Zafgen Completes Enrollment Of Phase 2a Trial Of Beloranib In Hypothalamic Injury-Associated Obesity

Zafgen, Inc. ZFGN, a biopharmaceutical company dedicated to significantly improving the health and well-being of patients affected by obesity and complex metabolic disorders, today announced that the Company has completed enrollment of ZAF-221, a Phase 2a clinical trial of beloranib in the treatment of hypothalamic injury-associated obesity (HIAO). The objective of the study is to evaluate the efficacy and safety of beloranib in HIAO patients over four weeks of randomized treatment, followed by an optional four-week open-label extension. The trial includes 14 obese patients with radiographically confirmed hypothalamic damage who have been enrolled at four trial centers, two in the United States and two in Australia. HIAO is most commonly caused by damage incurred during removal of a central nervous system tumor called craniopharyngioma, but can also result from less common types of hypothalamic injury. Craniopharyngioma is a rare form of benign brain tumor that occurs most commonly during childhood and infiltrates near the optic nerve, pituitary gland and hypothalamus. Following surgical resection and radiation treatment, hypothalamic dysfunction results in hyperphagia and significant obesity in approximately 50% of these patients, causing a variety of co-morbid conditions and a deteriorated quality of life. "The completion of enrollment for the ZAF-221 trial represents an important step forward for both Zafgen and beloranib," said Thomas Hughes, Ph.D., Chief Executive Officer of Zafgen. "ZAF-221 will provide us with a first look in patients with HIAO to determine if beloranib has the potential to be a significant new treatment for patients afflicted with this life altering form of obesity. Zafgen expects to complete this study in the fourth quarter of this year." The ZAF-221 trial consists of randomized, double-blind, placebo controlled, twice-weekly subcutaneous injections of 1.8 mg beloranib or placebo in 14 obese patients with radiographically confirmed hypothalamic damage. The primary outcome measure is change in body weight from baseline to the end of the randomized dosing period of four weeks. Secondary outcomes include changes in the patient's lipid profile, hs-CRP (a marker of systemic inflammation), sense of hunger, and quality of life. "Currently, there is no marketed treatment available for hypothalamic injury-associated obesity. Patients often experience uncontrollable hunger, much like patients with Prader-Willi syndrome, which can result in hyperphagia and significant obesity," said Dennis Kim, M.D., Chief Medical Officer of Zafgen. "We have seen the therapeutic benefits of beloranib demonstrated in five clinical trials for multiple obesity-related conditions to date, and look forward to learning more from this study regarding beloranib's prospects as a potential treatment for HIAO patients." For more information about this trial, please visit www.clinicaltrials.gov. About Beloranib Beloranib is a novel, first-in-class injectable small molecule therapy with a unique mechanism of action that reduces hunger while stimulating the use of stored fat as an energy source. Beloranib is a potent inhibitor of MetAP2, an enzyme that modulates the activity of key cellular processes that control metabolism. MetAP2 inhibitors work, at least in part, by directing MetAP2 binding to cellular stress mediators, and, thus, reducing the tone of signals that drive lipid synthesis by the liver and fat storage throughout the body. In this manner, MetAP2 inhibition increases metabolism of fat as an energy source. Zafgen holds exclusive worldwide rights (exclusive of South Korea) for the development and commercialization of beloranib. Zafgen exclusively licensed beloranib from Chong Kun Dang (CKD) Pharmaceutical Corp. of South Korea. About Hypothalamic Injury-Associated Obesity (HIAO) Hypothalamic injury-associated obesity (HIAO) is most commonly caused by damage incurred during removal of a central nervous system tumor called craniopharyngioma but it can also result from less common types of hypothalamic injury such as a strokes, brain trauma, or radiation therapy to the brain. Craniopharyngioma is a rare form of benign brain tumor that occurs most commonly during childhood and infiltrates near the optic nerve, pituitary gland and the hypothalamus. Treatment of these tumors commonly involves surgical removal of the tumor mass, followed by radiation treatment, which results in disruption or removal of neighboring structures including the hypothalamus. Post-treatment hypothalamic dysfunction results in hyperphagia and significant obesity in approximately 50% of these patients, resulting in a variety of co-morbid conditions and a deteriorated quality of life.Craniopharyngioma-associated obesity occurs in males and females equally and in all races, with the same incidence around the world. The incidence estimates have ranged from 0.13 to 0.17 per 100,000 per year, or approximately 400 to 500 new cases per year in the United States and 650 to 850 new cases per year in the European Union.