Mixed Results for Novo Nordisk's Oral Weight Loss Drug Trial

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Mixed Results for Novo Nordisk’s Oral Weight Loss Drug Trial

Mixed Results for Novo Nordisk’s Oral Weight Loss Drug Trial

On September 20, Novo Nordisk, the Danish pharmaceutical giant, saw its stock drop nearly 6% in early U.S. trading, reaching a low of $126.13 per share—the lowest since August 9. The decline followed the company’s announcement of the main results from the Phase 2a clinical trial of its weight-loss drug, Monlunabant. While the drug demonstrated statistically significant weight reduction compared to placebo, the additional weight loss benefit at higher doses was limited.

Monlunabant is a small molecule oral CB1 receptor inverse agonist developed by Inversago Pharmaceuticals Inc., which Novo Nordisk acquired last August. The drug is being studied for the treatment of metabolic syndrome, obesity, and diabetic nephropathy.

Mixed Results for Novo Nordisk's Oral Weight Loss Drug Trial

In a previous Phase 1b trial, participants taking Monlunabant* experienced an average weight loss of 3.5 kg (3.3%) over 28 days, along with significant reductions in waist circumference and BMI. The drug was well-tolerated, with no serious adverse events reported.

The recently announced Phase 2a trial involved 243 patients with obesity and metabolic syndrome, who had an average weight of 110.1 kg. They were randomly divided into four groups. Over 16 weeks, three groups received daily doses of 10 mg, 20 mg, and 50 mg of Monlunabant, while the fourth group received a placebo.

The results showed that all Monlunabant dose groups achieved statistically significant weight loss compared to the placebo. Patients in the 10 mg group lost an average of 7.1 kg, while those in the placebo group lost just 0.7 kg. However, higher doses did not lead to significantly greater weight loss beyond the 10 mg group.

No serious adverse events were reported during the trial. The most common side effects were mild gastrointestinal issues. Compared to the placebo, patients on Monlunabant also reported mild to moderate neuropsychiatric side effects, such as anxiety, irritability, and sleep disturbances.

Martin Holst Lange, Executive Vice President of Global Development at Novo Nordisk, stated that the Phase 2a results indicate *Monlunabant’s* potential for weight reduction, but further research is needed to determine the optimal dosage that balances safety and efficacy.

He added that obesity is a complex disease with many unmet needs, and Monlunabant, as an oral small molecule with a novel mechanism of action, is one of Novo Nordisk’s promising projects in the obesity treatment pipeline.

The press release concluded by mentioning that, based on the trial data, Novo Nordisk plans to initiate a larger Phase 2b trial in 2025 to further investigate the long-term safety and efficacy of Monlunabant in a global population.

Interestingly, a similar weight-loss drug called *Rimonabant*, which also targeted the CB1 receptor, was approved in Europe in 2006 but was withdrawn worldwide in 2008 due to severe psychiatric side effects.

In addition to Novo Nordisk, U.S.-based companies Skye Bioscience, Inc., and Corbus Pharmaceuticals Holdings, Inc. are also developing drugs with similar mechanisms. Their stock prices dropped by over 44% and 59%, respectively, following the news about Monlunabant.