The highest dose of Eli Lilly’s eloralintide led to 20.1% weight loss after 48 weeks in a Phase II trial, exceeding analyst expectations and highlighting a “potentially best in class profile,” according to BMO Capital Markets.
While rival Novo Nordisk battles Pfizer for the right to acquire sparkly obesity startup Metsera, Eli Lilly’s amylin agonist eloralintide achieved weight loss of 20% in a mid-stage study, setting the course for a Phase III trial. William Blair analysts went all in, saying the eloralintide “validates [the] amylin agonist class.”
The Phase II trial featured 263 adults with obesity or who are overweight with at least one obesity-related comorbidity but without type 2 diabetes. The study met its primary endpoint, with patients on the highest dose (9mg), losing a mean 20.1% body weight from baseline after 48 weeks compared to placebo participants who lost just 0.4%. Weight loss decreased with dose size. The results were presented Thursday morning at the annual ObesityWeek meeting in Atlanta.
That is a significant bump from the 11.3% weight loss elicited by eloralintide, in combination with Lilly’s blockbuster GLP-1 tirzepatide, at 12 weeks in June. In a note Thursday prior to the Phase II readout, Leerink analysts called these earlier data “highly compelling.”
The data “highlights a potentially best in class profile, with “clean safety” and “no apparent weight loss plateau in several arms of the study,” BMO Capital Markets analyst Evan Seigerman and colleagues said in a Thursday morning note.
On the safety front, the most common adverse events noted in the trial were mild to moderate gastrointestinal symptoms and fatigue, according to Lilly’s press release. Those adverse events were more frequent in the higher dose cohorts, and were lowered with slower dose escalation, the company noted. Those events were similar to placebo for the lower dose 1 mg and 3 mg arms. In their Thursday note, the Leerink analysts relayed feedback from a key opinion leader (KOL) who pointed to “single-digit percentage nausea and vomiting events in Ph1 data,” but noted that “mood effects warrant close monitoring.”
The KOL also stated that “weight loss greater than 15% would be an encouraging outcome for the study,” according to Leerink.
William Blair additionally noted that eloralintide achieved “Wegovy-like weight loss with significantly improved GI tolerability.”
Based on these Phase II results, Lilly plans to begin enrolling Phase III studies for eloralintide in obesity in December.
Amylin—which Leerink deemed last December in a note to investors to be “the hottest new mechanism for obesity”— acts on several regions of the brain to lower the feeling of being rewarded after eating. Several companies—including Lilly and Novo—have candidates in development targeting the receptor.
Novo’s cagrilintide is being tested alone and in combination with its own GLP-1 blockbuster semaglutide in a duo called CagriSema. The combination drug achieved weight loss of 22.7% after 68 weeks in a Phase III trial last December. However, in what has been broadly deemed an unforced error, the company missed 25% weight loss, a bar set for itself, sending shares tumbling.
CagriSema suffered another miss in March, achieving 15.7% weight loss in patients with overweight or obesity with type 2 diabetes. While these results hit the Phase III REDEFINE 2 trial’s primary endpoint, eliciting a “statistically significant and superior weight loss” versus placebo, analysts were not impressed. In a note to investors at the time, Leerink said expectations for CagriSema at 68 weeks “were higher,” especially given that topline data from the trial released in August 2022 showed 15.6% weight reduction at 32 weeks.
R&D misses like those with CagriSema—and the intensity with which Novo is pursuing Metsera—spurred questions from analysts on the company’s recent third quarter earnings call as to whether management has faith in its current pipeline.
Editor’s Note (Nov. 6): This article has been updated to include analyses from William Blair.
