Ascending dose-controlled trial of beloranib, a novel obesity treatment for safety, tolerability, and weight loss in obese women


  • Disclosure: Dr. Hughes: employment, board membership and holding stock at Zafgen, which has filed multiple patents related to the compound and its usage. Dr. Vath: employment and holding stock at Zafgen. Dr. Kim: employment at Zafgen, financial compensation for board membership at Alkermes, DiaMedica and GI Dynamics, and consultant for Gilead, Amylin, Vivus, Lumena, Orexigen, DiaMedica, Metabolon, Alkermes and GI Dynamics, payment for lectures or serving on speakers bureaus at Amylin and Sharp Hospital, and holding stock in Amylin, Orexigen, Vivus, and Zafgen. Dr. Proietto: payment (made directly to the institution, Austin Health) for conducting the study, paid consultant on the medical advisory boards at Novo Nordisk, Janssen, Astra Zenica and Eli Lilly. Dr. Whitehead: funding (paid directly to the institution) from Zafgen to for personnel/consumables to perform assays. Dr. Marjason declares no conflict of interest.

Correspondence: Thomas E. Hughes (Email


Objective: Evaluate the safety and tolerability of beloranib, a fumagillin-class methionine aminopetidase-2 (MetAP2) inhibitor, in obese women over 4 weeks.

Design and Methods: Thirty-one obese (mean BMI 38 kg/m2) women were randomized to intravenous 0.1, 0.3, or 0.9 mg/m2 beloranib or placebo twice weekly for 4 weeks (N = 7, 6, 9, and 9).

Results: The most frequent AEs were headache, infusion site injury, nausea, and diarrhea. Nausea and infusion site injury occurred more with beloranib than placebo. The most common reason for discontinuation was loss of venous access. There were no clinically significant abnormal laboratory findings. In subjects completing 4 weeks, median weight loss with 0.9 mg/m2 beloranib was −3.8 kg (95% CI −5.1, −0.9; N = 8) versus −0.6 kg with placebo (−4.5, −0.1; N = 6). Weight change for 0.1 and 0.3 mg/m2 beloranib was similar to placebo. Beloranib (0.9 mg/m2) was associated with a significant 42 and 18% reduction in triglycerides and LDL-cholesterol, as well as improvement in C-reactive protein and reduced sense of hunger. Changes in β-hydroxybutyrate, adiponectin, leptin, and fibroblast growth factor-21 were consistent with the putative mechanism of MetAP2 inhibition. Glucose and blood pressure were unchanged.

Conclusions: Beloranib treatment was well tolerated and associated with rapid weight loss and improvements in lipids, C-reactive protein, and adiponectin.