By Patrick Wingrove
Sept 30 (Reuters) – Eli Lilly said on Wednesday its experimental combination weight-loss drug outperformed its blockbuster Zepbound in a head-to-head trial, intensifying the competition with Danish rival Novo Nordisk for new, more effective obesity therapies.
The Indianapolis-based drugmaker said patients with diabetes on the highest tested dose of EloraTZP, which combines tirzepatide and experimental drug eloralintide, lost an average of 23.3% of body weight over 48 weeks. That compared with 14.8% for patients on the highest dose of Zepbound in the mid-stage trial.
Tirzepatide is the active ingredient in Zepbound as well as Lilly’s diabetes drug Mounjaro.
Kenneth Custer, president of Lilly’s cardiometabolic health division, said in an interview that he expected the combo drug would offer “the best balance of efficacy, safety, and tolerability” within Lilly’s obesity portfolio and among competitors.
“The findings provide strong combination proof-of-concept and broaden Lilly’s cardiometabolic portfolio beyond today’s incretin standards,” Citi analyst Geoff Meacham said. Achieving tirzepatide-like weight loss in patients with type 2 diabetes was significant, as diabetes typically tempers treatment efficacy, he added.
Custer said it was possible the combination could lead to even greater weight loss in later trials than retatrutide, another promising Lilly experimental obesity medication. In a late-stage trial, the highest dose of retatrutide drove an average weight reduction of up to 28.3% over 80 weeks in patients without diabetes.
EloraTZP also cut blood sugar levels, lowering A1C by up to 2.9% versus 2.4% for tirzepatide alone, according to data presented at the European Association for the Study of Diabetes meeting in Milan.
Lilly shares fell marginally despite strong efficacy data, as investors focused on adherence and long-term persistence.
“The outsized weight loss benefit is being questioned relative to the discontinuation rates and the reality that this is a dual-drug regime,” said Kevin Gade, COO at Bahl & Gaynor, which holds Lilly shares.
Patients stopped taking EloraTZP in the trial at a rate of 10.8% to 27%, depending on the severity of side effects as multiple doses were tested. That compared with a dropout rate of 0% to 10.8% with eloralintide alone, 2.9% for tirzepatide and 16.7% for those who received a placebo.
The most common side effects were mild to moderate gastrointestinal issues that occurred mainly during dose escalation and were more frequent in the combination arms than with either drug alone, the company said.
“If Lilly can get a handle on the discontinuations and GI tolerability issues, then I think this is looking stronger than retatrutide as a high-efficacy option for patients,” said Morningstar analyst Karen Andersen.
Lilly, in a press conference to discuss the results, said the higher discontinuation rate was due to patients ramping up doses of two drugs at once. It said the company would improve escalation schedules in longer, late-stage trials.
COMPETITIVE LANDSCAPE
The results raise the stakes in a fight between Lilly and Novo for share of the global weight-loss market forecast by some analysts to reach $100 billion to $150 billion annually by the end of the decade.
Novo is on track to launch the first combination obesity drug, CagriSema, early next year. Expectations for that medication took a hit in February when it fell short of Lilly’s high-dose tirzepatide in a head-to-head trial, despite achieving a 23% average weight reduction over 84 weeks.
Novo’s long-term growth prospects continue to rest on pipeline programs beyond CagriSema, led by its next-generation dual-acting tablet zenagamtide, Morningstar’s Andersen said.
The company’s fortunes have reversed sharply from its days of dominating the market with the 2021 arrival of its powerful obesity drug Wegovy that propelled its valuation above $600 billion. The Danish drugmaker’s shares have tumbled more than 70% from their record highs in the face of stiff competition from US rival Lilly.
Eli Lilly executives said it was too early to determine the ideal patient profile for its combination therapy. But they noted that it could serve individuals needing 20% to 30% weight loss, or those who fail to achieve their goals on Zepbound, by targeting a hormone pathway linked to hunger and thoughts about food.
Eloralintide belongs to a class of drugs known as selective amylin receptor agonists, which target a different hormone than GLP-1 drug Zepbound.
In the multi-arm EloraTZP trial of 367 obese or overweight adults with type 2 diabetes in the US and Argentina, eloralintide alone led to an average weight loss of 12.3% on the second highest dose tested, and 11.1% on the highest, while those taking a placebo lost just 3%.
The company said it plans to start late-stage trials for EloraTZP in the fourth quarter of 2026, while late-stage trials of eloralintide in obese and overweight patients with and without diabetes were ongoing.
(Reporting by Patrick Wingrove in London and Mariam Sunny in Bengaluru; Editing by Caroline Humer, Bill Berkrot and Joyjeet Das)
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