Clinical imaging in anti-atherosclerosis drug development. Issue 11 (November 2015)

• Record Type: Journal Article
• Authors: Ehlgen, Alexander; Bylock, Anders; Kreuzer, Jörg; Koslowski, Michael; Gantner, Florian; Niessen, Heiko G.
• Is Part Of: Drug discovery today. Volume 20:Issue 11(2015)
• Page Start: 1317
• Page End: 1327
• Publication Date: 2015-11
• Subjects: Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2015.06.014
• Languages: English
• ISSNs: 1359-6446

Abstract

Highlights: There is a need to de-risk expensive Phase III outcome trials in atherosclerosis. Imaging can be of high value to de-risk large Phase III investments. Imaging is ideally used in Phase II to identify signs of efficacy. The predictive value of imaging for atherosclerosis modulation is however unknown. Abstract : The development of novel drugs for the treatment of atherosclerosis faces many challenges, particularly caused by the need for large and costly outcome trials. When predictive biochemical biomarkers are not available, clinical imaging data can serve as intermediate Phase II endpoints to demonstrate mechanistic and anti-atherosclerotic activity of new compounds. These data can support risk mitigation before continuing development in large Phase III outcome trials. Imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT) and ultrasound [intima-media thickness (IMT) and intravascular ultrasound (IVUS)] can provide detailed information on vascular plaque volume and morphology, whereas functional changes can potentially be captured by positron emission tomography (PET) techniques in the vessel wall. We will review the application and operational aspects of clinical imaging methods and endpoints used in interventional atherosclerosis trials. Teaser: In anti-atherosclerosis drug development clinical imaging data can serve as intermediate endpoints enabling informed decision making and risk mitigation before entering into large Phase III outcome trials.