Novo's next-generation CB1 drug leads to weight loss in Phase II, but neuropsychiatric events are reported

Novo Nordisk's $1.1 billion acquisition of Inversago Pharmaceuticals last year is paying off as Phase IIa results from an oral therapy acquired as part of the deal are now in. Monlunabant, an oral small molecule inverse agonist of cannabinoid receptor 1 (CB1), has led to weight loss of 15 pounds after 16 weeks of treatment, compared to just 1.5 pounds with placebo, according to a Press release from Friday.

The data amplifies the flood of Results on obesity pills this month, according to data from Roche And Terns Pharmaas well as Amycretin from NovoHowever, all three of these drugs are GLP-1 agonists, while monlunabant targets the endocannabinoid system.

The study evaluated 243 patients with three doses of monlunabant. In the lowest dose group, where patients received 10 mg, an average weight loss of 7 kg was achieved. Novo said that “limited additional weight loss was seen with higher doses of monlunabant.” Novo did not report weight loss as a percentage of body weight, as is often the case in weight loss studies.

In terms of safety, Novo recorded mostly mild to moderate gastrointestinal side effects, but also said there were reports of “mild to moderate neuropsychiatric side effects” such as anxiety, irritability and sleep disturbances. These events occurred more frequently in patients taking the study drug than in those taking a placebo and were dose-related. No serious side effects were reported due to these neuropsychiatric side effects, Novo said.

Graig Suvannevejh, senior biopharmaceuticals and biotechnology equity analyst at Mizuho Americas, said BioSpace in August that there have been safety concerns about this class in the past, particularly in relation to the Suicide riskNovo's billion-dollar bet on this area was seen as confirmation that the next generation of CB1 receptor therapies had overcome the problems.

Martin Holst Lange, executive vice president and head of development at Novo, said in a statement that the company needs to learn more about optimal dosing to balance safety and efficacy, but the results suggest monlunabant's weight loss potential.

Novo plans to initiate a larger Phase IIb trial to further evaluate the dosing and safety profile of monlunabant, which is expected to begin next year.

The Phase IIa results were eagerly awaited by analysts, who said Novo's success here could have major implications for two smaller biotech companies also working on drugs targeting the CB1 receptor, Corbus Pharmaceuticals and Skye Bioscience.