Lilly advances amylin obesity drug eloralintide to phase 3 trials

Eli Lilly announced today that it will begin late-stage clinical trials of its experimental amylin obesity drug, eloralintide, next month, following positive results from a phase 2 study.

The study enrolled 263 adults who did not have type 2 diabetes and were overweight with at least one obesity-related comorbidity.

In the mid-stage study, each participant was randomly assigned to receive weekly subcutaneous injections of either a placebo or eloralintide at doses of 1, 3, 6 or 9 mg or dose escalations of 6–9 mg or 3–9 mg over the course of 48 weeks.

Patients who received the highest dose of Lilly's investigational drug lost an average of 20.1% of their body weight after 48 weeks. The lowest injection dose of eloralintide helped patients lose 9.5% of their weight, compared to the 0.4% seen in the placebo group.

Study participants who began with 6 mg and increased to 9 mg through a two-step escalation lost 19.9% of their weight at 48 weeks, while those who started at 3 mg and used a three-step escalation lost 16.4%.

The most common side effects were mild to moderate gastrointestinal symptoms and fatigue, which occurred more often in patients taking higher doses of the drug.

However, patients in groups that received gradually increasing doses of the selective amylin receptor agonist experienced fewer side effects, similar to those taking the lowest two doses, the company said in a press release.

These encouraging study results advance Lilly's efforts to solidify its dominance in the booming weight loss space and bring next-generation therapies to market.

The first generation of obesity drugs largely targeted the gut hormone GLP-1, but drugmakers are now developing next-wave therapies aimed at other hormones or designed to preserve muscle mass during fat loss.

Eloralintide is also being studied in a phase 1 trial as a standalone treatment and in combination with Lilly's blockbuster dual GIP/GLP-1 receptor agonist, tirzepatide (Zepbound).

A phase 2 study is also underway to examine the effects of eloralintide alone and in combination with Lilly's long-acting GIP receptor agonist drug candidate, macupatide, in adults with type 2 diabetes who are overweight or obese.

Several other major drugmakers, including AbbVie and Roche, have also invested heavily in experimental amylin treatments.

Earlier this year, AbbVie paid $350 million to secure the rights to Gubra's long-acting amylin analogue (GUB014295), which is currently in phase 1 development.

In collaboration with Roche, Zealand Pharma is testing a rival experimental obesity drug, petrelintide, in a phase 2 study.

Novo Nordisk, Lilly's main competitor in the obesity space, announced earlier this year that it is advancing both injectable and oral versions of its dual GLP-1/amylin receptor agonist, amycretin, into phase 3 trials for patients who are overweight or obese.

Novo and Pfizer are also in the middle of an intense bidding war over Metsera, a New York-based clinical-stage biotech company, with a pipeline that includes a once-monthly injectable amylin drug used to treat obesity and other metabolic diseases. 

Alivia Kaylor is a scientist and the senior site editor of Pharma Life Sciences.