The readout comes on the heels of CagriSema’s disappointing Phase III performance, where it missed Novo’s projection of 25% weight reduction.
Novo Nordisk unveiled topline Phase Ib/IIa data Friday for its next-generation obesity treatment amycretin, which elicited up to 22% weight-loss in adults with overweight or obesity.
These early findings will help Novo redeem its obesity franchise after last month’s underwhelming late-stage readout of CagriSema, a GLP-1 and amylin analog that industry observers had been viewing as the successor to its semaglutide brands Ozempic and Wegovy. In the Phase III REDEFINE 1 trial, CagriSema cut body weight by 22.7% at 68 weeks—an effect that Novo touted as encouraging at the time, but came below its previous projection of 25% weight-loss.
Novo dipped up to 20% in that trial’s aftermath, losing some $72 billion from its market cap.
Friday’s data come from 125 patients enrolled in a randomized, placebo-controlled and double-blinded Phase Ib/IIa trial. The study combined single-ascending dose, multiple-ascending dose and dose-response designs to assess the efficacy and safety of three different amycretin doses—1.25 mg, 5 mg and 20 mg—over a total treatment duration of up to 36 weeks.
At 20 weeks, patients on the 1.25-mg dose saw a 9.7% drop in body weight, versus 1.9% weight gain in placebo comparators at the same time point. Amycretin was uptitrated to 5 mg by 28 weeks, at which point patients lost 16.2% of their weight, whereas placebo counterparts gained 2.3%.
By 36 weeks, the amycretin dose had been bumped up to 20 mg, resulting in 22% weight-loss. Placebo counterparts at this time point saw a weight increase of 2.0%.
Novo was trading around 12% higher on the Danish stock exchange Friday morning.
Martin Lange, the company’s executive vice president for development, said in a statement that the pharma is “encouraged” by these findings, which “support the weight lowering potential of this novel unimolecular GLP-1 and amylin receptor agonist.”
In an investor note, analysts at BMO Capital Markets wrote that Friday’s amycretin readout will “[reopen] the door in the eyes of investors with a next gen option beyond semaglutide.”
Subcutaneous amycretin “could start to shift the narrative around Novo shares with a next gen therapy in the company’s pipeline that could be competitive with the likes of Lilly’s tirzepatide and retatrutide,” the analysts added.
William Blair analysts, in their own note, pointed out that Novo did not provide safety data in its press release, which “could have better contextualized amycretin’s clinical profile for investors.” Still, the results “further validate the amylin-based approach” in obesity, the analysts wrote.
Amycretin is a long-acting agonist of both the GLP-1 and amylin receptors and works by controlling blood sugar levels and modulating appetite. Friday’s data come from Novo’s subcutaneous formulation of amycretin, but the pharma is also developing an oral version.
At the 2024 annual meeting of the European Association for the Study of Diabetes in September, Novo released Phase I data for oral amycretin, touting what it called a “remarkable” 13% weight-loss at 12 weeks—and pointing to the lack of a plateau effect, suggesting potentially stronger effects with prolonged exposure.
Novo plans to take amycretin into “further clinical development” in obesity and overweight, according to Friday’s news release.
