For as long as he can remember, David Soergel has liked tinkering with things and understanding how they work. The Head of Drug Development for Cardiovascular, Renal and Metabolic Diseases at Novartis believes that this early inclination toward research was key in shaping his aspiration for discovery and learning. As a high schooler, Soergel secured a post in a laboratory at the National Institutes of Health (NIH) in Bethesda in the US state of Maryland. “I just loved everything about it – the environment in the lab, running experiments, interpreting the results, communicating them, and then figuring out what to do next.” At the NIH, he also realized that by developing new therapies and advancing science he could unravel a momentous event that had marked his childhood. Soergel still vividly recalls the details of this particular afternoon: waiting for his father to come home from a business trip, finding out that he had suffered a heart attack, the frustration of not being able to understand what had happened. “Everything was shrouded in mystery,” he remembers. “Nobody talked to me and my brother about it. All we knew was that dad was sick. It took me weeks, months, years to grasp what was going on.” Soergel’s father lived with the consequences of his heart attack, and Soergel went through that health journey together with him as he was growing up. “Back then, I tried hard to understand what he was going through: the arrhythmias, eventually heart failure. It was from an empathy standpoint at the time.”

Though he did not come from a family of doctors – he didn’t even know any physicians during his childhood – going on to study medicine was the logical next step. He was drawn to cardiology as it was image-based and quantitative, he explains. “Later on, I gravitated toward pediatric cardiology, where there is an extra dynamic. It is not only the patient, but also the family that you guide through a crisis, be it big or small.” During his training in heart failure and transplant medicine, Soergel also discovered the importance of teamwork. “As a physician, what you bring is your knowledge of medicine, science, clinical care and team leadership. But you fundamentally rely on the pharmacologist, nursing staff, physical therapist, social worker, nutritionist … all these people work together to help patients and their families transition to the next stage in their life.” As part of his work in transplant medicine he came to cherish how an engaged and committed team can fundamentally change a patient’s life. But his curious mind did not stop here as Soergel’s interest also pivoted toward drug development. “It’s not common, at least in the United States, to go from academic training in medicine to a pharma company. But I was interested in exploring this option.” Soergel was not fully convinced about this step, however – at least initially. “I walked to the building, scanned my badge and beeped in. As I stepped through the sliding doors and they closed behind me, my only thought was: I can always go back!” This was 20 years ago, and Soergel never went back. “I love what I do, and I am amazed by the impact that we can have in pharma companies. The scale at which we are changing people’s lives is tremendous.”

Interview with David Soergel

David Soergel: "Clinical trials are critical to improve outcomes in cardiovascular disease."

