Pablo Lapuerta is the Executive Vice President and Chief Medical Officer of Lexicon Pharmaceuticals. Prior to joining Lexicon in 2011, Dr. Lapuerta served as vice president at Bristol-Myers Squibb, working on the global development of an Alzheimer’s disease drug candidate, for 11 years before joining Cogentus, where he served a host of executive roles with a focus on clinical strategy and development. His recent work in genetics and drug development have yielded a potential treatment for Type I diabetes that has been approved in Europe for clinical use. Dr. Lapuerta graduated from Harvard College summa cum laude with a B.A. in Biology and holds an M.D. from Harvard Medical School. At the 45th International Conference, Business Today spoke with Dr. Lapuerta about the direction in which the pharmaceutical and biomedical industries are headed with the rise in ethics discussions and technological innovation.

Arjun Jagjivan (BT):  As an executive in the pharmaceutical industry, do you believe that having a medical degree gives you an advantage over someone with an M.B.A. or a degree in finance?

Pablo Lapuerta (PL):  Being a Chief Medical Officer has been a great experience, and that is where an MD is very important. A commonly sought opportunity in the industry is to become a Chief Executive Officer, and that is open to physicians, especially in small biotechnology companies. The small venture capital firms have people with M.D.s and P.h.D.s, and a lot of the first-time CEOs possess M.D.s or P.h.D.s. Where the M.B.A. becomes more important is in large pharmaceutical companies because they have existing sales, and that sales piece is very big to them, and it is more common among people who have entered the industry through the business side, many of these individuals eventually getting the M.B.A. A good part of the MD is that it helps me with the long term perspective, having a vision of the drug in practice changing patient lives. That long-term perspective is closely linked to the ethics of the profession. A team that has a long term vision is a team that will follow an ethical pathway, and that is a team that has a good foundation for success. 

BT:  When it comes to ethics, the pharmaceutical industry has received backlash for skyrocketing drug prices. How do you think people in the industry can shift this narrative to show that monetary profit isn’t the defining factor in drug development?

PL: The pharmaceutical industry can do a lot to help people understand drug development, and that is necessary to understand pricing. I’ve seen efforts like TV commercials that display America’s biotech researchers, and they show people in labs who are driven and inspired. We can go beyond that and bring the perspective even into the marketing of specific products. Think about Entresto, a drug that lets people with heart failure live longer lives.  I don’t know if you’ve seen their advertising, but their pitch is that you have more tomorrows with Entresto, and they use the song from Annie, “Tomorrow.” But in an Entresto campaign, why not have one of the scientists who developed it? Why not mention how many clinical trials were done, or how long it took to develop? How about “after 10 years of development and clinical studies in 10,000 people …” I think that type of messaging can be done and would help people really understand what it means to have a new innovation on the market.

BT:  When it comes to working with the FDA in approving prescription drugs, what are some of the challenges you face, and where do you see potential improvements in this collaboration?

PL:  I think the FDA is very proud of how they protect the public from harmful drugs. The FDA also needs an incentive to be proud of timely drug approvals.  There was a recent letter to the editors of the Wall Street Journal talking about this; it was actually from a former FDA staffer who was involved in the approval of the first human-derived insulin. It was a great breakthrough in the 1980s. The FDA staffer was so excited about the first human insulin that he tried to set a record for the speed of drug approval.  After about 4 months, he was ready to have it approved. He worked closely with the sponsor and he presented it to his boss, and his boss said no. The boss said, if this gets approved so quickly and there’s any problem with it, the people will blame us, and he refused to take action. That shows you the kind of struggle the agency had in the 1980s, not having the mindset to be proud of timely approval of an effective drug. Even today, the FDA can do a better job in celebrating and rewarding those who are willing to step out on a limb and get effective drugs approved efficiently. 

BT: How are the names of prescription drugs designed? Is marketing taken into consideration when drafting up options?

PL:  In general, people work with agencies that specialize in this, and they come up with a bunch of positive names.  They’ll try to come up with a play on something people will respond to, so in the case of Entresto, the marketing person may have been thinking about trust. Some of these names try to suggest a benefit, and they can’t be too close to be approved.  They come up with a big list, and they submit it to the agency and see if they will approve it. The agency approved Entresto, [but] probably would not have approved Entrusto.

BT:  Lexicon has recently been working on a drug called sotagliflozin as a treatment for Type 1 diabetes, but it has yet to be approved before it becomes commercially available.  What goes into the process of developing new treatments at Lexicon, and how do you minimize error when conducting trials?

PL: We have extensive quality control to ensure that there are no errors. Quality is important because we want to ensure the highest probability of approval.  At Lexicon we also enhance our probability of success by targeting serious diseases with high unmet needs, and that’s one of the reasons that we studied sotagliflozin in Type 1 diabetes. There are about 12 different types of approved drugs for Type 2 diabetes. For Type 1, there are only two, insulin and another injectable agent that is seldom used. So there is a huge need to go beyond insulin, and we saw some characteristics in sotagliflozin that were well suited to people with Type 1 diabetes.  We had a vision that sotagliflozin could reduce hypoglycemia in Type 1 diabetes, which is a major cause of mortality, and sure enough, we saw less hypoglycemia in the program when we added our drug to insulin than with insulin alone. We’re very pleased that we got approval in Europe for the treatment of Type 1 diabetes: this year, both dapagliflozin and sotagliflozin were both approved, the first oral agents ever for patients with Type 1 diabetes, both used as an adjunct to insulin. We’re very proud of that, and that sort of vision was relevant to our success.

BT:  The growth of technology has been rapid in the last decade, and data analysis has become a hotspot in medical research. Could describe how biomedical advancements have affected your field of work?

PL:  Technology around us has changed so much that we can do better clinical trials and capture the patient’s voice better in ways that are safer for patients, and that has fundamentally changed what we do. In our first Type 1 diabetes study, we wanted to monitor glucose values better than anybody had done before, and what we had found at that time, which was about 6 years ago, there were these glucose meters that as soon as you got a value, the result was sent to the cloud; your glucose meter was essentially acting like an iPhone. We gave everyone the same glucose meter and had them give us anonymized access to all these accounts, and we were able to follow every person’s glucose as soon as they measured it. When you do a typical clinical  trial, you often don’t see results like that for one or two or three weeks, but we saw them instantly. I believe the clinical trials are better monitored and much safer because of advances in technology like wearable devices…

BT:  In its early stages, Lexicon focused primarily on genetic technology. With access to the wealth of information now available from the Human Genome Project, what are the prospects for Lexicon in the realm of genetics?

PL:  The fundamental technology that Lexicon developed was in the 1990s which was an efficient way of developing what we call gene knockout mice.  You could develop a family of mice that were missing only one gene, and you could control which gene that was. Lexicon developed almost 5,000 different families of these mice each missing only one gene, each being a different gene covering what Lexicon projected was approximately 5,000 genes in the mouse that had human counterparts. We had a mouse that was more resistant to diabetes and that led to the development of sotagliflozin; when we gave the mouse a meal, the glucose wouldn’t go as high as other mice, and yet the mouse was healthy. There’s a mouse at Lexicon that is more resistant to pain, and that has led us to develop a new type of pain relief medication that is a new class of compound that doesn’t rely on any pathway related to opioids. So we’re excited about that because we may be able to have an impact on the opioid epidemic. That’s exciting technology that still has a lot of opportunity for drug exploration.