WebMD's Chief Medical Officer, John Whyte, MD, speaks with David Ricks, chair and chief executive officer of Eli Lilly and Company, about the speed of drug development: Is it sustainable, and what do we need to make it happen?
This transcript has been edited for clarity.
John Whyte, MD: What health conditions are you most concerned about? Cancer? Diabetes? Alzheimer's?
It's critical to diagnose these conditions early and start treatment right away. But what about if we could prevent, cure, or even reverse them? Is that possible now or in the future?
Recently, I had the chance to sit down with David Ricks, chair and CEO of Eli Lilly and Company, at their global headquarters in Indianapolis.
We talked about the speed of drug development that we've witnessed over the past 3 years. Is it sustainable, and what do we need to do to make it happen? How are clinical trials changing, especially in terms of making it easier for people to enroll and being more representative of the population with the condition?
And what exactly does he mean when he says, "You need to lead with purpose"?
Dave, thanks for joining me today.
David Ricks: Great to be with you.
Whyte: Let's start off with what the COVID pandemic has taught us about drug development. There's been a lot of focus on vaccines, but there's been tremendous development in therapeutics, monoclonal antibodies, JAK inhibitors. Do you expect the innovation in drug development to continue in a post-pandemic world? Are we going to go back largely to the way things were?
Ricks: That's a great question. When I look back at my career at the end, that period during COVID will be one that really stands out because a few things changed across the sector. One is collaboration and partnership, both with the government — the FDA — as well as the White House Task Force and foreign governments, but also among pharma companies, where we collaborate from time to time. But in that period, there wasn't a week that went by that we weren't trying to figure out how to solve problems together, recognizing that when you have such an obvious present danger that people really did rally together to address the problem. How could we use that to think about an obvious and present danger that's always been with us, like cardiovascular disease or cancer? I think there will be a permanent impact of that, having gone through that, at least with this generation of leaders across government and industry.
Whyte: But how do you reconcile that with competition?
Ricks: I was just at a meeting with all of the industry leaders, who realize that actually the real competition is the disease, and that if we can get solutions faster, there's enough value for everyone to win. By focusing on what each of us does best, we could actually make more progress or have assets to bring to the table, and I think that will change — at least among Big Pharma companies — how we work together. Certainly, with the FDA, it changed things. We'll see about the other arms of government because they, I think, retreat more quickly to their corners.
I think the two most important things relate to the development drill for monoclonal antibodies, between discovery and the clinic, which we compressed from what is normally 3 years to about 3 months. Some elements of that we can continue to do. The other is clinical trial recruitment, where in this case we could no longer rely on big-hospital, famous institutions to find patients and then consent them and add them in with the normal process we use. We went directly to patients and skipped over the healthcare system in a lot of ways that will stick with us. We're actually doing a very large study in dementia prevention this way, and it's astounding how fast you can recruit people, because people want to contribute to research. But accessing healthcare is hard and sometimes intimidating. The other factor is how diverse the population was when we went direct to pay sharp vs the normal way.
Whyte: I'm an internist and I've always been interested in diabetes care. Your history is largely around diabetes. I think about where we are with diabetes care today: We're not just treating one disease, type 2 diabetes, particularly; we're also treating obesity, right? How did we get to this point?
Ricks: The innovation from the industry has been a steady drumbeat and probably accelerated in the past 20 years. When I joined the industry, I started in our diabetes group and we had insulin and sulfonylureas. Then we added metformin and it was like a miracle; that was an old drug from Europe. Then we started to see new therapies coming every few years. Now we have the incretins, which are really transforming diabetes because now we're not treating for holding patients or maybe delaying something bad. We can actually conceptualize, reversing the disease because we can reverse excess weight. That's a new dawn. Now, interestingly, despite the fact that in the past 20 years we've seen many more tools, you have many more tools as a clinician to treat the disease. Actually, the success in treating diabetes in America is not going anywhere: The percentage of patients who achieve the A1c goal of 7 or less is about 50% — the same as 20 years ago. And the percentage of patients who have obesity and have diabetes has actually risen in that period of time.
So we have this big gap between the tools that are now developed, newer tools like Mounjaro (tirzepatide), or new launches. On the other hand, using those tools is getting harder and harder apparently, because we're not getting clinical outcomes the way we need to. So as a company, we're committed to work with practitioners to fix that. If we have great tools, we need great outcomes.
Whyte: But do you think the innovation could be reversing type 2 diabetes?
