Abstract 18435: RVX-208: An Orally Administrated Small Molecule Reduces Atherosclerosis in ApoE Null Mouse and Raises ApoA-I/HDL in Humans

RVX-208 increases apoA-I production in vitro and in vivo. In preclinical animal models RVX-208 raises; plasma apoA-I, HDL, pre-beta HDL, large alpha HDL while promoting SR-B1-, ABCA1-, and ABCG1-mediated cholesterol efflux ex vivo. These changes in biomarkers of reverse cholesterol transport suggest that RVX-208 may be antiatherogenic. To test this possibility, apoE null mice were given a high-fat diet and 150 mg/kg of RVX-208 or vehicle b.i.d. for 12 weeks. In RVX-208 treated mice the plasma HDL-c levels were 2-fold (p<0.01) higher vs. vehicle. Additionally, biomarkers of inflammation; VCAM-1, IL-18 and MIP-1α were 17, 15 and 21% lower in treated vs. vehicle, respectively. Numbers of atherosclerotic lesions in the aortic sinus and thoracic aorta were 28% (p<0.01) and 17% (p<0.05) lower in treated mice, respectively. A phase 1b/2a human trial of RVX-208 included a low (2 mg/kg/d) and a high dose (6 mg/kg/d) of RVX-208 given to 18 subjects and 6 placebos per arm for 28d. Plasma apoA-I levels rose significa...