Novo Nordisk has announced positive headline results from a Phase 2a clinical trial of monlunabant, an oral cannabinoid receptor 1 (CB1) inverse agonist, for the treatment of obesity. The trial, involving 243 participants with obesity and metabolic syndrome, evaluated the efficacy and safety of once-daily doses of 10 mg, 20 mg, and 50 mg of monlunabant compared to placebo over a 16-week period. Monlunabant was acquired as part of Novo Nordisk's acquisition of Inversago Pharmaceuticals Inc. in August 2023.
Weight Loss Efficacy
The Phase 2a trial demonstrated that all doses of monlunabant achieved statistically significant weight loss compared to placebo. Specifically, participants treated with a 10 mg dose of monlunabant experienced a weight loss of 7.1 kg from a baseline of 110.1 kg, compared to a 0.7 kg reduction in the placebo group. The company noted that higher doses of monlunabant did not result in substantial additional weight loss.
Safety Profile
The most common adverse events reported in the trial were gastrointestinal, with the majority being mild to moderate and dose-dependent. Additionally, there were reports of mild to moderate neuropsychiatric side effects, including anxiety, irritability, and sleep disturbances, which were more frequent and dose-dependent with monlunabant compared to placebo. No serious adverse events related to neuropsychiatric side effects were reported.
Future Directions
"The phase 2a results indicate the weight-lowering potential of monlunabant and that further work is needed to determine the optimal dosing to balance safety and efficacy," said Martin Holst Lange, executive vice president and head of Development at Novo Nordisk. He added, "Obesity is a complex disease with a significant unmet need, and as an oral small molecule having a new mechanism of action, monlunabant is one of the novel projects in our pipeline with the potential of treating obesity."
Novo Nordisk plans to initiate a larger Phase 2b trial in 2025 to further investigate the dosing and safety profile of monlunabant over a longer duration in a global population.
About Monlunabant and CB1
Monlunabant functions as an inverse agonist of the CB1 receptor, which plays a crucial role in metabolism and appetite regulation within the central nervous system and peripheral tissues, including adipose tissues, the gastrointestinal tract, kidneys, liver, pancreas, muscles, and lungs. The CB1 receptor is known to influence appetite regulation and cardiometabolic pathways.