Ricks: We do. So if you look at a product like tirzepatide, or Mounjaro, just launching for diabetes, we're studying it for obesity. You can see profound effects on weight, and weight is such a driver — not just of diabetes but of so many other chronic metabolic diseases: cardiovascular disease, even hypertension management, along with major cardiovascular events, stroke, heart attack, and congestive heart failure. These are huge categories of illness where still those with the number-one killers — cardiovascular disease and diabetes — have a four-times [higher] likelihood of a heart attack. Reversing that, if you could think of one risk factor, what would it be? It would be weight. And the first thing you say to every new patient is, "You probably should lose some weight." But it's hard. In our latest phase 3 study for this drug, there were two amazing findings. One got reported widely, which is that when on the drug at the highest dose, people lost 22.5% of their body weight — basically [like with] surgical intervention.
Whyte: Equivalent with bariatric surgery.
Ricks: Right. We can now envision a medical intervention that could reverse obesity.
Whyte: Let's talk about cancer care, oncology: 600,000 people still die from cancer every single year. Are we going to win the war against cancer? We've been talking about it for 50 — more than 50 — years.
Ricks: Everybody's focused on it. We're all affected by people who have cancer. My mother is currently in stage IV of an illness. So I see it firsthand. Cancer is many diseases. I think that's the challenge here. So to ask the question broadly isn't totally fair to the science, but I think we can see that in some disease states — take breast cancer or prostate cancer —30 years ago, life expectancy was quite short. Today they're not quite chronic diseases; you can die of other things. But getting close, we're seeing survival in people who have early intervention with adjuvant surgery and then treatment with hormone therapy. We have a new medicine that adds to that, in various stages of metastatic treatment. People can live a very long time — decades — with a cancer diagnosis now.
That was unheard of 20, 30 years ago, but it's piece by piece. And within the way we described tumors as an organ where it manifests, that's not even quite accurate because we know that there are oncogenes that are driving it that could be quite different in the same tissue. It's hundreds of different conditions. Already we can say that some of them we can manage for quite a long time as a chronic disease, but that's certainly far from the majority. More work needs to be done to peel apart that genetic work and create targeted interventions that are tolerable.
Whyte: In some ways, it's like diabetes care in the way that we've developed new agents. We've developed new ways of treating the underlying physiology. We've seen that in oncology, in terms of the different types of medications. But what's next on the horizon in terms of managing cancer?
Ricks: We get excited about general approaches, like immuno-oncology, which can help the body suppress tumor growth. We're very focused on targeted approaches that, again, peel off subsegments of the disease and really create profound difference. We launched a product that works on what's called RET mutations, which drive a single-digit percentage of lung cancer and several other types of cancer, and the duration on this therapy is years. For those people who have that mutation, we now have a really credible medical solution, but there are many types of lung cancer where we have not identified that driver, and we need to do that and then create targeted medicines that can address it. Both are the future, I think — more general approaches that can make more tolerable therapies that generally help control cancer. And then more specific ways. The final thing I'll say, like with diabetes, thinking about the precursor, can we catch cancers even earlier? Right now it's typically visually detected on a scan; surely that must be too late.
Can we get better using cells, using laboratory techniques, to look for protein markers in the blood?
There are exciting efforts underway to use those tools, not only to catch it early but also to monitor success and catch recurrence sooner. So the earlier we can intervene, the better we're going to do against cancer.
Whyte: Let's talk about Alzheimer's disease. Many people are concerned, as they get older, about memory loss, dementia. There have been a lot of misses in terms of drug development in Alzheimer's disease, but you're optimistic that there are going to be some hits, some positive outcomes. Why do you say that when, not that past is prologue, but we've been excited about potential therapies and then when they move from clinical trials to general practice, the real world, we don't quite see the same outcomes. But you feel differently this time.
Ricks: We do, and to be fair, we have yet to see a clinical trial except one which is on our drug phase 2 study, we unveiled last year, a positive hit in Alzheimer's. There are many failures — you're right. That's drug development in general. This one's been particularly painful, I think. The success rate is less than half of that in any other field. Neurodegenerative conditions are tough because we don't fully understand the biology of the brain. But with Alzheimer's we are optimistic because (1) we've been working on it a long time and we have a good understanding of the disease pathology, and (2) the precursor protein that's thought to cause the disease, called amyloid, we believe is a primary actor. And we believe that because although there have been lots of misses, they have all missed on the right side of the risk curve.
