Pharmaceutical Development and Approval in the United States of Agents to Influence Cardiovascular Health

As knowledge about the pathophysiology of atherosclerotic cardiovascular disease (ASCVD) increases, research to investigate potential candidates for therapies that may reduce the risk of ASCVD events is expanding. The main candidates of therapeutic agents are small molecule drugs, which are chemically synthesized, and biologics, which are obtained from living sources. This chapter describes the drug development and approval process of the U.S. Food and Drug Administration (FDA). Drug development consists of multiple steps to ensure both efficacy and safety, including preclinical research, the Investigational New Drug application, clinical research studies (Phases 1, 2, and 3), the New Drug Application for new chemical entity pharmaceuticals (or a Biologics License Application for biologic compounds), and post-marketing surveillance (Phase 4). Approval of some categories of drugs requires undertaking a Phase 3 trial to demonstrate efficacy for reducing the risk of clinical events, such as a trial to demonstrate a reduced risk of major adverse cardiovascular events (MACE), referred to as a cardiovascular outcomes trial (CVOT). Particular attention toward assessing the cardiovascular safety of certain classes of drugs has also been recommended by the FDA. The FDA has provided guidance for the development of several types of agents that affect cardiovascular health including lipoprotein- and lipid-altering therapies, antihypertensive agents, as well as agents for the management of heart failure, type 2 diabetes mellitus, body weight, and nonalcoholic steatohepatitis.