Rosebud
Sat, Dec-24-05, 15:27
http://www.smh.com.au/news/world/a-pill-to-shrink-the-masses/2005/12/23/1135032186820.html
A pill to shrink the masses
December 24, 2005
One company stands to make billions from a drug that could reduce obesity, writes Diane Martindale.
IT STARTED with a joint. Back in the 1960s, psychologists studying the effects of cannabis on short-term memory noticed the subjects couldn't keep their hands off the free marshmallows. What the researchers were seeing was confirmation of a well-known side effect of smoking cannabis - intense hunger pangs known as the munchies.
Fast-forward 40 years, and scientists are talking about the munchies again, albeit in a different way. Early next year, the French pharmaceutical company Sanofi-Aventis will start selling a drug designed to induce the "anti-munchies". Rimonabant taps into the same brain circuits as cannabis, but instead of turning them on, it turns them off. If what has been made public from the clinical trials is anything to go by, Rimonabant has almost miraculous powers, helping people to control their appetites and banish many of the metabolic problems associated with being too fat.
And that's not all. Rimonabant could possibly be a quit-smoking aid and might even be useful in treating alcoholism and other addictions. No wonder many industry analysts are backing it to become the first blockbuster drug of the 21st century.
But some are yet to be convinced. They agree that the available results look promising, but point out that there has been only one peer-reviewed article from the clinical trials. And although the drug's reported side effects are minor, nothing is known about potential long-term effects.
In 1988, researchers at the St Louis University School of Medicine in Missouri discovered the active ingredient of cannabis exerts its effects by binding to specific receptors in the brain. These cannabinoid receptors, or CB1s, turned out to be part of a network throughout the brain and body whose main role is to damp down the activity of other signalling systems.
Researchers have discovered that this "endocannabinoid" system is involved in all kinds of functions, including memory, nausea, pain, reproduction and immunity. It also plays a part in appetite and fat storage.
The details are unclear, but animal studies suggest that cannabis-like molecules produced in the body bind to CB1 receptors on neurons in the hypothalamus, the brain's main control centre for food intake. In doing so, the molecules inhibit other signals that tell us not to eat, and make us feel hungry. Rimonabant blocks CB1 receptors, which appears to reduce the hunger.
In the 1990s, Sanofi-Avenist - then Sanofi-Synthelabo - recruited 6600 overweight or obese people into four clinical trials to test Rimonabant and another 6500 volunteers in smoking cessation trials. All four obesity trials are complete. Sanofi-Avenist has published only one set of results, in the April 16 issue this year of The Lancet, from the halfway point of a two-year European study of 1507 volunteers.
All the volunteers were put on a calorie-restricted diet and an exercise program, plus a daily dose of either a placebo or a low or high dose (5 or 20 milligrams) of Rimonabant. Those on the placebo shed an average of 1.8 kilograms and saw their waists shrink by 2.4 centimetres. But those on a high dose of Rimonabant lost an average of 6.6 kilograms and reduced their waist size by 6.5 centimetres. More than two-thirds of this group had lost 5 per cent or more of their body weight.
And there was a big drop in the proportion who had "metabolic syndrome" - a cluster of symptoms associated with obesity, including lipid imbalance, high blood pressure and insulin resistance, which can lead to heart disease and diabetes. The number with the syndrome fell from about 42 per cent to 20 per cent in the high-dose group, compared with a fall from 40 to 31 per cent in the placebo group.
The researchers who analysed the results, led by Luc Van Gaal of Antwerp University Hospital in Belgium, found the improvements in metabolic benefit were better than could be expected from the weight loss alone.
As for the smoking cessation trials, so far the company has only released the results of a 10-week trial involving 787 people, but these look promising.
Sanofi-Aventis submitted its results to the US Food and Drug Administration and the European Medicines Agency earlier this year. If it gets the go-ahead, Rimonabant will sell as Acomplia. The investment bank JP Morgan predicts sales will reach 5 billion a year by 2010.
Curiously, however, Sanofi-Aventis does not intend to market Rimonabant for weight loss or smoking cessation, preferring to cast it as a heart medication on the back of the cardiovascular benefits of curbing metabolic syndrome and giving up cigarettes. This could make good business sense, since US health insurance companies rarely pay for anti-obesity drugs but will cover cardiovascular medication. And the regulatory agencies tend to be extra critical of weight-loss medications.
