Results from the randomized, double blind and placebo-controlled Phase II trial show significant improvements in hyperphagia-related behavior, a key therapeutic objective in Prader-Willi Syndrome.
Alizé Pharma SAS, an Alizé Pharma group company specialized in the development of biopharmaceuticals to treat metabolic disorders and rare diseases, announces today the top-line results of a Phase II clinical trial of AZP-531, its unacylated ghrelin analog, in patients with Prader-Willi Syndrome (PWS).
This randomized, double-blind, placebo-controlled, European multicenter study was aimed at evaluating the safety, tolerability and efficacy of AZP-531 administered daily subcutaneously for 14 days on food-related behavior, versus placebo. The trial was conducted across seven centers in France, Spain and Italy. It enrolled a total of 47 patients with genetically diagnosed PWS and evidence of hyperphagia, with a mean age of 27 years (range 13-46) and mean BMI of 38 kg/m2 (range 21-67).
The results showed a significant improvement in food-related behavior in patients treated with AZP-531 (p<0.05 versus placebo), as assessed by the Hyperphagia Questionnaire (HQ), the most widely used tool for assessing efficacy in clinical trials in PWS. The results showed a particular improvement in the Hyperphagic Severity domain score of the HQ (p<0.05 versus placebo). These findings were supported by a reduction in appetite following breakfast for patients treated with AZP-531, as assessed by a newly developed patient-reported outcome scale (p<0.001 versus baseline; not significant versus baseline for the placebo group).
Glucose control improved with AZP-531 treatment, with a greater effect observed in patients with higher fasting or post-prandial glucose levels at baseline. Body weight did not change significantly in either group, which is not unexpected following short-term treatment in a study population with a highly variable weight (range of 53-161 kg) and BMI at baseline. However, a significant reduction in waist circumference was noted in the AZP-531 group (p<0.05 versus baseline), which was not observed in the placebo group (not significant versus baseline).
AZP-531 was well tolerated with no serious or severe adverse events and no clinically significant changes with respect to safety laboratory tests.
Results will be presented at the IPWSO Conference, July 20-24, 2016, Toronto, Canada.
"Hyperphagia is a devastating feature of Prader-Willi Syndrome as it dramatically impairs the quality of life of the patients and their families and may also lead to morbid obesity and related cardiovascular complications. In this regard, the impact of AZP-531 on food-related behavior in this trial is clinically relevant, highly promising and calls for the implementation of longer-term clinical trials," said Prof Maïthé Tauber, pediatric endocrinologist, Hospital of Toulouse, and coordinator of the Reference Center for Prader-Willi Syndrome in France. Prof Maïthé Tauber was also the coordinating principal investigator of this study.
Prader-Willi Syndrome is a rare genetic metabolic syndrome characterized by hyperphagia, an excessive eating behavior. Unlike common obesity, Prader-Willi Syndrome is associated with elevated blood levels of acylated ghrelin, a hormone that strongly stimulates appetite. The unacylated ghrelin analog AZP-531 is expected to reduce hyperphagia by counteracting the effects of increased acylated ghrelin blood levels in these patients via a physiological mechanism of action. It is also expected to decrease weight over time and improve glucose control, a key additional benefit as 25% of adult Prader-Willi patients have overt type 2 diabetes.
"We are very pleased with these Phase II results and wish to thank all the investigators and their teams, as well as the patients and their families, who actively participated in this trial," said Soraya Allas, medical director at Alizé Pharma. "We look forward to pursuing the development of AZP-531 with the goal of applying a therapeutic approach to this severe medical condition for which no treatment is currently available."
"The great news provided by these results paves the way for further development of AZP-531. Throughout the four clinical trials performed to date, involving 159 healthy volunteers and patients, AZP-531 has been very well tolerated and has consistently shown positive metabolic effects. Based on the Phase II results in Prader-Willi Syndrome, this first-in-class unacylated ghrelin peptide analog is ready to enter the next stage of development in a well-defined indication," said Thierry Abribat, TAB Consulting, president of Alizé Pharma.
About Prader-Willi Syndrome (PWS)
PWS is a rare genetic disease and the most common form of genetic obesity with an estimated prevalence of 1 to 9 per 100,000. It is a complex clinical syndrome, characterized by life-threatening obesity, short stature, hypogonadism, cognitive, behavioral and psychiatric disturbances. Hyperphagia is the most salient and constant feature of the syndrome. It begins early in childhood and is associated with a lack of satiety. Patients typically display abnormal eating behaviors including obsessive food seeking, food storage, foraging and hoarding, that represent a lifelong source of distress for them and their families. Patients live a dependent life requiring continuous care and supervision. In addition, hyperphagia is associated with significant morbidity and mortality. As a consequence of obesity, up to 25% of adult patients with PWS have type 2 diabetes. Obesity-related complications are the leading cause of death in this patient population. PWS is a unique clinical condition specifically associated with increased levels of acylated ghrelin, a potent orexigenic hormone. There is currently no effective pharmacological treatment for hyperphagia and its associated abnormal eating behaviors.
About the UAG (Unacylated Ghrelin) program
The objective of the UAG program is to develop AZP-531, an analog of unacylated ghrelin, the first product of a new therapeutic class for the treatment of metabolic and cardiovascular disorders. Preclinical and clinical data suggest that unacylated ghrelin and its analogs have the therapeutic potential to address unmet medical needs in the treatment of Prader-Willi Syndrome, type 2 diabetes and some ischemia-related conditions. Alizé Pharma owns a portfolio of 46 pending and granted patents protecting UAG analogs and their therapeutic applications.