Powerful effects seen in all subjects including those with low HDL - representing a majority of myocardial infarct patients TSX Exchange Symbol: RVX
CALGARY, Sept. 29 /PRNewswire-FirstCall/ - Resverlogix Corp. ("Resverlogix" or the "Company") (TSX:RVX) announced today that results from the Company's Phase 1b/2a clinical trial have met and exceeded expectations by successfully concluding the drug, RVX-208, is safe and tolerable. Most importantly RVX-208 has met its primary endpoint to increase the production of plasma ApoA-I, the key cardioprotective protein in high-density lipoprotein (HDL), often referred to as "good" cholesterol. ApoA-I is generally endorsed as a key protective factor against atherosclerosis and cardiovascular disease with 40% of all first heart attack patients having low ApoA-I.
Resverlogix's Phase 1b/2a study tested RVX-208 for 28 days in three different dosing arms. The most pronounced results were demonstrated among those subjects with low HDL cholesterol levels. Low HDL is an important risk factor in coronary and cardiovascular disease patients. Resverlogix will continue to build upon its world leading position in development of novel small molecules that increase ApoA-l production and reverse cholesterol transport (RCT) markers in patients with high vascular risk profiles. RCT is a path by which cholesterol on the arterial wall is transported back to the liver by ApoA-I lipid complexes for excretion. Additional analysis was performed on other key RCT markers which achieved high levels of statistical significance. The Company has established a dosing range that it deems will be safe, well tolerated and effective for Phase 2 intravascular ultrasound (IVUS) development trials.
"The range of increase in ApoA-l production of all subjects, but in particular low HDL subjects over placebo demonstrated in this study is one of the most significant pieces of data for RVX-208. We have exceeded our original expectation for enhancing ApoA-l production in humans," stated Donald J. McCaffrey, President and CEO of Resverlogix. "We know that the enhancement of ApoA-l and key RCT particles in the body is widely recognized by international experts as the necessary markers to potentially impact atherosclerosis regression. Hence, we have achieved another critically important clinical milestone for our Company," noted McCaffrey.
The Phase 1b/2a trial was a double blind safety and tolerance study which investigated the pharmacokinetics and also early pharmacodynamics effects of RVX-208. A total of 72 subjects enrolled in the trial. The study had three arms, a low dose arm with 24 subjects, a dose-escalation arm with 24 subjects, and a third high dose arm with 24 subjects. This trial also examined early markers for reverse cholesterol transport such as ApoA-l, HDL-c, pre-beta HDL and alpha HDL subparticles. Approximately half of the subjects had low levels of baseline HDL cholesterol.
Highlights from the study are as follows:
- The primary endpoint, plasma ApoA-I increase compared to placebo, achieved a range in all subjects of 5.1% - 10.4% in all doses at days 8 and 28 respectively. - At the lowest dose of 1mg/kg b.i.d. in subjects with low levels of HDL-c, plasma ApoA-l increases reached statistical significance of 5.7% (p(less than)0.05) at day 8 and 7.8% (p(less than)0.05) at day 28. - A critical RCT functionality marker, alpha-1 HDL particles, illustrated highly statistical significance with an increase of 46.7% (p(less than)0.004), in all subjects and 57.2% (p(less than)0.02) in the low dose arm over placebo at day 28. - Pharmacokinetic parameters of RVX-208 were dose dependant with oral administration. - RVX-208 was shown to be compatible with simvastatin (40mg). - Seventy out of seventy two subjects completed the trial. One subject did not complete the trial due to personal reasons and one other subject did not complete the trial due to a serious adverse event, cholecystitis (gall stones), which was judged not related to the study drug.
Based on these important findings, the Company now plans to adjust its future dosing. Expanded Phase 2 planning is moving forward to include Phase 2 IVUS trials, a Phase 2 dosing trial and a Phase 2 combination statin trial. The IVUS Steering Committee is chaired by Dr. Steven Nissen, Chairman of the Cleveland Clinic Department of Cardiovascular Medicine, and the principal investigator is Dr. Stephen Nicholls, Medical Director of Intravascular Ultrasound at Cleveland Clinic.
"The results we have observed in our second clinical trial illustrate an important emerging pattern of predictability. To date 162 human subjects have received RVX-208 which has consistently demonstrated itself to be a well tolerated and safe therapeutic," stated Dr. Jan Johansson Senior Vice President of Medical Affairs at Resverlogix. "It is important to note that in addition to the increases in ApoA-I and HDL, we also saw very pronounced increases in alpha-1 HDL, another important marker for CVD risk. The landmark Framingham Offspring Study clearly illustrated that among HDL and LDL, alpha-1 HDL was a more critically important marker for CVD protection," Dr. Johansson added.
Developing small molecules that increase ApoA-I would satisfy a huge unmet medical need because CVD treatment with statins, the current standard of care, only stabilizes atherosclerosis and reduces cardiovascular risk by 30%. A recent cost-benefit pharmacoeconomic analysis of ApoA-I therapy for CVD estimated that a 1% and 5% regression of atherosclerosis would save the U.S. health care system and employers between US $22.9 billion and US $76.8 billion annually over and above statin therapy. The analysis assumes ApoA-I therapy will be given to CVD patients in combination with statins. ApoA-I therapy has the potential to reduce the overall cost of cardiovascular disease, which is estimated in the U.S. at US $475 billion annually, by 5% to 16%.
Resverlogix is also pleased to announce that it will host a live teleconference today, September 29, 2009 at 1:00 pm Eastern/11:00 am Mountain time. The purpose of the teleconference is to discuss the top line results of this clinical trial. The dial-in numbers for this event are toll free 1-800-319-4610 and international 1-604-638-5340. A link for this webcast is posted onto the homepage of Resverlogix's website and can be accessed from the following address http://services.choruscall.com/links/resverlogix090928.html. The webcast will be available on the Resverlogix website for replay for a period of 45 days after the event.
RVX-208, a novel small molecule therapeutic that facilitates endogenous ApoA-I production, is positioned to be one of the most promising emerging drugs in the treatment of atherosclerosis. To the Company's knowledge RVX-208 is the only novel small molecule that is specifically designed to increase ApoA-I production and thereby raise HDL levels thus enhancing HDL functionality to augment reverse cholesterol transport (RCT). RCT is a pathway by which accumulated cholesterol is transported from the arterial wall to the liver for excretion, thus preventing atherosclerosis.
About Resverlogix Corp.
Resverlogix Corp. is a leading biotechnology company engaged in the development of novel therapies for important global medical markets with significant unmet needs. The NexVas(TM) PR program is the Company's primary focus which is to develop novel small molecules that enhance ApoA-I. These vital therapies address the grievous burden of atherosclerosis and other important diseases such as Acute Coronary Syndrome, Diabetes, Alzheimer's disease, Peripheral Artery Disease and other vascular disorders. Resverlogix Corp. trades on the Toronto Stock Exchange (TSX:RVX). For further information please visit www.resverlogix.com.
This news release may contain certain forward-looking statements that reflect the current views and/or expectations of Resverlogix Corp. with respect to its performance, business and future events. Such statements are subject to a number of risks, uncertainties and assumptions. Actual results and events may vary significantly. The TSX Exchange does not accept responsibility for the adequacy or accuracy of this news release.
SOURCE Resverlogix Corp.
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