase in overweight and obesity that could have been prevented had we just produced and eaten a good diet. And then we invent a drug that costs a fortune in order to reverse the effects of what we've created. That seems insane." But the fact is, this happened. As a society, we have gotten way overweight. And I'm just sitting here remembering I was just in a meeting earlier today about large clinical trials. And in the early days of my career, when we were doing enormous trials of treatment of heart attack and unstable angina and stroke, when we did the international comparisons, it was always obvious that the Americans weighed a lot more than people from other countries. And at first I thought, "Well, this is just we're bigger." But no, it's not that. It's we have a different dietary pattern and that has an effect. And so, given where we are today, if we could equitably distribute this class of drugs, and as we continue to work through these different pathways, we'll get better and better, more effective drugs. We could see a time where we reverse this chronic disease epidemic that we currently have. It's not only due to nutrition and overweight and diabetes, but it is the biggest driver. There's a great study from Global Burden of Disease looking at data that really shows it is the biggest driver of what's happened leading to this flattening of improvement in life expectancy that we've seen particularly in the United States, but also in other countries. But right now we're not distributing GLP-1s equitably. I'm reminded of a quote during the pandemic that related to technological solutions from Ed Yong, who was a great writer about the pandemic. And it went like this: technological solutions drift into society's penthouses. Diseases seep into society's cracks. And if you think about it, we had this early phase of GLP-1s when almost all of them were scarfed up by people who were either with a lot of money or who were very highly educated and you had a go and get them. And the people who needed them the most really had very little access. And we still have that problem.
Right. Well, that's something that we're going to dive into for sure. Before we do, I do want to ask you what do you think are some of the biggest risks if we fail to manage the rapid adoption of these therapies?
Well, you know, the good news is that all of this attention plus what's happened with Maha and I'll go all the way back to Michelle Obama. I remember being on stage with Michelle Obama when she really tried to work on the diet. But people are now increasingly aware that this is not a moral failing. This is a consequence of the policies that we have about food. So, I think even independently of the GLP-1s, we're likely to see a curbing of this very significant and dangerous trend in our health. But, we can get there a lot faster if we distribute the GLP-1 drugs well. And you know, the risk is mostly to people who are otherwise disadvantaged, who don't have good insurance, don't have spare cash to buy things direct-to-consumer, and may not have the influence to get their foot in the door in an environment where the cost of the drugs is still high enough that it's causing insurers and employers to not make them part of the plans.
