Novo Nordisk’s investigational obesity combination drug, CagriSema (a fixed dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg), underperformed in its latest clinical trial, leading to a dip in the company’s share price.
In response to the trial outcomes, Novo’s shares declined by approximately 8% this week.
Novo shared the latest data from the Phase III REDEFINE 2 trial evaluating the drug in overweight or obese patients with type 2 diabetes.
Although the drug met its primary endpoint of achieving a statistically significant weight reduction compared to placebo, the results fell short of the 25% weight loss target that Novo had been pitching to investors.
In the trial of approximately 1,200 participants with type 2 diabetes and a body mass index (BMI) of 27 or higher, those treated with CagriSema achieved a weight loss of 15.7% after 68 weeks compared to 3.1% with placebo.
The results also fall short compared to Eli Lilly’s rival obesity drug, Zepbound (tirzepatide), which showed weight loss exceeding 22% in similar trials.
Related: Zepbound Versus Wegovy: Head-to-Head Trial Reveals Which Has the Weight Loss Edge
This is the second time CagriSema has failed to reach the 25% target. Results from an initial Phase III trial in December also did not meet expectations, which triggered a 19% decline in Novo’s share price.
Between the two trials, Novo’s case for its semaglutide combination over existing treatments appears to be a tough sell at the moment for both patients and physicians.
CagriSema is a combination therapy that merges semaglutide — the GLP-1 receptor agonist in Novo’s type 2 diabetes and obesity treatments, Ozempic and Wegovy, respectively — with cagrilintide, an amylin analog designed to enhance weight loss and blood glucose control.
When Novo released data from the first trial, it highlighted that 40.4% of patients on CagriSema lost at least 25% of their body weight. However, that figure was not present in the second trial’s readout.
Instead, as one of the trial’s co-primary endpoints, Novo reported that 89.7% of participants achieved at least 5% weight loss after 68 weeks compared to 30.3% in the placebo group.
CagriSema did perform better than Novo’s Wegovy (semaglutide) and Lilly’s diabetes tirzepatide formulation Mounjaro.
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Despite this, Novo shareholder Markus Mann told Reuters that the market “wants Novo to have the best weight loss agent, which is clearly not the case.”
“Novo’s main mistake was to set expectations for CagriSema too high,” he said.
And because of this, investors say previous sales forecasts by industry analysts may have been overly optimistic.
According to Jefferies analysts, an analysis assessing treatment effect irrespective of adherence showed a weight loss of 13.7% — falling short of the 15% or higher required to show superiority over Mounjaro.
The firm had initially estimated peak sales of CagriSema to reach $13 billion, but with the latest trial data, they slashed that projection to $7.25 billion.
William Blair analysts were “especially disappointed” with the trial data, saying that they had expected adults with overweight or obesity and type 2 diabetes to be the patient group where CagriSema had the strongest potential to outperform Lilly’s Zepbound.
They also expressed that “among the dual-acting agents studied (GLP-1/GIP, GLP-1/glucagon, GLP-1/amylin), the combinations pursued by Eli Lilly’s Zepbound, Amgen’s MariTide, Viking’s VK2735 and Roche’s CT-388 appear to offer the most promising approach for achieving broad population weight loss while maintaining a manageable tolerability profile,” in a March 10 note, according to Fierce Pharma.
While Novo’s share price dropped 12% this year to date, Lilly’s stock has increased 13%.
Despite the recent setback, Novo Nordisk plans to seek regulatory approval for CagriSema in the first quarter of 2026, aiming to provide an alternative for patients with obesity and type 2 diabetes.
And the company was more positive about the latest trial data.
“The REDEFINE 2 results confirmed the superior efficacy of CagriSema in people with overweight or obesity and type 2 diabetes,” said Novo Nordisk’s executive vice president for development, Martin Holst Lange. “We look forward to bringing this second pivotal trial to regulatory authorities with the aim of making this next-generation therapy available to the millions of patients in need.”
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