The beneficial effect of RVX-208 on patients with diabetes mellitus was accentuated with a relative risk reduction in MACE that was lowered by 77% (p=0.01). These observed reductions in MACE may stem from the ability of RVX-208 to significantly improve specific biomarkers of CVD risk measured in the SUSTAIN and ASSURE trials, including: higher levels of ApoA-I protein (p<0.01), an increase in HDL-C (p<0.001), more large HDL-particles (p<0.05) and growth in HDL particle size (p<0.05). The significant improvement in these biomarkers was in treated patients vs. placebo, which point to the beneficial effects of RVX-208 on reverse cholesterol transport.
RVX-208 acts via an epigenetic pathway and it is the first selective BET inhibitor being studied for treatment of CVD. The new information arose from the analysis of data pooled from the ASSURE and SUSTAIN clinical trials.
RVX-208 is a first-in-class small molecule that selectively inhibits BET bromodomains. RVX-208 functions via several mechanisms such as removing atherosclerotic plaque via reverse cholesterol transport (RCT), the natural process through which atherosclerotic plaque is transported out of the arteries and then removed from the body by the liver. RVX-208 increases production of Apolipoprotein A-I (ApoA-I), the key building block of functional high-density lipoprotein (HDL) particles and the type required for RCT.
These newly produced, functional HDL particles are flat and empty and can efficiently remove plaque and stabilize or reverse atherosclerotic disease. Analysis of recent clinical trials data showed that RVX-208 significantly reduces coronary atherosclerosis and major adverse cardiac events in patients with CVD who have a low level of HDL and elevated hsCRP, a population with unmet medical need.
ApoA-I enhancement and glucose lowering have been reported to exert beneficial effects in Alzheimer's disease and diabetes mellitus, respectively. RVX-208 also has anti-inflammatory effects including effects on Interleukin-6 inhibition, vascular cell adhesion-1 and monocyte chemotactic protein-1, factors known to be involved in atherosclerosis and plaque stability.
The above findings are valuable to Resverlogix because they put the company in an advantageous position in the emerging field of therapeutics based on BET inhibition," said Dr. Norman C.W. Wong, chief scientific officer of Resverlogix and also a practicing endocrinologist. "The data enhances the potential for RVX-208 to lower MACE in CVD patients and especially in those with diabetes mellitus. These key pieces of information will be used for the design of our next clinical trial that will continue the development of RVX-208 towards product registration."
Donald McCaffrey, president and chief executive officer of Resverlogix added, "We are very pleased to have this data highlighted at the ESC Congress. It underscores our plans to diversify the development of RVX-208 by studying its activity in additional indications. Moving forward, in addition to the clinical paths in cardiovascular disease, diabetes mellitus and Alzheimer's Disease, we are exploring other indications pertaining to chronic kidney disease (CKD), nonalcoholic steatohepatitis (NASH) and human immunodeficiency virus (HIV) lipodystrophy."
SOURCE: Resverlogix Corp.