Eli Lilly has linked its amylin agonist eloralintide to up to 20.1% weight loss at Week 48, encouraging the drugmaker to prepare to enter phase 3 next month.
Lilly showed it is a contender for the amylin market in June, when the 11.3% weight loss seen after 12 weeks suggested the drugmaker can overcome ceding a head start to companies including Novo Nordisk. The phase 2 data reinforce the impression that eloralintide can compete against Novo’s cagrilintide and assets AbbVie and Roche picked up in multibillion-dollar deals.
At Week 48, weight loss in patients receiving weekly injections of eloralintide ranged from 9.5% to 20.1% compared to 0.4% with placebo. The trial enrolled 263 adults with obesity or who were overweight with at least one related comorbidity and without Type 2 diabetes.
Lilly saw dose-dependent responses across four cohorts, with patients on 9 mg of eloralintide losing the most weight. The company reported weight loss of 16.4% and 19.9% in two sets of people who received escalating doses of eloralintide that topped out at 9 mg.
Novo has set the bar for amylin drugs with cagrilintide. Combined with the GLP-1 medicine in Ozempic and Wegovy, cagrilintide drove 20.4% or 22.7% weight loss after 68 weeks, depending on which patients were included in the analysis. Weight loss on cagrilintide alone was about 12%. Novo reported 22% weight loss in people who took its dual GLP-1 and amylin receptor agonist amycretin for 36 weeks.
Eloralintide is designed to have increased selectivity on amylin versus calcitonin receptors, differentiating it from other molecules in the class including cagrilintide. The design reflects Lilly’s belief that agonism of amylin, rather than the interactions with calcitonin, drives weight loss.
Lilly said the incidence of gastrointestinal symptoms and fatigue, the most common adverse events, were lower with slower dose escalation. At the two lowest doses, which achieved weight loss of 9.5% and 12.4%, the incidence of the adverse events was similar to placebo. “Malaise” and “affective disorders” were seen in an earlier trial of eloralintide.
The company previously told Guggenheim Securities analysts that there is likely an association between the amylin class and feeling tired. But Lilly saw the tiredness as neither a psychiatric side effect nor a significant overhang for the class, the analysts said. People could just be eating less and have less energy with the amylin mechanism than with other types of weight loss medicine.
Lilly’s release of the eloralintide data lacks details of the planned design of the phase 3 trial. But Kenneth Custer, Ph.D., president of Lilly Cardiometabolic Health, shared details of the company’s positioning of the molecule and potential to combine it with other assets such as GLP-1 receptor agonists.
“These data show that eloralintide, a selective amylin agonist, offers the potential for strong efficacy with improved tolerability and could serve as an alternative to incretin therapies,” Custer said in a statement. “We also are optimistic that it could be a complementary option for patients that need higher levels of efficacy.”