Victory elusive in fight against flab

A pill to stop you getting fat is an enticing prospect for couch potatoes and drug companies alike.

Obesity affects more than 300 million people around the world. It is the Western world's fastest-growing health problem and one of the hottest areas of pharmaceutical research.

But despite the multibillion-dollar prize, producing effective treatments for a condition that can cause diabetes and heart disease is proving a long, difficult and risky business.

Abbott Laboratories became the latest firm to hit trouble when its Reductil drug was withdrawn in Italy on safety grounds last month and the consumer group Public Citizen called for a ban in the United States, where the drug is sold as Meridia.

Critics link the drug to at least 33 deaths in the US and Europe. Abbott says there is no evidence to connect its product with the deaths and insists it is safe.

The row has done nothing to reassure doctors and patients about an area of therapy littered with past failures.

They include the 1997 recall of two drugs linked to heart problems used in a slimming cocktail known as "fen-phen" and taken by six million Americans.

American Home Products, since renamed Wyeth, is only now recovering from the fallout, having been forced to take a record $US13.2 billion ($29.8 billion) in charges for liabilities.

Today, there are just two major obesity medicines on the market - Meridia/Reductil, which suppresses appetite, and Roche Holding AG's Xenical, which limits fat absorption.

In both cases, the weight loss benefits are modest and Xenical comes with some unpleasant side-effects, such as diarrhoea after a high-fat meal.

Sales of the two drugs, as a result, have been slow. Xenical, once flagged as the main hope for Swiss drugmaker Roche, raked in 963 million Swiss francs ($1.30 billion) last year and Abbott's drug sold $US202 million ($456.25 million) - relatively small beer in a global drugs industry of $US350 billion ($790.5 billion) a year.

But despite a rocky past, obesity remains a priority area for research in pharmaceutical laboratories in Europe, the US and Japan.

Jonathan de Pass, who heads the London-based drugs consultancy Evaluate, counts more than 30 anti-obesity drugs in development and many more at the early research stage.

A number of new approaches are being adopted in the fight against flab - but the jury is still out on whether their benefits will outweigh the inevitable side-effects.

Much research effort has gone into a class of drugs known as beta-3 agonists, designed to encourage the body to burn more energy without additional physical exertion.

Leading drug companies including Pfizer, GlaxoSmithKline, Merck and Bristol-Myers have all been working on beta-3 products but have yet to find the perfect molecule that does not over-stimulate the heart and cause cardiovascular problems.

The French firm Sanofi-Synthelabo has taken a different tack by designing a drug which turns off the biological "switch" in the human brain that makes people hungry when they smoke cannabis.

The so-called cannabinoid receptor antagonist, known by the codename SR141716, is in final Phase 3 studies, after demonstrating significant weight reduction in early tests.

Other unusual drug candidates include a product, P57, derived from a rare cactus which British plant-based drug firm Phytopharm has licensed to Pfizer.

It is now in Phase 2 trials and, if successful, will earn a windfall profit for the Kalahari bushmen. who have been using the hoodia plant to stave off hunger for thousands of years.

The new science of genomics - understanding the links between genes and disease - is also being brought to bear on obesity.

The US group Millennium Pharmaceuticals is working with Abbott on the first such genomics-derived product.

Millennium's drug, which started to be tested on people in November, works by blocking an enzyme called carboxypeptidase that encourages the body to store fat. Inhibiting its action should prompt patients to burn fat instead.

Scientists do not expect to find a "smoking gun" in the form of a single gene that causes obesity.

But by studying how genes differ in people who are overweight, Millennium and rivals such as Iceland's deCODE Genetics believe they can tease out new leads for treatment, although drugs based on this knowledge are many years away.

- REUTERS

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