Resverlogix Corp. announces the commencement of dosing in SUSTAIN, a new phase II b clinical trial led by the Cleveland Clinic. SUSTAIN will enroll 172 subjects with established cardiovascular disease (CVD) who continue to have a high-risk for recurrent CVD events. All subjects in SUSTAIN will have a low level of high-density lipoprotein cholesterol (HDL-C) and are receiving standard of care therapy that includes up to 40 mg Atorvastatin or 20 mg Rosuvastatin. SUSTAIN subjects will receive 200 mg/day of Resverlogix's lead compound RVX-208 or placebo in a 24-week, multi-centre, double-blind, randomized, parallel group, placebo controlled clinical trial in order to assess lipid trends and safety.
In addition, other biomarkers of reverse cholesterol transport (RCT) will be examined. The primary endpoint of SUSTAIN is the change in HDL-C from baseline after receiving RVX-208 for 24 weeks vs. placebo. Secondary endpoints include change in ApoA-I, LDL-C, non-HDL-C, apoB, TG and HDL subclasses. The SUSTAIN trial will be conducted in South Africa.
The SUSTAIN trial is independent of ASSURE, a phase II b clinical study using intravascular ultrasound (IVUS) technology to assess atherosclerosis.
“We have learned several valuable lessons from the on-going analysis of our recently completed ASSERT phase II trial,” commented Dr Jan Johansson, Resverlogix's senior vice president of Medical Affairs. “The ASSERT population was comprised of all patients who had stable CVD given standard of care therapy including statins. The continued analysis of the ASSERT data revealed that subjects with low HDL who received targeted doses of Atorvastatin or Rosuvastatin seemed to benefit the most from the actions of RVX-208.”
The benefical actions of RVX-208 seen in ASSERT included significant rises in ApoA-I, the key protein in HDL, and HDL-C above baseline. This knowledge guided Resverlogix in designing SUSTAIN to reconfirm the safety of RVX-208 and utilize its action in patients with low HDL. These patients, despite statin treatment, continue to have significant CVD events. This residual risk presents a huge unmet medical need and RVX-208 is well positioned to address this care gap. According to the NHANES III study, it is estimated that nearly 35 million adults in the United States have low HDL.
“The data to be collected in SUSTAIN will further our understanding of how RVX-208 acts in a large number of patients with high residual CVD risk,” said Donald J McCaffrey, president and chief executive officer of Resverlogix. “When SUSTAIN and ASSURE are completed, we will have treated almost 1,000 patients worldwide with RVX-208. The launch of SUSTAIN reflects the confidence that we and others have in the potential for regressing atherosclerosis using RVX-208 to enhance RCT and thereby facilitate removal of cholesterol from atherosclerotic plaques to reduce CVD events.” McCaffrey added, “It is important to note that SUSTAIN will not impact Resverlogix's annual budget because the previously planned phase III tablet formulation program will be assigned lower priority thus allowing funds for SUSTAIN in the 2011/2012 budget. We expect to have data from SUSTAIN next summer.”
RVX-208 is a novel small molecule that stimulates endogenous ApoA-I production to trigger the synthesis of HDL. The use of this approach will enhance the functionality of HDL. ApoA-I is the major protein component of HDL. The main role of these particles is to act as the body's natural defense system against atherosclerosis by mediating a normal physiologic process called RCT. This pathway enables cholesterol, including that within atherosclerotic plaques of vessel walls, to be transported to the liver for further processing and elimination from the body. Enhanced RCT clearance of cholesterol from vessel walls should reduce or prevent atherosclerosis. The ability of RVX-208 to increase ApoA-I production and thereby augment RCT makes it highly differentiated from all other HDL therapies. Thus RVX-208 is positioned to be one of the most promising drugs in development for the treatment of atherosclerosis.
Resverlogix Corp. is a leading biotechnology company engaged in the development of novel therapies for important global medical markets with significant unmet medical needs.