Introduction

Coronary artery disease, stroke and other forms of cardiovascular disease (CVD) are the most significant causes of morbidity and mortality affecting men and women in the western world.  The market for CVD drugs is characterised in two areas - prevention and treatment of disease.  The Novogen cardiovascular drug program will target this market and will be entirely novel in that the drugs will have the potential to be used at an earlier stage in at-risk groups, thus reducing the burden on health resources as the population ages, as well as in symptomatic patients.  These products will be used to provide protection against cardiovascular disease in at-risk individuals as well as to prevent disease progression in patients with established conditions.  A competitive advantage will be apparent in view of the ability of these compounds to act broadly and prevent rather than simply treat cardiovascular disease and to achieve this without apparent side effects.  There are few pharmaceuticals with proven ability to achieve this objective. T here is also a clear competitive advantage over traditional standard cardiovascular therapies because of the lack of deleterious side effects, and therefore the ability to continue administration for extended periods.  While standard therapies may still be used in conjunction with these products for established conditions, the perceived preventative benefits in at-risk subjects, and the safety of their administration over long periods without apparent side effects, will ensure a broad usage and market share.

Significance of Cardiovascular Disease

It has been calculated that there is 1 death every 33 seconds in the USA from CVD and that 50,000,000 Americans have high blood pressure costing $US40 billion with drugs accounting for US$12b of this cost per year.  Women are especially at risk with a higher risk of developing CVD than men and a much higher risk of CVD than any of the other diseases women perceive as being important such as breast cancer.  Public health initiatives, mostly government funded, focus on prevention and centre around modification of diet and lifestyle, targeting known causes of CVD such as excessive fat consumption, smoking, exercise and stress reduction.

Current therapies

Public health initiatives, mostly government funded, focus on prevention and centre around modification of diet and lifestyle, targeting known causes of CVD such as excessive fat consumption, smoking, exercise and stress reduction.  Once CVD is established treatments range from drugs to modify symptoms to surgical interventions to repair or replace diseases blood vessels.  Current pharmaceutical products primarily focus on treatment when patients are symptomatic and fall into two therapeutic areas - hypertension and lipid reduction.  However none of these therapeutic approaches addresses the underlying cause of disease.

NV-04 program 

The Novogen NV-04 program has led to the development of a family of lead compounds which have potent antioxidant, antihypertensive and anti-atherosclerotic effects, targeting all of the major pathways which lead to cardiovascular disease.  Due to their natural heritage it is anticipated these will have a low toxicity and can be used over long periods of time without side effects, lending themselves to both therapeutic and preventative applications.

The pathways to CVD are shown in the illustration below.   Reduced vascular elasticity (1) leads to high blood pressure (hypertension) which can cause rupture of blood vessels (stroke); when this occurs in areas like the brain, serious physical impairment ensues.  Alternatively, thickening of the arterial wall due to atherosclerotic plaques (2) can lead to blockage of vessels and when this occurs in heart vessels a heart attack may occur.  Atherosclerosis occurs as a result of excessive deposition of LDL cholesterol (3) which is more likely to occur when HDL levels are low.  Oxidation of the LDL (4) induces an inflammatory response and the resulting lesion (5), consisting of smooth muscle cell proliferation, grows into the lumen causing reduced diameter.

In test tube and animal assays the trans NV-04 molecule has shown promise in reducing blood cholesterol, reducing LDL oxidation, reducing vascular smooth muscle cell proliferation, and improving vascular elasticity.