They all have reduced risk, but not enough. Through two types of innovation — the molecule we're testing and the way we test — we are going to get closer to proof. Next year will be exciting; we have our phase 3 readout. But the molecule itself we've been treating with anti-amyloid antibodies and other drugs for a while and just missing. Probably one of the reasons for that is they don't work deep enough; they don't get rid of enough amyloid and they don't do it fast enough. In an 18-month observation period for a chronic disease where amyloid accumulates over decades in the brains of the elderly, we can actually reverse that and see a clinical difference. So we need a fast-acting, deeply clearing antibody, and our medicine does that uniquely.
Whyte: You're taking a different approach than some others.
Ricks: Designing a better medicine. And in our phase 2 study, it was very positive: 32% reduction in symptoms after 18 months. We're trying to replicate that now. The other is designing studies in a precision medicine way that target the right patients. Clearly you need amyloid in your brain. We used to test these drugs without even looking at that.
Whyte: We didn't have good ways of testing that, too.
Ricks: There are many types of dementia; Alzheimer's is the most common, but it's not the only one. So we have to get people with amyloid, and then the other thing we've done is stop relying on clinical assessment tools or scales to categorize patients as early or late in the disease. It turns out that the scales aren't very good day to day; patients perform differently on those scales, and physicians aren't great at interpreting those differences between clinical sites. So we now scan the brain for the second protein, tau, which spreads with symptoms. We want to catch people who have a little bit of tau but not too much. They're in our studies, and hopefully we'll be able to come forward next year with a positive result and really start making a difference here.
Whyte: Let's talk about equity. I first want to focus on clinical trials, and you clearly say on your website that diverse representation is critical, but you go a step further than some of your colleagues. You specifically say on the site that people respond differently to medicines depending on age, sex, race, ethnicity. How did Lilly come to that recognition? Some people out there will be like, "You know what? There has been low representation for decades, so what's different now that Lilly is saying it's critical, and what are you going to do about it?"
Ricks: I think those statements are facts. I don't think they're difficult to understand.
Whyte: There are some people who don't agree that all of those elements matter.
Ricks: Well, not for every medicine. But across the pharmacopeia, we have to treat disease — certainly it's true. In every one of those cases, we can think of a medicine that behaves differently in men and women.
Whyte: It's variability of drug response.
Ricks: Our goal is to run a clinical program that can give — in a sampled way because we don't do census studies of the whole population — a view into how a drug can perform in the real world. Because our goal isn't successful clinical trials; our goal is successful outcomes for patients. That's our purpose, as a company. Then you have to embrace this philosophy that we need to understand those differences. Because in some cases you could provide minimal benefit and some harm; every drug has risk. We should eliminate those from the practice guidelines, from the indication statement. In some cases you might have exaggerated benefit, and there we should focus clinical treatment in that population. Why wouldn't we want to know that? We should want to know that, because in the real world, we want to find success and avoid harm.
I think there's an additional element, which is health equity as a societal expectation. COVID shined a really extreme light on that. And I don't think the US healthcare system is doing a very good job on health equity right now. One way we can contribute to improving that is providing data to clinicians, to understand those differences and have answers for patients about "What about someone like me? Is this drug effective? Is it safe?" So we take that on as responsibility.
Whyte: But historically it's been difficult to enroll minorities, people of color, in clinical trials. And the push in industry has been "let's reach recruitment." It can be a challenge because many trials never get to recruitment in the first place. So how do you reconcile those competing challenges? Are you going to hold people accountable in the company, that there needs to be a certain representation of minorities in different disease conditions? Because in the past, goals have been aspirational, right? We want to enroll a qualitative number. So how is it going to be different today? Because as you point out in COVID, there was an explicit expectation upfront that there would be a certain percentage, and it was designed to make sure that certain persons of color were enrolled. So what's going to be different going forward?
Ricks: Well, here again, I think the COVID experience was instructive. We set out with those goals in our therapeutics: trials and speed. We couldn't compromise on either, and you know what? We found a way to solve the problem. So I think that to accept this false premise that diversity in a trial will slow it down is accepting defeat before you start. We dismiss that. We start with the premise that we want diverse clinical trials. Our goal for every study we run is to have the diversity in the study and represent the incidents of the disease.
Whyte: I want to ask another question about equity in the field of oncology, because you talked about tumor markers, receptors, sending out the biopsy. But we know that that's not consistently done across the country, particularly in communities of color, particularly as you move away from academic medical centers, to be honest. So how do we ensure, in terms of cancer care, that patients, particularly those from minority populations, are getting the best treatment? Because we see that that's not always the case, particularly in lung cancer, breast cancer, and other areas.
