Background: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by hyperphagia and abnormal behaviours towards food for both of which no approved treatment is available. Elevated plasma acylated ghrelin (AG) documented at all ages in PWS suggest that the ghrelin system may contribute to the pathophysiology of hyperphagia. Administration of unacylated ghrelin and 8-amino acid analog AZP-531 prevents AG-induced food consumption in animals and improves glucose control and decreases weight in animal models and in Phase 1 clinical trials.
Objective and hypotheses: To evaluate the safety, tolerability and effects of AZP-531 on food-related behavior in patients with PWS.
Method: About 47 male and female patients with PWS and evidence of hyperphagia (mean age: 26.8±6.7 yrs, range: [1346 yrs], mean BMI: 38.00±12.01 kg/m2, range: [20.667.4 kg/m2]) were randomly assigned to receive sc AZP-531 (3 mg or 4 mg) or placebo once daily for 14 days. Study assessments were performed on Day -1 (baseline), Day 1 and Day 14.
Results: AZP-531 was well tolerated. A significant improvement in food-related behavior, as assessed by the Hyperphagia questionnaire, was noted in AZP-531 patients on Day 14 (P<0.05 vs placebo) with particular improvement in the severity score (P<0.05 vs placebo). Findings were supported by reduction in appetite feelings following breakfast. Body weight did not change after treatment with AZP-531 for 2 weeks in this highly variable population at baseline but waist circumference decreased (P<0.05 vs baseline) and glucose control tended to improve with a greater effects in patients with higher fasting or post-prandrial glucose levels at baseline.
Conclusion: AZP-531 may be a new treatment strategy for PWS. Data support further investigation to assess long-term safety and efficacy on food-related behaviour and metabolic parameters.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology