An article by the Resverlogix team entitled "RVX-208, a BET-inhibitor for treating atherosclerotic cardiovascular disease, raises ApoA-I/HDL and represses pathways that contribute to cardiovascular disease" was just published online yesterday in the journal Atherosclerosis. It looks like this is an open access article, so all should have access. They cover the ability of RVX-208 (and other BET inhibitors) to increase apoAI mRNA synthesis and protein secretion in vitro, present the post-hoc analysis of the combined SUSTAIN and ASSURE trials (total population; not separated by diabetes, statin type, hsCRP level, etc), and microarray/pathway analysis of hepatocytes treated with RVX-208. This is all data that RVX has presented recently in poster or oral presentations at respected conferences, but the first time much of this data (post-hoc analysis of ASSURE/SUSTAIN and microarray analysis) has been published in a peer reviewed journal. Congratulations Resverlogix team!

Highlights

•Inhibitors of BET proteins show promise for atherosclerotic cardiovascular disease.

•BET inhibitors such as RVX-208 stimulate ApoA-I production in primary hepatocytes.

•RVX-208 leads to production of HDL.

•Preliminary clinical data show benefit of RVX-208 to lower CVD risk.

•Microarrays show additional benefit of BET inhibitors beyond HDL to reduce CVD risk.

Abstract

High density lipoproteins (HDL), through activity of the main protein component apolipoprotein A-I (ApoA-I), can reduce the risk of cardiovascular disease (CVD) by removing excess cholesterol from atherosclerotic plaque. In this study, we demonstrate that the bromodomain and extraterminal domain (BET) inhibitor RVX-208 increases ApoA-I gene transcription and protein production in human and primate primary hepatocytes. Accordingly, RVX-208 also significantly increases levels of ApoA-I, HDL-associated cholesterol, and HDL particle number in patients who received the compound in recently completed phase 2b trials SUSTAIN and ASSURE. Moreover, a post-hoc analysis showed lower instances of major adverse cardiac events in patients receiving RVX-208. To understand the effects of RVX-208 on biological processes underlying cardiovascular risk, we performed microarray analyses of human primary hepatocytes and whole blood treated ex vivo. Overall, data showed that RVX-208 raises ApoA-I/HDL and represses pro-inflammatory, pro-atherosclerotic and pro-thrombotic pathways that can contribute to CVD risk.