Phosphagenics Reports Superior Pre Clinical Cholesterol Results From APA 01 And Atorvastatin Combination

Main Category: Cardiovascular / Cardiology
Also Included In: Statins;  Clinical Trials / Drug Trials;  Pharma Industry / Biotech Industry
Article Date: 31 Jan 2008 - 0:00 PST

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Phosphagenics Limited ("Phosphagenics") (ASX: POH, AIM: PSG, OTCQX: PPGNY) announced results of a pre-clinical study demonstrating that the combination of its APA- 01 product candidate and the statin atorvastatin (Lipitor(TM)) significantly reduced serum lipids and inflammatory proteins involved in the development of atherosclerosis.

Study Design

The purpose of the study was to determine whether a combination of the statin drug atorvastatin and APA-01 could reduce serum lipids, inhibit atherosclerotic lesion progression and reduce proinflammatory cytokines and other biomarkers of inflammatory disease more effectively than the statin alone.

Studies were performed in ApoE mice, animals that spontaneously form atherosclerotic plaques and represent a well-established model of human atherogenic hyperchosterolemia.

During the first 16-weeks of this 24-week study, all animals in the experimental group were maintained on a standard diet, followed by an eight week treatment period in which this diet was supplemented with 21% fat and 0.15% cholesterol, an atherogenic diet expected to accelerate atherosclerotic progression. All animals in the experimental groups received drug treatment in both their normal and high-fat diets at various dosing regiments throughout the 24-week study. Control group animals received no drug treatment and were maintained on either the same diet as the treatment groups or on a standard diet.

Study Results

Effects on Serum Lipids

The study results indicated that among the animals treated with the APA-01 and atorvastatin combination, total cholesterol levels fell by up to an additional 12% compared to those animals treated with atorvastatin alone. Total HDL-C (good cholesterol) levels increased by up to 37% in combination drug-treated animals, while LDL-C (bad cholesterol) levels were further reduced by up to 24% with the combination, as opposed to atorvastatin alone. The combination also caused a decrease of 92% in triglycerides levels compared to 72% with atorvastatin alone.

Effects on Biomarkers of Inflammation

APA-01, combined with atorvastatin, enhanced the statin's effects on lowering inflammation that contributes to the development of atherosclerotic plaques. Reductions occurred in final plasma levels of 23 cytokines that were measured. Following 24 weeks of treatment with various doses of APA-01 and atorvastatin, a statistically significant reduction occurred in a number of cytokines including IL-1B, IL-10, G-CSF, GM-CSF, IFN-y, MCP-1, and RANTES compared to control and these decreases were greater than with either compound alone and appeared to be somewhat dose-dependent.

Effects on Atherosclerotic Plaque Progression

Atherosclerotic lesions were significantly elevated following incorporation of the high-fat high-cholesterol diet in all animals compared to animals maintained on the regular, rodent diet for the 24-week study period. The effect of the combination treatment of APA-01 combined with atorvastatin appeared to cause a trend toward decreased aortic lesions, but these were not statistically significant.

Commenting on the study results, Dr. Esra Ogru, Executive Vice President of Research and Development at Phosphagenics, said, "Current therapies for atherosclerosis focus on drugs that lower serum cholesterol levels. Experimental and clinical evidence suggests that the efficacy of these drugs may also be related to their ability to reduce oxidative stress and inflammation in the endothelium, or blood vessel lining, where atherosclerotic plaques develop. We believe that APA-01's apparent enhancement of a statin's anti-inflammatory functions could potentially provide a novel therapeutic approach to treating atherosclerosis."

Atorvastatin is the world's largest selling drug with sales of US$13.6 billion annually and is the primary contributor to the US$35.2 billion market for statin drugs globally.

"In particular there is an unmet need for a more effective treatment for elevated triglycerides and APA-01 has demonstrated efficacy in this area in this preclinical study. We are now assessing the impact of these results before determining our future strategy. However, the insulin, oxycodone and Phospha E(R) clinical programs will remain our priority for this year," Dr. Ogru said.

About Atherosclerosis

Atherosclerosis, or the build-up of fatty deposits (plaques) on interior blood vessel walls, is a progressive process initially involving endothelial dysfunction and accumulation of lipids on the linings of blood vessel. Atherosclerotic lesions develop as a result of inflammatory stimuli, subsequent release of various cytokines, proliferation of smooth muscle cells, synthesis of connective tissue matrix, and accumulation of macrophages and lipids. Atherosclerosis is involved in the development of coronary heart disease, myocardial infarction, and stroke, among other diseases.

About Phosphagenics Limited

Phosphagenics is a Melbourne-based, globally driven biotechnology company focused on the discovery of new and cost effective ways to enhance the bioavailability, activity, safety and delivery of proven pharmaceutical and nutraceutical products.

Phosphagenics' core technology is built around the science and application of phosphorylation, a process where the addition of a phosphate group has been found to enhance the bioavailability, activity and safety of existing pharmaceuticals and nutraceuticals, as well as to assist in the production of drug delivery platforms.

Phosphagenics' shares are listed on the Australian Stock Exchange (POH) and the London Stock Exchange's Alternative Investment Market (PSG). An ADR -- Level 1 program was established in the U.S. with The Bank of New York Mellon (PPGNY) for U.S. investors to trade in Phosphagenics' stock on the 'over-the- counter' market. In July 2007, this was upgraded to the International OTCQX, a new premium market tier in the U.S. for international exchange-listed companies, operated by Pink Sheets, LLC.

For more information, please visit Phosphagenics' web site at http://www.phosphagenics.com.

Safe Harbor Statement

This press release contains forward-looking statements based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialise, actual results could vary materially from the Phosphagenics' expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations.

Phosphagenics Limited
http://www.phosphagenics.com

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