Eli Lilly is advancing its obesity treatment candidate, which is an alternative to glucagon-like peptide-1 receptor agonists (GLP-1RAs), to Phase III trials.
Eloralintide, an investigational once-weekly, selective amylin receptor agonist, achieved the primary endpoint of superior mean weight reductions in a Phase II trial, with data presented by the company at ObesityWeek 2025 in Atlanta, Georgia, US. The data were simultaneously published in The Lancet.
The study investigated six dosing regimens of the drug, notably 1mg; 3mg; 6mg, 9mg; and two dose escalation cohorts, 6mg-9mg and 3mg-6mg-9mg. These were compared against a placebo in 263 adults with obesity or overweight with at least one obesity-related comorbidity and without type 2 diabetes (T2D).
After 48 weeks, all six treatment arms met the primary endpoint, with weight reductions ranging from 9.5% to 20.1% compared to 0.4% with placebo. The highest reduction was in the 9mg cohort, followed by the 6mg-9mg dose escalation cohort.
All doses of eloralintide also delivered clinically meaningful improvements on secondary endpoints, including body mass index (BMI), as well as improvements across cardiometabolic risk factors including waist circumference, blood pressure, lipid profiles, glycaemic control and markers of inflammation.
The most common adverse events (AEs) were mild to moderate gastrointestinal symptoms and fatigue, which were seen more frequently in the higher dose arms, with the rates lower in the dose escalation cohorts.
Dr Liana Billings, director of clinical and genetics research in diabetes and cardiometabolic disease at Endeavor Health, Skokie, Illinois, said: "Obesity is a complex condition, and no single treatment works for everyone.
"To truly address each patient's needs, we need therapies with different mechanisms of action so that each person can receive the treatment that offers the best balance of effectiveness and tolerability for them.
“These Phase II data suggest eloralintide could offer a promising tolerability profile without compromising on efficacy, underscoring the potential of amylin receptor agonists to expand our therapeutic strategies and better serve individuals living with obesity."
Lilly hopes to initiate the Phase III trials of eloralintide as a monotherapy by the end of 2025 and will also be evaluating its use in combination with incretin therapy.
Obesity market is fast moving
This news drops at a fast-moving time in the obesity market as Lilly’s GLP-1RA therapy, tirzepatide, marketed as Zepbound in obesity and Mounjaro in T2D, has recently overtaken Novo Nordisk’s rival semaglutide, marketed as Wegovy and Ozempic, in sales.
Lilly and Novo have both also come to agreements with the US administration to include their injectable GLP-1RAs on Trump.Rx.gov, with Wegovy and Zepbound set to start at $350 per month and drop to $250 within two years, administration officials said. The deal also cemented Medicare prices of Ozempic, Wegovy, Mounjaro and Zepbound at $245 per month.
Both companies are now hoping to receive decisions on their oral GLP-1RA candidates, which have both shown to be efficacious in Phase III trials. Novo Nordisk could get the greenlight for oral Wegovy before Eli Lilly’s orforglipron as it submitted its application to the US Food and Drug Administration (FDA) earlier. The Trump.Rx.gov deal also included Lilly and Novo Nordisk’s oral candidates, which are set to be available from $149 per month.
As well as this, Novo Nordisk is embroiled in a bidding war with Pfizer to acquire obesity biotech Metsera, as the company attempts to regain a portion of the market share from Eli Lilly. Novo Nordisk has ended up in the throes of a legal case, however, brought forward by Pfizer, which is calling the ‘unsolicited’ attempt to acquire Metsera illegal.
GlobalData forecasts the obesity market will generate $173.5bn in 2031 across the seven major markets (7MM: France, Germany, Italy, Japan, Spain, the UK and the US).
GlobalData is the parent company of Clinical Trials Arena.