New Scientist
A pill to shrink the masses
December 24, 2005
One company stands to make billions from a drug that could reduce obesity, writes Diane Martindale.
IT STARTED with a joint. Back in the 1960s, psychologists studying the effects of cannabis on short-term memory noticed the subjects couldn't keep their hands off the free marshmallows. What the researchers were seeing was confirmation of a well-known side effect of smoking cannabis - intense hunger pangs known as the munchies.
Fast-forward 40 years, and scientists are talking about the munchies again, albeit in a different way. Early next year, the French pharmaceutical company Sanofi-Aventis will start selling a drug designed to induce the "anti-munchies". Rimonabant taps into the same brain circuits as cannabis, but instead of turning them on, it turns them off. If what has been made public from the clinical trials is anything to go by, Rimonabant has almost miraculous powers, helping people to control their appetites and banish many of the metabolic problems associated with being too fat.
And that's not all. Rimonabant could possibly be a quit-smoking aid and might even be useful in treating alcoholism and other addictions. No wonder many industry analysts are backing it to become the first blockbuster drug of the 21st century.
But some are yet to be convinced. They agree that the available results look promising, but point out that there has been only one peer-reviewed article from the clinical trials. And although the drug's reported side effects are minor, nothing is known about potential long-term effects.
In 1988, researchers at the St Louis University School of Medicine in Missouri discovered the active ingredient of cannabis exerts its effects by binding to specific receptors in the brain. These cannabinoid receptors, or CB1s, turned out to be part of a network throughout the brain and body whose main role is to damp down the activity of other signalling systems.
Researchers have discovered that this "endocannabinoid" system is involved in all kinds of functions, including memory, nausea, pain, reproduction and immunity. It also plays a part in appetite and fat storage.
The details are unclear, but animal studies suggest that cannabis-like molecules produced in the body bind to CB1 receptors on neurons in the hypothalamus, the brain's main control centre for food intake. In doing so, the molecules inhibit other signals that tell us not to eat, and make us feel hungry. Rimonabant blocks CB1 receptors, which appears to reduce the hunger.
In the 1990s, Sanofi-Avenist - then Sanofi-Synthelabo - recruited 6600 overweight or obese people into four clinical trials to test Rimonabant and another 6500 volunteers in smoking cessation trials. All four obesity trials are complete. Sanofi-Avenist has published only one set of results, in the April 16 issue this year of The Lancet, from the halfway point of a two-year European study of 1507 volunteers.
All the volunteers were put on a calorie-restricted diet and an exercise program, plus a daily dose of either a placebo or a low or high dose (5 or 20 milligrams) of Rimonabant. Those on the placebo shed an average of 1.8 kilograms and saw their waists shrink by 2.4 centimetres. But those on a high dose of Rimonabant lost an average of 6.6 kilograms and reduced their waist size by 6.5 centimetres. More than two-thirds of this group had lost 5 per cent or more of their body weight.
And there was a big drop in the proportion who had "metabolic syndrome" - a cluster of symptoms associated with obesity, including lipid imbalance, high blood pressure and insulin resistance, which can lead to heart disease and diabetes. The number with the syndrome fell from about 42 per cent to 20 per cent in the high-dose group, compared with a fall from 40 to 31 per cent in the placebo group.
The researchers who analysed the results, led by Luc Van Gaal of Antwerp University Hospital in Belgium, found the improvements in metabolic benefit were better than could be expected from the weight loss alone.
As for the smoking cessation trials, so far the company has only released the results of a 10-week trial involving 787 people, but these look promising.
Sanofi-Aventis submitted its results to the US Food and Drug Administration and the European Medicines Agency earlier this year. If it gets the go-ahead, Rimonabant will sell as Acomplia. The investment bank JP Morgan predicts sales will reach 5 billion a year by 2010.
Curiously, however, Sanofi-Aventis does not intend to market Rimonabant for weight loss or smoking cessation, preferring to cast it as a heart medication on the back of the cardiovascular benefits of curbing metabolic syndrome and giving up cigarettes. This could make good business sense, since US health insurance companies rarely pay for anti-obesity drugs but will cover cardiovascular medication. And the regulatory agencies tend to be extra critical of weight-loss medications.
New Scientist