Novo Nordisk A/S: Successful Completion of Monlunabant Phase 2a Obesity Trial

Bagsværd, Denmark, 20 September 2024 – Novo Nordisk has announced the headline results from a phase 2a clinical trial evaluating monlunabant, a small molecule oral cannabinoid receptor 1 (CB1) inverse agonist. Monlunabant, previously known as INV-202, was included in Novo Nordisk's portfolio following the acquisition of Inversago Pharmaceuticals Inc. in August 2023.

The clinical trial assessed the efficacy and safety of three different doses of monlunabant—10 mg, 20 mg, and 50 mg—administered once daily, in comparison to a placebo. The study involved 243 participants who had obesity and metabolic syndrome. Participants were randomly assigned to one of the four groups: three treatment groups and one placebo group.

Starting from an average body weight of 110.1 kg, all doses of monlunabant resulted in statistically significant weight loss when compared to the placebo. After 16 weeks of treatment, individuals taking the 10 mg daily dose of monlunabant experienced an average weight reduction of 7.1 kg. In contrast, the placebo group saw a minimal weight reduction of 0.7 kg. Higher doses of monlunabant did not yield significantly greater weight loss.

The most commonly reported adverse events in the trial were gastrointestinal in nature, with most being mild to moderate and dependent on the dosage. Mild to moderate neuropsychiatric side effects such as anxiety, irritability, and sleep disturbances were also reported more frequently and dose dependently in the monlunabant groups compared to the placebo group. There were no serious neuropsychiatric adverse events reported.

Martin Holst Lange, executive vice president and head of Development at Novo Nordisk, commented on the findings, stating, "The phase 2a results highlight the weight-lowering potential of monlunabant. However, additional research is required to determine the optimal dosing to balance safety and efficacy. Obesity is a complex disease with significant unmet needs, and as an oral small molecule with a novel mechanism of action, monlunabant is among the innovative projects in our pipeline aimed at treating obesity."

Following these results, Novo Nordisk plans to initiate a larger phase 2b trial in 2025. This upcoming trial will further explore the appropriate dosing and safety profile of monlunabant over an extended period and in a global population.

Monlunabant functions as an inverse agonist of the CB1 receptor, which is crucial in regulating metabolism and appetite in the central nervous system and in peripheral tissues like adipose tissue, the gastrointestinal tract, kidneys, liver, pancreas, muscles, and lungs. The CB1 receptor plays a vital role in appetite regulation and cardiometabolic pathways.

Novo Nordisk is a prominent global healthcare company established in 1923 and headquartered in Denmark. With a mission to drive change in the fight against serious chronic diseases, the company builds on its long-standing expertise in diabetes. Novo Nordisk is committed to pioneering scientific advancements, increasing access to medications, and working toward the prevention and ultimate cure of diseases. Employing approximately 69,000 people across 80 countries, Novo Nordisk markets its products in about 170 countries. The company's shares are listed on Nasdaq Copenhagen and its ADRs are listed on the New York Stock Exchange.