Lilly reports 20% weight loss with amylin-targeting drug

Eli Lilly has raised the stakes in the obesity market with midstage data for an amylin-targeting drug, eloralintide, that helped overweight people lose up to a fifth of their body weight. The data sets the stage for a phase 3 programme.

While it's not uncommon for strong results in phase 2 falling back a little in large phase 3 trials, the result suggests eloralintide could be a potent new drug for weight loss that could complement Lilly's fast-growing GIP/GLP-1 agonist Zepbound/Mounjaro (tirzepatide).

In the phase 2 trial – which was presented at the ObesityWeek congress and simultaneously published in The Lancet – a weekly injection with eloralintide given at various doses between 1 mg and 9 mg achieved weight reductions of 9.5% to 20.1% at 48 weeks, compared to 0.4% with placebo.

The trial included 263 obese or overweight adults with at least one obesity-related comorbidity and without type 2 diabetes. It showed a clear dose-response relationship with the 20.1% weight reduction seen with a 9 mg dose.

However, a third of patients experienced nausea at that dose, and 43% reported fatigue, although that could be reduced by stepping up dosing over the study period from 3 mg to 9 mg.

Lilly is wasting no time in advancing the programme and said it would start phase 3 testing of the drug next month and is "evaluating its use as a complementary treatment to incretin therapy." Along with Zepbound, Lilly's incretin pipeline includes a daily oral GLP-1 agonist, orforglipron, that is due to be filed for approval in the coming weeks.

In phase 3 trials, Zepbound achieved weight reductions of up to 20.2%, while the fall with orforglipron has been up to around 12%.

Lilly's main competitor in the obesity market, Novo Nordisk, is developing an injectable combination of its GLP-1 agonist semaglutide with amylin agonist cagrilintide, called CagriSema, which disappointed in an initial phase 3 readout with weight loss of 22.7%, below its target of 25%. It is also developing a dual GLP-1/amylin drug called amycretin, in both injectable and oral formulations, with phase 3 trials scheduled to start early next year.

Meanwhile, Metsera – currently the object of a takeover battle between Novo Nordisk and Pfizer – has an amylin agonist ready to start phase 3 testing, Roche is planning phase 3 for Zealand Pharma-partnered petrelintide, and AstraZeneca has another (AZD6234) in phase 2.

Shares in Lilly were up 2% at the time of writing, extending an upwards trend of around 10% since its third-quarter results update a week ago.