AstraZeneca is investing in a range of next generation cholesterol drugs which could reverse existing vascular disease in patients.

The Anglo-Swedish pharma giant has signed a $340 million agreement with San-Diego based biotech Avanir for a range of compounds which promise to clear arteries of the plaque which can eventually lead to heart attacks and strokes.

The novel mechanism of the drugs could represent a huge advance on current drug therapy, but the candidates are still at a very early stage, and are competing with other compounds in rival pipelines.

Current cholesterol treatments, including top-selling statins can only prevent progression of the disease and a number of companies are now in a race to launch a treatment which reverses vascular disease.

Avanir's compounds work by enhancing the body's natural reverse cholesterol transport (RCT) a complex process involving the flow of lipids from tissues, such as blood vessel walls, and their transportation to the liver for excretion.

The companies believe the compounds could shrink the plaque which lines arteries and can partially block them, leading to a heart attack or stroke.

The most advanced of the compounds will enter pre-clinical work later this year, meaning that it will be a number of years before it is ready for market.

Meanwhile, Pfizer is in a strong position to launch the first 'next generation' cholesterol drug, with torcetrapib, a novel drug which raises HDL or good cholesterol now in extensive phase III trials, but not expected to hit the market before 2008.

The company plans to combine the drug with its market leading statin Lipitor into one pill and hopes its exhaustive trials will demonstrate that raising HDL produces clinical benefits which are a clear advance over existing treatments.

The action of HDL is not entirely understood, but it is believed to transport cholesterol out of the artery wall and prevent inflammation which contributes to the blocking of arteries.

Torceptrapib is a cholesteryl ester transfer protein (CETP) inhibitor and another drug in the class, code named JTT-705 is currently in phase II development by Roche and Japan Tobacco.

Meanwhile Novartis has in-licensed a similar drug D-4F from US biotech Bruin, currently in phase I development.

The experimental nature of the research and development means the leading players have a large number of candidate molecules in the therapy area, in the hope that at least one will make it to market.

Prior to its collaboration with the biotech company AstraZeneca already had six other compounds in pre-clinical or phase I development to treat dyslipidaemia.

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Tuesday , June 28, 2005

pharmafocus@wiley.co.uk