Aeterna Zentaris Inc., an oncology and endocrinology drug development company, has announced the final phase III results for its oral ghrelin agonist, AEZS-130, which shows that the drug is safe and effective in diagnosing adult growth hormone deficiency (AGHD). Jose M Garcia, MD, PhD, of the Baylor College of Medicine and the Michael E DeBakey VA Medical Centre, presented these data at 94th ENDO annual meeting and expo recently held in Houston, Texas.
This multi-centre open label study was originally designed as a cross-over trial of AEZS-130 vs growth hormone-releasing hormone (GHRH)+L-Arginine (ARG) in AGHD patients and in controls, matched for body mass index (BMI), estrogen status, gender and age. After 43 AGHD patients and 10 controls had been tested, GHRH became unavailable. The study was completed by testing 10 more AGHD patients and 38 controls with AEZS-130 alone.
Of the 53 AGHD subjects enrolled, 52 received AEZS-130, and 50 who had confirmed AGHD prior to study entry were included in this analysis, along with 48 controls. Two AGHD subjects could not be matched due to the combination of young age, high body mass index (BMI) and estrogen use. The objective of this clinical trial was to determine the efficacy and safety of AEZS-130 in the diagnosis of AGHD.
Mean peak growth hormone (GH) levels in AGHD patients and controls following AEZS-130 administration were 2.36ng/mL (range 0.03-33) and 17.71ng/mL (range 10.5-94), respectively. The receiver operating characteristic (ROC) plot analysis yielded an optimal GH cut-point of 2.7ng/mL, with 82 per cent sensitivity, 92 per cent specificity and a 13 per cent misclassification rate. Obesity (BMI>30) was present in 58 per cent of cases and controls, and peak GH levels were inversely associated with BMI in controls.
Adverse events (AE) were seen in 37 per cent of AGHD patients and in 21 per cent of controls following AEZS 130. In contrast, 61 per cent of AGHD subjects and 30 per cent of controls experienced AEs with L ARG+GHRH. The most common AEs after AEZS-130 were unpleasant taste (19.2 per cent) and diarrhoea (3.8 per cent) for the AGHD patients and unpleasant taste (4.2 per cent) and diarrhoea (4.2 per cent) for the matched controls. AEs were generally mild or moderate in severity.
Data are available on preference of the two tests for 50 subjects. Of these, 70 per cent expressed a preference for AEZS-130 over L-ARG+GHRH.
AEZS-130, a ghrelin agonist, is a novel orally-active small molecule that stimulates the secretion of growth hormone. The Company has completed a phase III trial for use as an oral diagnostic test for AGHD. AEZS-130 has been granted orphan drug designation by the FDA for use in this indication. AEZS-130 is also in a phase II A trial as a treatment for cancer induced cachexia. Aeterna Zentaris owns the worldwide rights to AEZS-130.