Mr. Soergel, cardiovascular disease is the leading cause of death globally. Still, have there been improvements in cardiovascular outcomes compared to the past? Over the last 40 years or so, there has been a transformational improvement in cardiovascular outcomes. This has been achieved through public health interventions, like smoking cessation, and through new drug developments, such as lipid-lowering agents, known as statins. Also contributing to this success are antihypertensives and better blood pressure control, as well as the adoption of guidelines to help practitioners better target diseases. What was the effect of these measures? All this has taken the mortality rate down by about 75 percent. But that doesn’t mean the problem is solved. Cardiovascular disease kills 18 million people across the world every year. The majority of cardiovascular disease is related to so-called LDL cholesterol, which is commonly referred to as bad cholesterol. So there continues to be a need for even better ways to improve cardiovascular risk management. What specific challenges come with treating bad cholesterol? Diseases that are asymptomatic, such as elevated cholesterol, are difficult to manage because patients often struggle to remember to take their medicine. When they are taking their statin, for example, they don’t feel any better than they do after they stop taking it. But the risk goes up exponentially. After a heart attack, which is one of the most life-changing experiences, almost all patients get started on high-intensity statins because it’s been shown to improve outcomes. A year later, less than half of the patients adhere to the therapy. Many people simply don’t like taking medicines. Have there been any advances in making it easier for patients to stick to their regimen? The next generation of treatments is already here – instead of having to take statins every day, you can have a shot at your doctor’s office, a sort of take-it-and- forget-it approach. This takes patient adherence out of the equation, and I think it will become much more appreciated over time. It is like with the iPhone: When you had a flip-phone, you didn’t realize you needed an iPhone. I think this next generation of medicines has incredible potential. How has the industry advanced in the renal disease arena? There hasn’t been a whole lot of innovation in renal diseases in the past 40 years – the last big one was probably the development of ACE inhibitors and ARBs, and that was a long time ago. But important things have happened recently. Can you specify? Basic science has advanced, so we understand the disease pathophysiology a bit better. Biomarker development has led to a better understanding of how you can measure renal damage effectively: Rather than doing a kidney biopsy every time to know what’s going on with a kidney, you can measure markers in the urine. The third advance has been that regulators are more amenable to those biomarkers as the basis for accelerated approval in some indications. Those three things have led to a lot of innovation in renal drug development in the last five years. What does the innovation landscape look like in the field of clinical trials? Clinical trials involve a complex interaction between patients and investigators engaged in clinical research. They take years: In cardiovascular disease, it’s probably seven to ten years from discovering a molecule, through testing it in the clinic, to the molecule becoming a medicine. There is no shortcut from the lab to a drug getting to patients and making an impact on public health. And it is upon us to increase awareness in that regard because the more awareness we create, the more people will want to participate in clinical trials. So, is awareness about clinical trials low? Awareness about clinical trial participation is very low, with less than 5 percent of eligible patients participating in a trial. Also, only 5 percent of physicians participate in clinical trials. The number of people and the number of investigators in clinical research is not high enough. People need to be more aware of what is going on. And we need to democratize clinical trials: get to more centers, make things easier for investigators and patients to enroll in studies. Why do you think patients are reluctant to participate? I think the stories that reach the public often focus on the disasters, about things that go wrong in clinical trials. You don’t hear about all the successes – they are typically featured in the trade press or medical journals. And most people don’t read medical journals, so there is a kind of patient bias. We have to be better at explaining what we do. What would an increased awareness of clinical trials lead to? If more people were willing to enroll in trials more quickly, and if we could make that process more efficient, it would reduce the timelines to get new medicines to patients. This is especially important in cardiovascular trials. A typical atherosclerosis trial involves between 10000 and 15000 patients, and it runs for five to six years. How could people become more aware of the importance of clinical trial participation? For example, when a patient goes to see their cardiologist, and there’s a new medicine available, they could talk about the process that went into creating that medicine. Then they could see whether the patient would be willing to participate in the next trial. People trust their own physician more than anyone else. Is there anything that could accelerate clinical trial recruitment? I think the medium- to longer-term approach has to be the democratization of trials. This means that patients wouldn’t be required to go see a provider at an academic research center – one of the 5 percent of physicians who participate as investigators. They should be able to go to their local doctor to participate. Although this approach hasn’t been fully realized yet, there are significant efforts going on, both within and outside of Novartis, to try to democratize clinical research. I think this offers the highest probability, especially for large indications like cardiovascular disease, where you run large, long trials over many years. Could participation in clinical trials be simplified for patients? We ran a pediatric heart failure trial recently. There aren’t that many centers that are specialized in pediatric heart failure, so patients had to drive four hours to get to a research center. We tried to figure out ways to make it easier, for example, by going to them, or having their local lab be able to do the necessary tests. Face-to-face engagement is burdensome for a lot of people in these studies. COVID made some of this a little easier, with telemedicine and interacting with people by video. Hopefully we can carry forward some of those innovations. Digital and data techniques can help in finding patients or following them through the study. Could more be done to enhance the way medicines are developed? We can do better in identifying which patients still haven’t benefited from medicines. There are patients that we can identify by using genetic risk scores, or through other biomarkers. They could potentially benefit more than the aggregate population. Perhaps this could lead to developing medicines specifically for those patients. There are things we can consider that would enhance our ways of developing medicines. But the fundamental process is probably going to stay the same. And from an investigator perspective, what can be done to simplify the process? Our clinical trial processes are very burdensome to investigators. There are video trainings, click-throughs, data entry and so on. We have been looking at ways to extract data directly from electronic medical records, for example. What are some innovations that have contributed to more efficient clinical trials so far? There have been important incremental innovations, for example, electronic data capture systems are a lot better now than they were 15 years ago. The process for packaging and sending lab kits to sites is a lot better. How we randomize patients has improved. There are many things that have been improved using web technology, or IVR – interactive voice response systems. Will this solve the challenge? To really get from the 5 percent up to 10 or even 15 percent of practitioners participating in trials, we have to do more. It’s a workflow exercise. I bet most practitioners will say: “I just don’t have time to do it. I don’t have time to spend half an hour explaining a trial to a patient, only for them to say no or yes. And then I don’t have time to do all the training. I don’t have time to figure out how to get the medicine. I don’t have the support.” So I think it is important that we look at our processes for working with investigators and make participation easier. This could help move the needle and be a boon to patients – especially in the cardiovascular space, which requires huge patient numbers to test new compounds.