Shares in Novo Nordisk dropped by as much as 29% after its new anti-obesity hope CagriSema missed the 25% weight-loss mark investors had wanted to see in the closely-watched Phase III REDEFINE 1 study.
CagriSema (a fixed-dose combination of cagrilintide 2.4mg and semaglutide 2.4mg) achieved 22.7% weight loss after 68 weeks compared with 11.8% with cagrilintide 2.4mg, 16.1% with semaglutide 2.4mg and 2.3% with placebo alone. This was in all participants who adhered to treatment, regardless of dose strength, in the study that used a flexible dosing protocol.
40.4% of CagriSema patients achieved weight loss of 25% or more after 68 weeks, compared with 6.0% of patients on cagrilintide 2.4mg, 16.2% with semaglutide 2.4mg and 0.9% with placebo, the Danish firm announced on the morning of 20 December.
The market reaction was swift and brutal, with Novo’s shares dropping to as low as DKK526 ($73.28), down by 29% shortly after the announcement at 10.45 GMT. The company has been riding high on the blockbuster sales of its incretin products, mainly semaglutide in its various forms (Wegovy for weight loss, Ozempic for type 2 diabetes), leaving it at risk of a correction in the event of a disappointing readout.
At the same 86-week time point, Wegovy managed weight loss of 15% in its pivotal obesity trial STEP-1, and Lilly’s Zepbound (tirzepatide), currently the second best-selling obesity product, achieved 23% at the later point of 72 weeks in its SURMOUNT-1 Phase III trial.
As such, 25% was seen as the benchmark for treatment success.
The other concern was safety. In CagriSema’s Phase II trial in diabetes, the frequency of gastrointestinal adverse events was almost doubled with the combination compared with each component alone, at 58% with the combo versus 32% with semaglutide and 33% with cagrilintide.
In its release, Novo gave no other details, only saying that all three products tested appeared to have a safe and well-tolerated profile. “The most common adverse events with CagriSema were gastrointestinal and the vast majority were mild to moderate and diminished over time, consistent with the GLP-1 receptor agonist class,” it noted.
Martin Holst Lange, head of development, said the company was “encouraged” by CagriSema’s weight loss profile, which was achieved even though only 57% of patients reached the highest CagriSema dose. “With the insights obtained from the REDEFINE 1 trial, we plan to further explore the additional weight loss potential of CagriSema.”
Results from its second pivotal study REDEFINE 2, in adults with type 2 diabetes who are either obese or overweight are expected during the first half of 2025.