AOD-9604

A 16-amino-acid synthetic peptide corresponding to the C-terminal fragment (amino acids 176–191) of human growth hormone, with a tyrosine substitution at the N-terminus and a disulfide bridge between Cys-7 and Cys-14. AOD-9604 was developed at Monash University (Prof. Frank Ng) and commercialized by Metabolic Pharmaceuticals Ltd. (Australia).

It was studied in animal models for its observed effects on lipolysis stimulation, lipogenesis inhibition, and β₃-adrenergic receptor upregulation. Unlike full-length hGH, AOD-9604 does not bind the growth hormone receptor and does not increase IGF-1 levels. Six human clinical trials (METAOD001–006) were conducted involving over 900 participants; the critical 24-week phase IIb confirmatory trial (OPTIONS/METAOD006) failed to achieve statistical significance for weight loss at any dose.

Clinical development was terminated in March 2007. AOD-9604 is not FDA-approved for any therapeutic indication.

AOD-9604 was studied in animal models showing increased fat oxidation and reduced body weight gain in obese mice and Zucker rats via β₃-adrenergic receptor upregulation. Studies in β₃-AR knockout mice confirmed the chronic weight-loss effect depends on β₃-AR signaling. Six human clinical trials were conducted: the 12-week phase IIb trial (METAOD005) showed a modest signal at 1 mg oral dose (2.8 kg vs 0.8 kg placebo), but the 24-week confirmatory trial (METAOD006/OPTIONS, 536 patients) failed to achieve statistical significance at any dose.

Development was terminated in March 2007. A rabbit osteoarthritis model later showed cartilage regeneration effects, though this has not been evaluated in humans. Dosing ranges used in community settings are extrapolated from failed clinical data and are not clinically validated.