Ricks: Yes, and I would put Alzheimer's in this category too. So for practice specialties that are highly concentrated in our well-known brand-name centers of care — I won't name them here; we know who they are: the big academic medical centers — oncology is one of those things. Neurology is another. Actually, when we recruit clinical trials, we see worse performance than in primary care, common diseases.
Whyte: Despite that they sit in ethnically diverse areas.
Ricks: Downtown areas. But they're not serving that local community. And here we have a two-way bias: how the institutions are set up to serve, whether it be the type of insurance they prefer to serve or just the way they present themselves; and on the other side, you have a bias in the community: "That's not an institution for me." So to break that down, we have to work harder to select clinical trial sites in more rural and different urban settings. And I think we have to do a better job on the health reimbursement side for clinical testing and novel therapeutics. It's also true when we launch a new cancer medicine. Uniquely, if you look at the demographic of who's using it, it looks like the clinical trial, which doesn't look like the country either.
And so there's tremendous bias in those systems for advanced care, and that needs the most work. We're committed to doing that. We have this RET-targeted drug that I mentioned before, which requires a genome sample. We're subsidizing tremendously that process so it's available to more Americans. And also educating — with your organization and others — clinicians on why it's always valuable to have more information, not less: Even if it's a 1-in-30 chance that this lung cancer has a RET mutation, you should know that because it changes the outcome for this patient.
Whyte: On your site, you talk about leading with purpose. What does that mean, practically, to listeners?
Ricks: I think it's an important development for us to really put that at the front. We've always been a purpose organization. If, 20 years ago, you walked the campus and asked people, "Why do you join us?" A scientist would say, "I want to make a new medicine for patients"; a physician would say, "I want to work on clinical trials that make a difference — bigger than one by one with a patient; I want to be able to affect the whole country." And commercial people would say, "Yeah, I want to work in a business, but I want it to be one that does good as well." But we probably have not surfaced that the way we need to, to engage and motivate our employees.
If you talk to Gen Z populations or people coming off college campuses, this isn't just like an extra thing that's nice; it's how they want to spend their life. And that unlocks energy of people here, but it also allows us to attract the next generation. Externally, society expects that there's a whole movement in business called ESG [environmental, social, and governance]: Are you stakeholder driven vs shareholder driven? This company was founded on that idea of stakeholder driven, making better medicines for patients, being a community leader, etc. So it just feels right to surface that to the top of our website and really say that we are powered by that purpose. When we make great medicines that have breakthrough potential, like Mounjaro in diabetes, we check all of those boxes. Employees are engaged about it; they're excited to come to work and work on it. Our likelihood of discovering more things like that goes up such that our partners in the healthcare system are excited to work with us because they want to work in something new that can really change things for their patients. And then society in general will have a better view of Eli Lilly because we're making a difference in real health problems. So it all comes together when we focus on purpose vs other business metrics or other things.
Whyte: You've been here more than 25 years, most of your professional life. What's different today than when you started two and a half decades ago?
Ricks: Many, many things. I mean, there are some things that aren't different. The company was founded on values of respect for people, excellence in our business, and being scientifically driven — those are all the same. But when I joined the company, this floor looked very different. It was a dining room just for executives; we wore a suit and tie everywhere, all the time; we put our jacket on to go to the cafeteria. There was a formality like you'd imagine in a Midwestern old corporation, which, frankly, got in the way of leaders in positions like mine now, understanding what's actually happening. And I think that's a hugely positive shift. We talked about diversity today, but this was a very male-dominated White company when I joined it. It's very different today; we have more females than males in the company today.
We have a very diverse workforce. We're better for it in every possible way. And I'm proud of that change. The other thing that's really shifted is that scientific origin we have has only accelerated. We think of ourselves not just as a leading pharmaceutical company scientifically, but as a leading organization scientifically. We spent a lot of money there — $7 billion last year on R&D puts us on top of the league tables, and almost every measurement is a meaningful percentage of the NIH's total budget. But actually, the tools we're using, how we're using them — I think we're really on the cutting edge of science. And we're really proud of that. We're never going to stop innovating in clinical development, and I think that's exciting.
Whyte: Dave, I want to thank you for taking the time today to talk to us about innovation and drug development, as well as what you see as the future, in terms of how drugs are developed. .
Ricks: Thank you for having me. Great to be with you.
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Cite this: Change Makers: David Ricks Is Leading With Purpose - Medscape - Aug 22, 2022.