Successful human trial of obesity drug that mimicks metabolic effects of growth hormone

Dec 13 2004

Metabolic Pharmaceuticals Limited today announced the success of its Phase 2b human trial of AOD9604 for obesity.

The AOD9604 molecule is a small orally active peptide modelled on one section of the human growth hormone molecule. Growth hormone naturally occurs in the body and has profound stimulatory effects on fat metabolism, with levels of the hormone typically becoming suppressed in the obese state. Daily dosing with AOD9604 restores suppressed fat metabolism in the obese by mimicking the fat metabolic effects of growth hormone.

The 300 trial subjects were comprised of men and women aged 30 to 65 years with a body mass index (or BMI, being weight in kg divided by the square of height in meters) of 35 or higher. Trial subjects received daily doses of AOD9604 or placebo in 0mg (placebo), 1mg, 5mg, 10mg, 20mg, or 30mg quantities. There were 50 subjects in each dose group. The average age of the trial participants was 44 years and their average weight was 122 kilograms (268 lbs). The trial was randomized, double blind and placebo-controlled.

The primary efficacy endpoints of the study were to determine the effect of AOD9604 on body weight reduction and/or fat reduction. The group receiving the 1mg dose lost the most weight, averaging a weight loss over the 12 weeks of 2.8 kilograms (6.2 lbs), more than triple the weight lost by those on placebo, who lost an average of 0.8 kilograms (1.8 lbs). The rate of weight loss was maintained throughout the treatment period, which is an encouraging trend for expectations of longer-term dosing.

AOD9604 also demonstrated compared to placebo a small but consistent improvement in cholesterol profiles, and a reduction in the number of patients with impaired glucose tolerance.

At all doses the drug demonstrated excellent tolerability, with no evidence for the side effects commonly experienced with existing drugs.

Prof. Louis J Aronne MD, President of the North American Association for the Study of Obesity and a member of Metabolic's Clinical Advisory Panel, said, "This is an exciting new approach to a problem which has defied easy solutions. We will need many different treatments if we are going to manage obesity successfully, in much the same way we have many treatments available for diabetes and hypertension. Unlike currently available treatments which rely on reducing calorie intake, this one appears to work primarily on metabolic pathways and merits further investigation."

"We are delighted with these results," stated Metabolic Pharmaceuticals CEO, Dr. Chris Belyea. "The evidence from the trial is that AOD9604 induces competitive weight loss at a low dose with accompanying health benefits and has superior tolerability. Our next focus is to secure a partnership with a major pharmaceutical company to assist in financing late stage longer term human clinical trials for worldwide marketing approval as a prescription treatment."

Prof. Michael Jensen MD, an expert on lipid metabolism, a past president of the North American Association for the Study of Obesity, and a member of Metabolic's US Clinical Advisory Panel, stated, "The scientific idea behind AOD9604 is an elegant one and completely different from the existing approaches to obesity. The interesting trial results reported here by Metabolic clearly justify further development and I look forward to seeing the future outcome."

Obesity is the Western World's most common health problem. Published research has indicated that more than 20% of the adult population in developed countries is obese, which is more than 300 million adults worldwide. In addition, more than 50% of adults in developed countries are overweight.