Novo Nordisk’s $1 billion bet last year on a small Canadian biotech could expand the Danish drug giant’s arsenal of obesity medicines, but it will first have to address safety concerns.
On Friday, Novo said its experimental drug monlunabant helped people lose weight at statistically significant levels in a Phase 2a trial. The oral small molecule is a CB1 inverse agonist, and Novo acquired it through a takeover of the biotech Inversago Pharma, announced in August 2023.
In the Phase 2a trial, Novo said all once-daily doses of monlunabant hit statistical significance at reducing weight from baseline compared to placebo. But the higher doses didn’t have as much of an impact as expected.
After 16 weeks on the lowest dose of 10 mg, trial participants on its drug experienced a weight loss of 7.1 kg versus 0.7 kg for those taking the placebo. At the higher doses of 20 mg and 50 mg, Novo said there was “limited additional weight loss.”
The data didn’t excite the market. Novo’s US shares $NVO were down about 4.3% Friday morning, while shares of Corbus Pharmaceuticals $CRBP tanked 63% as investors took Novo’s readout as a barometer for Corbus’ pipeline asset — the company has said it planned to start a Phase 1 study next year. Corbus’ shares had risen 755% year-to-date, making it one of the best-performing biotech stocks until this point in 2024.
“Overall, this update disappoints on both efficacy and safety,” TD Cowen analyst Michael Nedelcovych wrote in a note. “Novo sees a path forward, but potential of this early-stage asset is diminished.”
Novo said it will move into a Phase 2b study next year that will include more patients and will test the drug for a longer duration. The drug, also known as INV-202, is also being studied in diabetic kidney disease. That trial completed last month, according to the federal trials database.
A first generation of CB1 drugs was marred by safety in the 2000s, and a marketed drug was pulled in Europe because of suicidality concerns. The drug never made it onto the US market.
But Novo and other drugmakers, including Corbus and Skye Bioscience, are trying to tackle the class with medicines that don’t penetrate the brain nearly as much, hoping to stave off those safety scares.
“We’re taking a new approach, a more profound approach on the biology, and we’re staying out of the brain so that we don’t cause the depressive mood disorders that came with the other ones,” former Inversago CEO François Ravenelle told Endpoints last year.
Martin Holst LangeThe Novo drug isn’t in the clear on the safety front, though. Anxiety, irritability and sleep disturbances were “more frequent and dose dependent with monlunabant compared to placebo,” Novo said. Those side effects were also mild to moderate, it said.
Gastrointestinal side effects were the most common adverse events in the Phase 2a study. The “vast majority” were mild to moderate, the drugmaker said.
“The phase 2a results indicate the weight-lowering potential of monlunabant and that further work is needed to determine the optimal dosing to balance safety and efficacy,” Novo’s head of development Martin Holst Lange said in a press release.