Novo's CB1 Drug Causes Weight Loss in Phase II, Neuropsychiatric Events Noted

Novo Nordisk's acquisition of Inversago Pharmaceuticals for $1.1 billion last year is proving fruitful, as evidenced by the promising Phase IIa results for Monlunabant, an oral therapy obtained through the deal. Monlunabant, a small molecule oral cannabinoid receptor 1 (CB1) inverse agonist, has demonstrated significant weight reduction, shedding 15 lbs over 16 weeks of treatment compared to a mere 1.5 lbs for the placebo group, as detailed in a recent press release.

This new data adds to an already crowded field of recent updates on obesity pills, which include drugs from Roche, Terns Pharmaceuticals, and Novo's amycretin. However, unlike these GLP-1 agonists, Monlunabant uniquely targets the endocannabinoid system.

The study involved 243 patients who were administered three different doses of Monlunabant. Interestingly, the average weight loss of 15 lbs was achieved in the lowest dose group where patients took 10 mg of the drug. Novo noted that higher doses did not result in significantly more weight loss. Unlike many weight loss trials, Novo did not report the weight loss as a percentage of body weight.

On the safety front, Novo reported mostly mild to moderate gastrointestinal side effects. However, there were also reports of mild to moderate neuropsychiatric side effects, including anxiety, irritability, and sleep disturbances. These side effects were more frequent among patients taking Monlunabant compared to the placebo and were dose-dependent. No serious adverse events related to these neuropsychiatric side effects were reported.

Graig Suvannevejh, a senior biopharmaceuticals and biotechnology equity research analyst at Mizuho Americas, mentioned in an interview with BioSpace in August that the CB1 receptor class has had a history of safety concerns, particularly regarding the risk of suicidality. Novo's substantial investment in this space is seen as an indication that the current generation of CB1 receptor therapies may have addressed these safety issues.

Martin Holst Lange, executive vice president and head of development at Novo Nordisk, emphasized that while the results are promising, the company still needs to refine the optimal dosing to balance safety and efficacy. He pointed out that the results highlight the weight loss potential of Monlunabant.

Looking ahead, Novo Nordisk plans to initiate a larger Phase IIb trial to further investigate the dosing and safety profile of Monlunabant. This trial is expected to commence next year.

The Phase IIa results have been eagerly anticipated by analysts who believe that Novo’s success could have significant implications for other companies working on CB1 receptor drugs, such as Corbus Pharmaceuticals and Skye Bioscience.