Novogen claims success in heart drug trial

Sydney pharmaceutical company Novogen (ASX:NRT, NASDAQ:NVGN) says the first human clinical trial of its candidate heart-disease therapeutic NV-04 has confirmed the "outstanding potency" it showed in initial trials in laboratory animals.

In the Phase I trial at the Baker Medical Research Institute in Melbourne, six healthy volunteers with no history of cardiovascular disease were injected with the drug to test its efficacy and safety.

Dr Jaye Chin-Dusting, head of the Baker's vascular pharmacology laboratory, which conducted the independent trial, said all six patients experienced significant increased arterial blood flow.

The earlier animal trials, conducted in the same laboratory, showed that NV-04 induced relaxation in the smooth muscle of the vascular endothelium, the elastic lining that allows artery walls to constrict and dilate.

When arteries dilate, resistance to blood flow falls, in turn reducing blood pressure. If atherosclerosis reduces the diameter of an artery only by half - the reduction may be even greater in patients with severe atherosclerosis - resistance to blood flow can increase by 16-fold.

Atherosclerosis, or the accumulation of fatty atherosclerotic plaque in major arteries, is a major causes of ill health and early death in affluent Western nations - in the US alone, annual expenditures on cardiovascular drugs are estimated at $US17.7 billion.

As blood flow through the constricted arteries is reduced, the heart must work harder to pump blood round the body, even as its own blood supply is reduced by plaque build-up in the vital arteries carrying its own blood supply.

Dr Chin-Dusting said the results in the six human patients were consistent with the animal trial results, which showed that compounds in the NV-04 program relaxed and dilated the arteries, act as antioxidants that inhibit the build-up of atherosclerotic plaque, and inhibit the growth of smooth-muscle cells in blood vessels, all of which contribute to an increased risk of heart attack and stroke.

Dr Chin-Dusting said the Baker team would submit its results for publication in a key medical journal as soon as possible.

Low toxicity

Novogen's research director, Prof Alan Husband, said the fact that the same effects observed in laboratory animals had now been observed in human patients was "a particularly exciting outcome."

NV-04 has exhibited very low toxicity in laboratory animals, and Husband said it was expected to be sufficiently safe to administer over long periods to humans without side-effects.

Novogen director Dr Graham Kelly said that, like all other Novogen therapeutics already on the market, or under development, NV-04 was an analogue, or mimic, of a class of plant-derived compounds called isoflavones, which, among other things, were potent natural antioxidants.

NV-04 is an analogue of genistein, a naturally occurring compound in soybeans, which research has shown produces a range of potential benefits for the prevention and treatment of cardiovascular disease.

Kelly said animal trials indicated that NV-04, synthesised by Novogen's chemists, was even more potent than genistein, which was shown to prevent re-stenosis in monkeys after angioplasty to widen narrowed arteries.

Genistein has also been found to have antioxidant and anti-inflammatory actions, preventing the cells of the vascular endothelium becoming irritated by oxidised low-density lipoproteins - so-called "bad cholesterol".

Not only does genistein inhibit the inflammatory process that causes plaque build-up, it actually reverses it by inducing apoptosis - programmed cell suicide - of the swollen cells that narrow and block arteries.

Genistein's third mode of action, its ability to relax and dilate narrowed arteries, is due to its ability to inhibit the synthesis of nitric oxide, the compound that causes arteries to constrict.

The first clinical trial suggests that Novogen's NV-04 genistein analogue is at least as potent as genistein itself in replicating these therapeutic effects.

Novogen managing director Christopher Naughton said the company would now move rapidly to conduct Phase I trials of an oral formulation of NV-04 in human patients.

Record cash reserves

Novogen last week announced that it had ended the 2001-02 year with record cash reserves - $40 million, compared with $31 million for the previous financial year.

It claimed the good result was due to stringent cost-control measures, and the successful listing and financing of Novogen's 95.2 per cent owned US subsidiary, Marshall Edwards, Inc on the London Stock Exchange's Alternative Investment market, which raised $18.7 million from European and US private investors.

The increase accompanied a 33 per cent reduction in Novogen's net loss for the 12 months, down from $A21.7 million to $A14.6 million.

At a ceremony in Sydney on Monday night, NSW Minister for State Development Michael Egan presented Novogen with an Australian Technology Showcase Patron's Award for outstanding achievement in international markets, in recognition of the success of the company's post-menopause dietary therapeutic Rimostil.