Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans

Stier H, Vos E, Kenley D · Journal of Endocrinology and Metabolism

A sponsor-authored summary of the safety data from the six trials, which pools no effect estimates and reports no weight-loss result. Serum IGF-1 did not change against placebo in either long-term trial (change from baseline minus 0.18 to plus 1.28 nmol/L across the 1 to 30 mg groups at 12 weeks, none significant; p equal to 0.51 and 0.76 at 12 and 24 weeks in the 502-patient trial), oral glucose tolerance did not deteriorate, no anti-AOD9604 antibodies were found, and no withdrawal or serious adverse event was attributed to the drug. Headache and gastrointestinal complaints were the commonest events and were more frequent at 54 mg. Five cancers arose in the 12-week trial, all in AOD9604 arms (three skin cancers and a lipoma at 20 mg, a breast cancer at 5 mg, a melanoma at 10 mg), which the investigator judged unrelated because none was in the highest-dose group.

Population

Six sponsor-run, double-blind, placebo-controlled trials in Australia between 2001 and 2006: two single-dose intravenous studies in 15 healthy and 23 obese men, two oral studies in 17 and 36 obese men, and two oral phase 2b trials in 300 and 502 obese adults for 12 and 24 weeks

Intervention

AOD9604 intravenously at 25 to 400 µg/kg, or orally at 0.25 mg to 54 mg a day

Comparator

Placebo; one intravenous study also gave recombinant growth hormone as a positive control

Limitations

Written by a consultant to the sponsor with the sponsor's medical director and its chief executive as co-authors, from trial reports that have not themselves been published; Metabolic Pharmaceuticals funded all six trials. It is a narrative safety summary rather than a meta-analysis, and it says nothing about whether the drug reduced weight, which the same sponsor's 2014 paper concedes it did not in the last trial. The attribution of five cancers to chance rests on a dose argument and on the participants' medical histories rather than on any comparison with the placebo arm.