Abstract 13654: Gemcabene Monotherapy and in Combination With Atorvastatin Lowers High Sensitivity C-Reactive Protein (hsCRP) in a Phase 2 Clinical Trial

Abstract

Background: It is well established that inflammation plays a key role the progression of atherosclerosis and that serum high sensitivity c-reactive protein (hsCRP), may be a good marker of the degree of underlying vascular inflammation. Thus hsCRP has been recognized as a predictor of cardiovascular risk and lipid lowering drugs, such as statins, which also result in a reduction of hsCRP may be more likely to reduce cardiovascular events. Gemcabene is an inhibitor of hepatic cholesterol, triglyceride, and apoC-III synthesis resulting in decreased assembly of VLDL and enhances the systemic clearance of VLDL and its subsequently production of remodeled lipoproteins including LDL. Study Design and Results: In an 8-week double blind randomized, placebo-controlled, dose-ranging, efficacy and safety Phase 2 study, gemcabene 300, 600 and 900 mg/day administered as monotherapy or in combination with atorvastatin 10, 20 and 80 mg/day resulted in a significant and dose dependent reduction of LDL-C (Study 4141001). A secondary objective of this study was to evaluate the modulation of hsCRP by gemcabene. Of 277 patients randomized, 250 (90%) completed the study. Baseline mean LDL-C was 174.7mg/dL, and median hsCRP = 2.5 mg/L. The median % reduction in hsCRP with Gemcabene 300, 600 and 900 mg monotherapy was 25.8%, 41.5% and 35.3% respectively compared with 9.4% for placebo. The rank-transformed data showed significant difference favoring gemcabene over placebo in the 600 and 900 mg groups (p=0.0070 and p =0.0018, respectively). Co-administration of 300, 600, and 900 mg gemcabene with atorvastatin aggregated over the dose range showed decreases in hsCRP beyond atorvastatin monotherapy (which ranged from 27-41%) by an additional 16% (p=0.0237), 23% (p=0.0017) and 28% (p=0.0001), respectively. Conclusions: Gemcabene significantly lowered hsCRP alone and on top of statins in hypercholesterolemic patients.