Landscape of innovation for cardiovascular pharmaceuticals: from basic science to new molecular entities

STRUCTURED ABSTRACT Purpose: Since the 1960s, the dramatic reduction of mortality from cardiovascular disease (CVD) in developed nations has been a major success of modern medicine. Some of the earliest therapeutics were developed from phenotypic observations and development of recent drugs to treat CVD encompasses the modern era of FDA regulation and reform, and advances in biotechnology. Recent reports have highlighted a lag in the emergence of new cardiovascular therapeutics, focusing primarily on issues related to the timelines and cost of preclinical, clinical, and regulatory development. This study examines the complete timelines of translational science for new cardiovascular therapeutics, from the initiation of basic research leading to identification of new drug targets, through clinical development and FDA approval of new molecular entities (NMEs) based on this research. Methods: This work extends previous studies by examining the relationship between the growth of research on drug targets and approval of NMEs associated with these targets. Drawing on research on innovation in other technology sectors, where technological maturity has been shown to be an important determinant in the success or failure of new product development, an analytical model was used to characterize the growth of research related to the known targets for all 168 approved cardiovascular therapeutics. Findings: Categorizing and mapping the technological maturity of cardiovascular therapeutics show that 1) there has been a distinct transition from phenotypic to targeted methods for drug discovery, 2) the durations of clinical and regulatory processes were significantly influenced by changes in FDA practice, and 3) the longest phase of the translational process was the time required for technology to advance from initiation of research to a statistically defined established point of technology maturation (average 30.8 years). Implications: This work shows a normative relationship between metrics of research maturation and approval of new cardiovascular therapeutics, and suggests strategies for advancing translational science by accelerating basic and applied research, and improving the synchrony between the maturation of this research and drug development initiatives. Key words Cardiovascular disease Cardiovascular therapeutics Innovation Drug discovery Drug development Quantitative modelling Chemical compounds studied in this article: Ezetimibe (Pubchem CID: 150311) Verapamil hydrochloride (Pubchem CID: 62969) Captopril (Pubchem CID: 44093) Propranolol (Pubchem CID: 4946) Losartan (Pubchem CID: 3961) Rivaroxaban (Pubchem CID: 9875401) Eplerenone (Pubchem CID: 443872) Furosemide (Pubchem CID: 3440) Conivaptan hydrochloride (Pubchem CID: 216322) Clofibrate (Pubchem CID: 2796) Riociguat (Pubchem CID: 11304743) Ivabradine hydrochloride (Pubchem CID: 3045381) Lepirudin (Pubchem CID: 118856773) Lovastatin (Pubchem CID: 53232) Lomitapide mesylate (Pubchem CID: 11274333) Aliskiren (Pubchem CID: 5493444)