ESPE Abstracts (2015) 84 P-1-54

'BestPWS EU': A Phase 3 Study in Adolescent and Adult Patients With PWS in Europe

Maithe Tauberc, Terri Kima, Nerissa Krehera, Dennis Kima & Berthold Hauffab


aZafgen, Boston, MA, USA; bUniversitatsklinikum Essen, Essen, Germany; cChildrens Hospital of Toulouse, Toulouse, France


Background: Prader–Willi Syndrome (PWS) is a complex genetic disease; one hallmark of the disease is failure to regulate hunger and metabolism. Hyperphagia and severe obesity contribute significantly to the morbidity and mortality of this disease. Methionine aminopeptidase 2 (MetAP2) inhibition reduces fat biosynthesis and stimulates fat oxidation and lipolysis. Beloranib is a selective and potent MetAP2 inhibitor. In a 4-week phase 2, placebo-controlled, proof-of-concept study in obese, adult PWS patients, beloranib resulted in dose-dependent decrease in body mass and reduction in total fat mass (DXA) despite 50% increase in total daily calorie intake. There was meaningful reduction in food related problem behaviors typical of PWS. Beloranib appeared safe and well-tolerated in this patient population.

Objective and hypotheses: To provide the study design of a phase 3 study being conducted in Europe in adolescent and adult PWS. Primary Objectives include assessment of changes in hyperphagia-related behaviors and total body weight, and safety and tolerability of beloranib over 52 weeks.

Study design: Randomised, double-blind, placebo controlled; 150 obese subjects with PWS 12–50 years old; placebo vs 2.4 mg beloranib (2:3 ratio); a 26 week open-label extension will be offered to patients at the end of the 52 week blinded study period with all patients receiving beloranib.

Results: Dual primary efficacy endpoints include: change in hyperphagia related behavior based upon the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) total score; percent change from baseline in total body weight; key secondary endpoints will be reported including total body fat mass (DXA), LDL and HDL cholesterol; Safety and tolerability will be assessed.

Conclusion: Beloranib shows promise for further development in the treatment of obesity and hyperphagia related behaviors in PWS. A phase 3 study is underway in Europe in adolescent and adult PWS patients.

Conflict of interest: Three authors are employees of Zafgen.

Funding: This work was funded by Zafgen.

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