Across the 6-month duration of the trial, weight loss was maintained across all dose levels, with patients that had the lowest baseline leptin levels benefitting the most.
Murray Stewart, MD
In new clinical trial data, metreleptin produced greater losses in weight for patients with low leptin levels that were overweight or obese, in comparison with placebo.
Previously, from data pooled post-hoc from an analysis of 4 studies with 1064 patients, in adults with a body mass index (BMI) of 27.0 kg/m2 to 40.0 kg/m2, the therapy reduced weight the subgroups of patients with low baseline leptin levels.
Data from an ensuing study, presented at the American Diabetes Association’s 78th Annual Scientific Session in Orlando, Florida, revealed similar results from patients (n = 267) that were either administered a 10-mg (n = 74) or 20-mg (n = 72) dose of the Novelion Therapeutics leptin analogue or placebo (n = 111).
Murray Stewart, MD, co-author of the study and the executive vice president and head of research and development for Novelion, told MD Mag that while leptin, which is an important hormone in not only regulating hunger, in regulating fat metabolism, correlates well with fat mass, it doesn’t operate properly for some individuals.
“Unfortunately, some people have abnormal signaling of leptin, and these people can eat, and they don’t feel full,” Stewart said. “The leptin isn’t working. Often these people who are obese have very high leptin. We also know people have very low leptin, and therefore they’re hungry and gain weight, but what happens for some reason their leptin levels don’t increase. The goal of our hypothesis was that if we take people with low leptin that are obese, and give them leptin, will it help them lose weight?”
The study included adults with low baseline leptin levels (baseline, 14.2 ng/mL [SD, 13.3]; women, ≤16 ng/mL; men, ≤5 ng/mL) and a BMI of 27.5 kg/m2 to 38.0 kg/m2 and lasted 24 weeks. It showed that both 10- and 20-mg doses of metreleptin decreased weight over time, with the 10-mg dose reporting roughly a 3% loss and the 20-mg dose reporting an estimated 4% loss by week 24.
The 20-mg dose revealed statistically significant weight decreases of more than 2% by week 8 (P <0.1), regardless of whether the patients had high or low baseline leptin levels. Across the 6-month duration of the trial, weight loss was maintained across all dose levels, with patients that had the lowest baseline leptin levels benefitting the most.
“We are very pleased with the data indicating metreleptin’s activity in a population of overweight and obese adults with low baseline leptin levels, who are in need of options to help them lose weight and control the metabolic complications associated with their disease,” Stewart said in a statement. “This is encouraging because it suggests that leptin replacement shows promise in the treatment of overweight and obese adult patients suffering from hypoleptinemic metabolic disorders [HMD] who are characterized by very low leptin levels.”
Most adverse events were mild to moderate in severity, with the most common reported benig injection-site reactions, headache, fatigue, gastrointestinal events, and upper respiratory tract infection.
Murray added that based on the data, Novelin is planning to initiate a Phase 2 proof-of-concept study in HMD before the end of 2018. Metreleptin is currently approved by the US Food and Drug Administration for use as an adjunct to diet to treat complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy.
The study, “Efficacy of Metreleptin for Weight Loss in Overweight and Obese Adults With Low Leptin Levels,” was published in Diabetes.
Related Coverage >>>