History and Devel­op­ment

The story of AOD-9604 starts in an Australian university laboratory, passes through a decade of company-funded trials and ends, as a drug candidate, with a disappointing result in 2007.

Early Work at Monash

Frank Ng and colleagues at Monash University had long studied how growth hormone affects fat. In 1993 they reported that a synthetic copy of the hormone's 177 to 191 region slowed fat production in rat tissue. A year later, in genetically obese mice, the same fragment reduced weight gain and fat mass. The modified version with an extra tyrosine became known as AOD-9604.

A Company Takes Over

Metabolic Pharmaceuticals, a Melbourne biotech company, developed the peptide as a possible obesity treatment. Studies published in 2000 and 2001 showed that it worked in obese rats when given by mouth, and that obese mice treated for two weeks put on less weight and burned more fat, without high blood sugar.

Human Trials, 2001 to 2007

Six randomised, placebo-controlled trials followed, involving roughly 900 adults in total. They started with single doses given into a vein or by mouth and moved on to a 7-day study, a 12-week study with about 300 people and finally a 24-week study run at 16 Australian sites. In the 12-week trial, the 1 mg group was reported to lose 2.6 kg compared with 0.8 kg on placebo, which encouraged the company to continue.

The 2007 Result

The 24-week study, called OPTIONS, enrolled 536 people with obesity and compared three daily tablet strengths with placebo. In February 2007 Metabolic announced that none of the groups had lost significantly more weight than the placebo group. The company stopped developing AOD-9604 for obesity, and its share price fell by more than 70%.

A Second Life

A combined safety analysis of all six trials was published in 2013 and found the tablet well tolerated. In the years after, the peptide drew interest for joint research, appeared in seized products tested by anti-doping laboratories, and was named by WADA in a 2013 statement. In the United States the FDA reviewed it for pharmacy compounding between 2023 and 2024 and did not add it to the permitted lists.