Commentary on R&D Trends Away from General Medicine/Cardiovascular Drugs: Can the FDA Help Reverse the Trend?

Abstract

In the latter part of the 20th century, drug development in cardiovascular diseases (CVDs) was a paragon of "modern" therapeutics, bringing about a substantial number of effective, well-tolerated agents targeting some of the most prevalent diseases of the Western world. These drugs were often examples of rational drug development targeting specific pathophysiologic pathways previously elucidated through basic research (e.g., targeting of the renin-angiotensin system or the cholesterol synthesis pathway). The widespread adoption of these ground-breaking medications in practice and into medical guidelines undoubtedly played a role in the fall of morbidity and mortality from CVD in the United States in recent decades. For instance, the combined, age-adjusted rates of death due to heart disease and CVD fell in the United States from an aggregate of 329.6 per 100,000 in 1999 to 203.5 in 2014. Although lifestyle trends (e.g., decreased smoking prevalence) contributed to this decline, the impact of safe and effective medications for common CVD conditions cannot be dismissed. Yet, despite the drop in CVD morbidity and mortality, CVDs remain a leading cause of morbidity and mortality in the United States and, therefore, a large area of unmet medical need.

Affairs of the Heart: Innovation in Cardiovascular Research and Development

“…As illustrated, there were no cardiovascular drug approvals in 2016 or 2017 as of the time of this writing. In this issue, Kesselheim and colleagues, Ringel et al ., and Meyer all offer further insights and interpretations of this temporal phenomenon . Regardless of the reason, medical needs for new safe and effective cardiovascular therapeutics remain high both for conditions with available medicines as well as for those with unsatisfactory options.…”

“…In either case, are the clinical research enterprise and regulatory pathways enabled to facilitate and expedite their development? In addition to expedited regulatory pathways that are currently at the disposal and oversight of the FDA, the European Medicines Agency, and other regulators, Meyer eloquently notes that FDA experiences with proximal biomarkers have informed an expectation of demonstration of empiric benefit for cardiovascular drugs . While some surrogate biomarkers do support approval (e.g., blood pressure, LDLc, HbA1c), regulators do not yet embrace broad use of endpoints “reasonably likely to predict clinical benefit” and support accelerated approvals of new medicines.…”