CAMBRIDGE, Mass — Zafgen on Wednesday announced initial results from its Phase 2a study of beloranib, a selective inhibitor of methionine aminopeptidase 2 (MetAP2), in patients with Prader-Willi syndrome, a severe form of genetic obesity. These results showed improvements in body weight, hunger-related behaviors and body composition, including reductions in body fat content and preserved lean body mass following four weeks of treatment.
These changes were observed despite the increased caloric intake that was a component of this trial. Known markers of beloranib response, including those associated with cardiovascular disease risk, were also improved, demonstrating that PWS patients responded to the molecular mechanism of beloranib.
“The results of this short-term, proof-of-concept study are very promising and underscore our belief that beloranib has the potential to successfully treat this severe form of obesity. To our knowledge, this study represents the largest placebo-controlled, randomized, multiple-dose trial to date for obesity in this patient population, and these results bode well for further study of beloranib in patients with this devastating condition,” said Thomas Hughes, president and CEO Zafgen.
Similar to results seen in non-PWS obese patient populations, beloranib treatment in this study reduced body fat content by 8.1% vs. placebo in four weeks of treatment at the highest study dose of 1.8 mg, despite a 50% increased daily caloric allowance. Hunger-related behaviors improved, and a trend toward overall improvement in body weight was seen, although this did not reach statistical significance, in part due to the fact that study was not powered to demonstrate these differences.
Key hormones, including adiponectin and leptin, also showed changes characteristic of non-PWS obese patients, demonstrating that the drug was highly active in these patients and had a similar effect to that seen in non-PWS patients.
“These results are very exciting for the treatment of PWS, as most patients showed improvements in body weight, hunger-related behaviors and body fat content, despite the increased food intake included in the trial design,” said Jennifer Miller, associate professor of pediatric endocrinology, University of Florida, and principal investigator for the study. “PWS is a complex genetic disease that is difficult to treat and the results of this trial demonstrate that beloranib has a beneficial impact on this underserved patient population. Notably, we were encouraged by reports of fullness, a first-time occurrence for PWS patients who otherwise lack the capacity to feel sated after meals.”
“PWS patients remain severely impacted by their disease and are not treatable with other anti-obesity agents,” said Janalee Heinemann, director of research and medical affairs for the Prader-Willi Syndrome Association. “PWS represents one of the most severe forms of genetic obesity and we welcome these results, which are a significant step towards finding a treatment for those suffering from this life threatening condition.”
Beloranib, a novel obesity therapy that utilizes a unique mechanism of action, is being studied for its ability to reduce body weight and improve cardiometabolic risk factors in obese patients with and without PWS.