Novo Nordisk’s cannabinoid CB1 receptor blocker has run into another problem. Months after sharing obesity data that left investors underwhelmed, the Danish drugmaker has reported the failure of a midphase diabetic kidney disease trial of the molecule.
CB1 receptor blockade is an old idea—Sanofi won approval for a drug with the mechanism in 2006—but Novo identified Inversago Pharma as a company capable of realizing the potential of the approach. Novo acquired the Canadian biotech in a deal worth up to $1.1 billion in 2023. Since then, a mix of lackluster efficacy and concerning safety signals for monlunabant in obesity have taken the shine off the deal.
The program took another hit Wednesday when Novo reported a phase 2 flop. Investigators randomized 254 diabetic kidney disease patients to receive one of two doses of monlunabant or placebo. After 16 weeks of once-daily dosing, people on the study drug did no better than their counterparts on placebo on a measure of kidney function. The result caused the trial to miss its primary endpoint.
Reporting of mild to moderate neuropsychiatric side effects was more frequent with monlunabant than placebo. The safety data add to concerns that the molecule suffers from some of the same problems that held back CB1 blockers in the past. European authorities withdrew the approval of Sanofi’s CB1 obesity drug in 2009 after studies found it doubled the risk of psychiatric disorders.
Novo is yet to share safety and efficacy data from the kidney disease trial, with the only other snippet in the disclosure being the detail that the most common adverse events were gastrointestinal and the vast majority of cases were of mild to moderate severity.
Martin Holst Lange, M.D., Ph.D., the company’s executive vice president of development, told analysts on its financial call Wednesday morning that Novo wasn’t discouraged by the fail, pointing out that “we never did the acquisition of monlunabant to develop it purely for diabetic kidney disease—our focus was on the weight loss potential.”
“Second, I just remind you that that that these are small studies, so obviously, we try to see them in the context of the full picture,” he said.
“When we look at the safety and tolerability profile, it was comparable, albeit at a slightly lower rate than in the dedicated obesity study, basically indicating that we can still have an aspiration of exploring this further in phase 2b with lower doses, looking at weight loss potential, but obviously also—and this has been the intent from the get-go—ruling out a potential safety concern.”