COPENHAGEN, Feb 23 (Reuters) - Novo Nordisk's next-generation obesity drug CagriSema was less effective than Eli Lilly's tirzepatide in a head-to-head trial, the Danish drugmaker said on Monday, in a setback to its efforts to dominate the weight-loss market.

Novo Nordisk is fighting to regain first-mover advantage in the obesity treatment market, where demand for drugs with higher efficacy has surged.

Its US-listed share price fell 7.8% in U.S. premarket trading, while Lilly shares rose more than 3%.

Analysts had forecast prior to the results release that shares would be down at least 10% in the event of this scenario that several had seen as “low risk”.

Novo had positioned CagriSema as a more potent successor to its blockbuster Wegovy and a powerful contender to Lilly's Zepbound, but two previous studies that found it delivered less weight loss than expected had already disappointed investors.

Tirzepatide is on the market and 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.

'WORST-CASE SCENARIO'

"This is a worst-case scenario for Novo, now it is clinically proven that Mounjaro is better than CagriSema," Markus Manns at Novo and Lilly shareholder Union Investment told Reuters. "Novo will have an uphill battle launching CagriSema," he added.

Novo needed CagriSema to support its obesity business after patent cliffs in the early 2030s for Wegovy's active ingredient semaglutide, Manns said.

The trial was designed to show CagriSema was at least as effective as tirzepatide in reducing weight.

Instead it 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 statement said.

"This is a fairly big setback," said Henrik Hallengreen Laustsen, analyst at Jyske Bank.

"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.

NOVO NORDISK PLANS A HIGH-DOSE TRIAL

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, 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.

The Danish drugmaker plans to start a high-dose trial for CagriSema in the second half of this year.

Novo Nordisk's Chief Scientific Officer Martin Holst Lange said the company was "pleased with the weight loss" of 23% for CagriSema in the latest trial in its REDEFINE test programme. He did not explain why he was pleased.