New drug chews the fat for Metabolic

Metabolic has just completed Phase IIA studies in a group of 22 clinically obese, but otherwise healthy, male patients ranging in age from 22?50. The results showed that the drug was well tolerated and increased fat metabolism within two hours of administration by 25 per cent in the older group of patients. Although not the focus of the study, weight loss was also demonstrated, particularly in the older group.

Advanced Obesity Drug 9604 (AOD9604), targets fat metabolism directly by enhancing the breakdown of stored fats and inhibiting the synthesis of new fats. It is a peptide drug derived from the fat-reducing activity of human growth hormone (hGH). hGH has been shown to cause fat reduction, but is not suitable as an anti-obesity drug as it also causes an increase in muscle, organ and bone mass as well as causing diabetes to develop. The effectiveness of hGH declines in older people, correlating with the tendency to put on weight as one gets older. In support of this, the clinical trials so far have shown a greater effect of AOD9604 in the older population.

Metabolic managing director Dr Chris Belyea said AOD9604 was one of the few drugs in development that acted on fat metabolism instead of suppressing appetite or inhibiting fat digestive mechanisms.

"A doctor is much more likely to prescribe a drug that addresses the underlying metabolic problem," Dr Belyea said. In addition, all of the drugs currently on the market have noticeable side-effects ranging from mood changes to unpleasant effects on the digestive system. The FDA withdrew fenfluramine and dexfenfluramine (Redux), from the market in 1997 after the drugs were linked to heart valve abnormalities.

Obesity affects as many as one in five adults in developed countries. Metabolic estimates that the potential worldwide market for effective obesity drugs is as much as $20 billion, far more than the current market of $1.5 billion. This is partly due to the potential need for chronically obese people to take obesity drugs such as AOD9604 and also because patients are put off using currently available drugs because of their marginal efficacy or side-effects.

Metabolic plans to develop AOD9604 itself, rather than license it to a larger company. "Big pharmaceutical companies are good for marketing, but not as good for development," Dr Belyea said. "We are keeping our options open at this point."

Meanwhile, more Phase II clinical studies are planned for the next 12 months including a study examining the efficacy of oral administration, which has been shown to be effective in laboratory animals. This will be followed by a weight loss study. Confirmation of the age-effect will also be sought. Metabolic aims to start a two-year Phase III studies program in 2003, which would not place final FDA approval before 2005.

AOD9604 is currently being produced by chemical synthesis under contract, but a method of producing the peptide drug as a transgene in plants is also under consideration, in collaboration with SemBioSys, a Canadian biotechnology company.

Dr Belyea said the new method was promising, and had several economic advantages over chemical synthesis or fermentation production methods. The drug would be produced in the seed of the plant and easily purified. Dr Belyea said the drug may eventually be available as a nutraceutical product.

AOD9604 also has veterinary applications as a food additive in the livestock industry, particularly for pigs. Growth hormone is already used to produce leaner pigs, and AOD9604 may provide a suitable substitute with the advantage of being an oral product.

Metabolic is also developing drugs for type 2 diabetes and is examining other potential products. The company was listed on the Australian Stock Exchange (ASX: MBP) in November 1998. Its stock price has risen from $0.39 in mid-September 2001 to $0.97 on February 4. Its major shareholder is Circadian Technologies (ASX: CIR).