Novo Nordisk’s CB1 Drug Monlunabant Shows Weight Loss Potential, but Raises Efficacy and Safety Concerns

Weight Loss Results:
Novo Nordisk's monlunabant, a small molecule oral cannabinoid receptor 1 (CB1) inverse agonist, demonstrated significant weight loss in a Phase IIa clinical trial. Participants treated with a once-daily 10 mg dose of monlunabant achieved a weight loss of 7.1 kg compared to a reduction of 0.7 kg with placebo after 16 weeks.

Efficacy and Safety Concerns:
Despite the weight loss, there were reports of mild to moderate neuropsychiatric side effects, such as anxiety, irritability, and sleep disturbances, which were more frequent and dose-dependent with monlunabant compared to placebo. No serious adverse events were reported in relation to neuropsychiatric side effects.

Future Trials:
Novo Nordisk plans to initiate a larger Phase IIb trial in 2025 to further investigate dosing and the safety profile of monlunabant over a longer duration in a global population.

Background:
Monlunabant was part of the $1.1 billion acquisition of Inversago Pharmaceuticals Inc. announced in August 2023. It targets the CB1 receptor, which plays an important role in metabolism and appetite regulation.

Historical Context:
Previous CB1 receptor antagonists, such as rimonabant, were withdrawn from the market due to CNS-mediated neuropsychiatric side effects. The development of second and third-generation CB1R antagonists aims to overcome these issues by selectively targeting peripheral CB1 receptors.