Novo Nordisk's CB1 Receptor Blocker Faces Setbacks in Kidney Disease and Obesity Trials

Novo Nordisk's recent acquisition of Inversago Pharma and its cannabinoid CB1 receptor blocker, monlunabant, has encountered significant challenges in clinical trials. The Danish pharmaceutical giant reported disappointing results from a phase 2 trial in diabetic kidney disease, raising concerns about the drug's efficacy and safety profile.

Kidney Disease Trial Failure

Novo Nordisk announced that its phase 2 trial of monlunabant in diabetic kidney disease failed to meet its primary endpoint. The study, which involved 254 patients randomized to receive one of two doses of monlunabant or placebo, showed no significant improvement in kidney function after 16 weeks of once-daily dosing compared to the placebo group.

The trial's failure is a setback for Novo Nordisk's ambitions to expand its pipeline in the kidney disease space. Martin Holst Lange, Executive Vice President of Development at Novo Nordisk, had previously indicated plans to build out the company's kidney disease portfolio in the coming years.

Safety Concerns and Neuropsychiatric Side Effects

Adding to the disappointment of the efficacy results, the trial also raised safety concerns. Patients treated with monlunabant reported a higher frequency of mild to moderate neuropsychiatric side effects compared to those receiving placebo. This finding echoes historical issues with CB1 receptor blockers, notably Sanofi's obesity drug that was withdrawn from the European market in 2009 due to doubled risks of psychiatric disorders.

While Novo Nordisk has not released detailed safety and efficacy data from the kidney disease trial, they did disclose that the most common adverse events were gastrointestinal, with the majority being mild to moderate in severity.

Implications for Obesity Program

The setback in the kidney disease trial compounds existing concerns about monlunabant's potential in obesity treatment. Previous obesity trial data had already left investors underwhelmed, and the emergence of neuropsychiatric side effects mirrors issues that have plagued CB1 receptor blockers in the past.

Despite these challenges, Novo Nordisk continues to list monlunabant in its midstage diabetes and obesity pipeline. A phase 2 weight-loss trial is ongoing and nearing completion. However, Martin Holst Lange acknowledged in a recent investor event that the side effects observed at higher doses would be commercially unacceptable, though he remained cautiously optimistic about the program's future.

As the pharmaceutical industry watches closely, Novo Nordisk faces critical decisions about the future of monlunabant and its $1.1 billion investment in Inversago Pharma. The company's next steps, particularly regarding the planned phase 2b trial in obesity, will be crucial in determining the fate of this once-promising CB1 receptor blocker.