A randomized, placebo‐controlled trial of beloranib for the treatment of hypothalamic injury‐associated obesity. Issue 8 (18th April 2017)

• Record Type: Journal Article
• Authors: Shoemaker, Ashley; Proietto, Joseph; Abuzzahab, M. Jennifer; Markovic, Tania; Malloy, Jaret; Kim, Dennis D.
• Is Part Of: Diabetes, obesity & metabolism. Volume 19:Issue 8(2017)
• Page Start: 1165
• Page End: 1170
• Publication Date: 2017-04-18
• Subjects: antiobesity drug -- appetite control -- clinical trial -- obesity therapy -- phase I to II study -- randomised trial; Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.12928
• Languages: English
• ISSNs: 1462-8902

Abstract

Abstract : Aims: Hypothalamic injury‐associated obesity (HIAO) results from damage to the hypothalamus that often occurs with surgical removal/radiation therapy of tumours in the hypothalamic region, such as craniopharyngioma. There is currently no rigorously studied pharmaceutical treatment for the intractable weight gain and cardiometabolic consequences that occur in patients with HIAO. We aimed to assess efficacy, safety and tolerability of beloranib treatment for 4 to 8 weeks in patients with HIAO. Materials and methods: This Phase 2a, double‐blind, placebo‐controlled study included 14 patients with HIAO, randomized to receive beloranib 1.8 mg or placebo subcutaneously twice weekly for 4 weeks with an optional 4‐week open‐label extension in which all patients received beloranib. The primary endpoint was change in weight from baseline to Week 4. Results: Participants were 64% female, with a mean (SD) age of 32 (9) years, BMI of 43 (7) kg/m 2 and weight of 126 (22) kg. Compared with placebo (N = 4), beloranib 1.8 mg (N = 8) resulted in a mean (95% CI) difference in weight of −3.2 (−5.4, −0.9) kg after 4 weeks. Weight loss continued through the 8 weeks in patients randomized to beloranib (mean −6.2 [−8.2, −4.1] kg). Beloranib treatment was associated with improvements in high‐sensitivity CRP. Adverse events were mild to moderate. No patients who received beloranib discontinued treatment. Conclusion: Beloranib treatment resulted in progressive weight loss in patients with HIAO that was comparable to that observed with beloranib in patients with exogenous obesity. These findings indicate a novel mechanism for treating obesity in patients with HIAO.