AGHD diagnosis – macimorelin

Growth hormone is produced by the pituitary gland, and is important in maintaining healthy muscle, bone density and brain function

Growth hormone is produced by the pituitary gland. If an adult has a low level of the hormone (AGHD), they will tend to collect body fat around the waist, have abnormal triglyceride levels, less muscle and a reduction in bone density. But these symptoms can be caused by many different factors, and the withdrawal of growth hormone releasing hormone (GHRH) for diagnostic testing in the US has left diagnosis difficult.

Aeterna Zentaris’s macimorelin is an orally active ghrelin mimetic that could fill this void.1 The small molecule stimulates the secretion of growth hormone, and has been granted orphan status for the diagnostic indication. Before GHRH was withdrawn, a Phase III trial was initiated to compare the two. Initially, a total of 42 subjects with confirmed AGHD or multiple pituitary hormone deficiencies and a low insulin-like growth factor-I were given a 1µg/kg intravenous dose of GHRH with 30g of arginine over 30 minutes, or a 0.5mg/kg dose of macimorelin in an oral solution. A control group of 10 subjects without AGHD were matched to the patients for age, gender, body mass index and, for females, oestrogen status.2


After the GHRH test was no longer available, another 10 patients were tested using macimorelin, and a further 38 control patients evaluated.3 Mean peak growth hormone levels in AGHD patients and controls after the administration of macimorelin were 2.36ng/ml and 17.71ng/ml respectively. The optimal GH cut-point was established at 2.7ng/ml, with 82% sensitivity, 92% specificity and a 13% misclassification rate. Nearly 60% of the AGHD patients and controls had a BMI in excess of 30, and peak GH levels were inversely associated with BMI in the controls. Adverse events were observed in 37% of the patients and 21% of controls, including an unpleasant taste and diarrhoea, which were generally mild or moderate in severity. Sensitivity was comparable to the now-withdrawn test.

The molecule is also being investigated as a potential treatment for cancer cachexia, with a Phase IIa study having been initiated in 2012.


1. V. Guerlavais et al. J. Med. Chem. 2003, 46, 1191

2. B. Biller et al. 5th Intl Congress Growth Hormone Res. Soc. (New York, October 2010), poster presentation

3. G.R. Merriam et al. 6th Intl Congress Growth Hormone Res. Soc. (Munich, October 2012), poster presentation