Novo Nordisk's CagriSema Underperforms Eli Lilly's Zepbound in Head-to-Head Obesity Trial

Novo Nordisk's next-generation obesity drug CagriSema underperformed Eli Lilly's Zepbound in a head-to-head trial, the Danish drugmaker said on February 23, as it suffered a setback in its fight to regain leadership of the weight loss market. The trial showed CagriSema achieved a 23% reduction in body weight over 84 weeks, compared to 25.5% for Eli Lilly's tirzepatide in the trial.

Novo's shares fell 15% to lows not seen since 2021. Few analysts had predicted CagriSema would be found to be less effective than Lilly's drug that sells as Zepbound in the U.S. and Mounjaro in Europe. Lilly's shares rose in pre-market trading.

The company positions CagriSema as a more potent successor to its current weight loss drug Wegovy that faces patent expiries after 2030. It hoped it would be a powerful contender to Zepbound as it seeks to regain its market leadership, but the data released left some analysts and investors doubting that.

The trial was designed to show CagriSema was at least as effective as tirzepatide in reducing weight. Tirzepatide is sold in the United States under the brand name Zepbound for weight loss and Mounjaro for diabetes, as well as being marketed as Mounjaro in Europe as a treatment for both.

CagriSema is a weekly injection combining cagrilintide, which mimics pancreatic hormone amylin, and semaglutide, the active ingredient in Wegovy that mimics the gut hormone GLP-1. In the study involving around 800 patients mainly in the U.S., Novo tested a fixed-dose combination of cagrilintide 2.4 milligrams and semaglutide 2.4 mg, while patients on tirzepatide received a 15-milligram dose.

Novo executives sought to strike an optimistic tone in calls with investors and journalists. They said CagriSema still has the potential to deliver the highest weight loss of any drug on the market after its expected approval by the U.S. FDA by the end of this year and launch next year. The company plans to start a high-dose trial for CagriSema in the second half of this year.

The chief scientific officer said Novo was "a little bit surprised" at Zepbound's performance in the trial and expected that other trials would establish the drug's potential. He said the "open-label" trial design – both the administrators and the participants knew which drug was being given – likely introduced bias in favour of Zepbound, given the drug is well-known and commercially established.

The share price slide has reduced Novo's market capitalisation by more than $400 billion since a peak in 2024 and erased the gains after Wegovy's launch in 2021 that made Novo temporarily Europe's most valuable listed firm. Monday's share price fall is not the first time that Novo shares have plunged on CagriSema trial data. In December 2024, Novo shares lost $125 billion in a day when results from the first trial of CagriSema were published.

While Novo's study published included data for both the drugs over a period of 84 weeks, previous studies have focused on the effects of treatment over fewer weeks.