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

Novo Nordisk's next-generation obesity drug CagriSema underperformed rival Eli Lilly's Zepbound in a head-to-head trial, the Danish drugmaker said on Monday, as it suffered a setback in its fight to regain leadership of the weight-loss market. 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.

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. 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 names Zepbound for weight loss and Mounjaro for diabetes, as well as being marketed as Mounjaro in Europe as a treatment for both.

Novo's shares fell 15% to lows not seen since 2021. The share price slide means that over $400 billion has been knocked off Novo's market capitalisation since a peak in 2024. That erases the gains after Wegovy's launch in 2021 that made Novo temporarily Europe's most valuable listed firm. Lilly's shares rose in pre-market trading.

The company had positioned CagriSema as a more potent successor to its current weight-loss drug Wegovy that faces patent cliffs after 2030. It hoped it would be a powerful contender to Zepbound as it seeks to regain its market leadership. CagriSema contains a new molecule, cagrilintide, as well as semaglutide, the active ingredient in its blockbuster drugs Ozempic and Wegovy.

"This is a worst-case scenario for Novo, now it is clinically proven that Mounjaro is better than CagriSema," a shareholder at Union Investment told Reuters, adding Novo now faced an "uphill battle" with the drug. "The base case was that Mounjaro and CagriSema are similar... Upside was superiority, but nobody had on the agenda, that Cagri would be worse than Mounjaro."

"Weight loss of 23% versus 25.5% after 84 weeks may seem like a minor difference, but to investors it's very significant," said an analyst. "In a winner-takes-all world Eli Lilly has cemented its strong momentum."

An analyst at Jyske Bank called the news a "fairly big setback" for Novo. "When we look at long-term estimates for Novo, CagriSema makes up a fairly large part of Novo Nordisk's growth," he said, adding that, according to consensus, 60% of Novo's growth will come from CagriSema.