Outgoing CEO of Swiss pharmaceutical and drug maker Novartis Joe Jimenez (L) shakes hands with incoming Novartis CEO Vasant Narasimhan during the annual results 2017 press conference in Basel on January 24, 2018.
Ruben Sprich—AFP/Getty Images
By Vas Narasimhan
March 12, 2018

Heart disease remains the number one cause of death worldwide, accounting for more than 30% of all global deaths. Yet the discovery of new cardiovascular medicines is at its lowest point in decades and represents less than 10% of global research and development spending.

Heart disease runs in my family—I have watched as close loved ones died suddenly from heart attacks or slowly over time from heart failure. As a physician-scientist who has led an R&D organization, I ask myself: Why is it that medical innovation in this area has stagnated, even as innovations in other therapeutic areas have increased?

Part of the answer lies in the history of innovation that significantly improved our standard of care over the last few decades. Thanks to new medical discoveries, we made significant progress in addressing many heart-related conditions that affect millions of people, such as high cholesterol and high blood pressure. Demonstrating a meaningful benefit over these medicines, while satisfying the current research and regulatory requirements in cardiovascular diseases, often requires large-scale clinical trials with thousands of patients over many years. When a new cardiovascular medicine is approved—even if it is a breakthrough innovation—commercial uptake can be slow, with budget concerns often overriding patient benefits. These challenges make drug discovery and development increasingly risky and cost-prohibitive.

It is in the best interest of patients, doctors, and society to have access to life-saving innovations to treat heart diseases. To ensure this access, we need a shift from broad-based development strategies to a more focused medicines approach in cardiovascular diseases. And for this shift to be sustainable, all players in the health care ecosystem, including regulators and payers, must reimagine their current approach.

First, we as pharmaceutical companies need to get better at applying a precision medicine approach in cardiovascular disease, similar to oncology, where it has already demonstrated significant patient benefit. Precision medicine means identifying the patients most likely to respond to therapies using proven targeting methods, such as genotyping or phenotyping. This, in turn, can make it possible to obtain robust data from smaller and more homogenous populations. It also means identifying and tracking biomarkers—naturally occurring molecules, genes, or characteristics that help us to identify diseases and specific pathological or physiological processes—during the course of treatment so that patients’ responses can be monitored in more real-time and treatment can be adjusted depending on the outcome. For large-outcome studies, it means introducing innovative trial designs that combine technology and real-world evidence to accelerate development timelines. Together, such changes could help us to deliver transformational medicines that are more meaningful to patients and health care providers.

Second, we need to unleash the full potential of today’s scientific advancements and sophisticated analytical tools that make it possible to uncover valuable information from large-outcome trials to inform patient care. Our current health care ecosystem isn’t set up to readily recognize scientifically robust subgroup data—which shows us the effects of treatment on specific populations within a broader study—in cardiovascular drug approvals, even if it comes from large-scale, multi-year studies—unless the group developing the treatment pre-identifies specific comparisons. Regulators should consider evolving their policies and guidelines to enable them to more fully reflect on the merits of such findings when making key decisions and establishing product labeling, similar to emerging regulatory guidance on the use of real-world evidence. This could mean accepting data from more targeted patient groups. It could mean considering new scientific evidence, such as additional surrogate biomarkers, which are two biological aspects of a disease that are proven to be associated—allowing you to study one (the surrogate) and make scientific conclusions for both based on the association of the two to support regulatory decision-making. This is a common practice in other medical areas like diabetes. It could also mean embracing new technologies—an area where we are seeing strides with the creation of a Center of Excellence on Digital Health within the FDA, which will provide digital health oversight.

Take, for example, the Novartis Phase III CANTOS trial—a six-year landmark study of more than 10,000 patients, which met its primary endpoint and showed, for the first time in history, that targeting inflammation reduces cardiovascular risk in people who survived a heart attack. All patients who entered the study had excess inflammation, which put them at an increased risk of another event such as a heart attack, stroke, or death. When evaluating the results, researchers found that certain patients achieved a much greater cardiovascular risk reduction than the overall population while—importantly—maintaining a similar safety profile, which means the safety of the therapy was comparable to the broader study population. These were patients whose inflammation level dropped below the entry criteria of the study, as measured with a simple blood test after the first dose of treatment. This exciting finding opens up the possibility that in the future, doctors may be able to identify and target patients most likely to benefit from long-term therapy, which can further inform their treatment decisions and lower costs.


Finally, by bringing life-saving medicines that are highly targeted to patients who can achieve optimal benefits, we can not only improve public health outcomes—we can also limit the financial impact on the overall health care system. In return, we hope that payers and policymakers involved in reimbursement decisions of value-based medicines will start to remove some of the legacy barriers that have been put in place to control budget impact of widely used medications of the past.

Globally, this could mean designing reimbursement strategies to address the needs of patients who derive the most benefit from new therapies. In the U.S. specifically, it could mean easing prior authorization requirements or reducing out-of-pocket Medicare costs for seniors who suffer the most from cardiovascular disease. These changes would make it easier for physicians to prescribe—and patients to obtain—the life-saving therapies they need.

There’s been much discussion on this topic, but the time to act is now. We must work together—payers, regulators, policymakers, and industry—to challenge old paradigms and reimagine the way we bring transformative cardiovascular medicines from the lab and into the lives of people who need them. Our patients deserve nothing less.

Vas Narasimhan is CEO of Novartis.


You May Like