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

• Published in: Obesity (Silver Spring, Md.) Vol. 21; no. 9; pp. 1782 - 1788
• Main Authors: Hughes, T. E., Kim, D. D., Marjason, J., Proietto, J., Whitehead, J. P., Vath, J. E.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.09.2013
• Subjects: 3-Hydroxybutyric Acid - blood; Adiponectin - blood; Aminopeptidases - antagonists & inhibitors; Angiogenesis; Anti-Obesity Agents - adverse effects; Anti-Obesity Agents - pharmacology; Anti-Obesity Agents - therapeutic use; Aspergillus - chemistry; Biological Products - adverse effects; Biological Products - pharmacology; Biological Products - therapeutic use; Blood Glucose - metabolism; Blood Pressure; C-Reactive Protein - metabolism; Cholesterol, LDL - blood; Clinical trials; Cyclohexanes - adverse effects; Cyclohexanes - pharmacology; Cyclohexanes - therapeutic use; Double-Blind Method; Drug dosages; Fatty Acids, Unsaturated - adverse effects; Fatty Acids, Unsaturated - pharmacology; Fatty Acids, Unsaturated - therapeutic use; Female; Fibroblast Growth Factors - blood; Glycoproteins - antagonists & inhibitors; Humans; Hunger - drug effects; Infusions, Intravenous; Laboratories; Leptin - blood; Lipids; Lipids - blood; Methods; Middle Aged; Molecular weight; Obesity; Obesity - blood; Obesity - drug therapy; Risk factors; Sesquiterpenes - adverse effects; Sesquiterpenes - pharmacology; Sesquiterpenes - therapeutic use; Studies; Triglycerides - blood; Weight control; Weight Loss - drug effects; Womens health
• ISSN: 1930-7381; 1930-739X; 1930-739X
• DOI: 10.1002/oby.20356

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.