With weight loss topping 20% at 80 weeks in the Phase 3 TRIUMPH-2 and TRIUMPH-3 trials, Eli Lilly plans to file for retatrutide’s approval in the first quarter of 2027. Previously a filing was expected later this year.
Eli Lilly’s next-generation obesity therapy retatrutide elicited “substantial” weight loss and improved glycemic control in a pair of late-stage studies, paving the pharma’s path for a regulatory application.
“Retatrutide’s two additional positive Phase 3 readouts reinforce its potentially best-in-class efficacy,” BMO Capital Markets told investors in a Thursday morning note, adding that these new data “read positively for retatrutide’s efficacy and overall benefit-risk profile.”
Lilly now expects to file in the first quarter of 2027, pushed back from later this year.
Lilly is running the Phase 3 TRIUMPH-2 trial in patients with obesity or overweight who also have type 2 diabetes. The pharma is also conducting TRIUMPH-3, which focuses on patients with severe obesity and established cardiovascular disease. Both are comparing retatrutide, a weekly subcutaneous injection, versus placebo.
In TRIUMPH-2, a 12-mg dose of retatrutide elicited a 20.8% reduction in body weight at 80 weeks, as compared with a 4% drop in placebo controls, according to a Thursday release. This weight loss effect was attenuated at lower doses of retatrutide, dropping to 19.1% at the 9-mg dose and 12.7% at the 4-mg level. Sugar control, as measured by the blood biomarker HbA1c, likewise improved in retatrutide-treated patients at 80 weeks, Lilly reported.
Meanwhile, in TRIUMPH-3, patients on the 12-mg dose of retatrutide hit 22.6% weight loss at 80 weeks, as compared with a 3.2% decrease in placebo. The 9-mg dose of Lilly’s drug elicited a 21.6% reduction in weight.
The study also showed that major adverse cardiovascular events such as heart attack and death—a key secondary outcome—were less frequent in patients on retatrutide, though the treatment effect was not statistically significant. BMO called the cardiovascular readout “limited,” noting that it “could raise some questions” for Lilly’s long-term TRIUMPH-Outcomes study, which specifically looks at the benefits of retatrutide on heart-related complications.
Nevertheless, “we are encouraged by the directional benefits in those who remained on treatment,” the analysts wrote.
Across both studies, retatrutide “met the primary endpoint,” according to Lilly, though the pharma did not present its statistical analysis.
Highly touted as the company’s next obesity blockbuster, retatrutide activates the GLP-1, GIP and glucagon receptors, triggering insulin secretion from the pancreas and improving the body’s energy expenditure. In May, data from the Phase 3 TRIUMPH-1 study, which enrolled adults who have obesity or are overweight without type 2 diabetes, showed weight loss reaching 28.3% at 80 weeks for the highest dose of retatrutide, versus 2.2% in placebo.
At the time, Kenneth Custer, president of Lilly Cardiometabolic Health, said these figures match “a level of weight loss long associated with bariatric surgery.”
A presentation of the data weeks later at the American Diabetes Association’s annual congress prompted William Blair to write that retatrutide “breaks [a] new record in ‘Weight Loss Olympics.’”
RBC Capital Markets in a Thursday morning note said the weight loss in
TRIUMPH-2 and TRIUMPH-3 was “as expected.” While noting that patients in these trials lost less weight than those in TRIUMPH-1 at the highest doses, RBC said the patients in the recently reported studies “typically lose less weight given their co-morbidities.”
If approved, retatrutide will form the fourth pillar of Lilly’s cardiometabolic franchise, behind the two tirzepatide brands Mounjaro and Zepbound, and the weight loss pill Foundayo. The analytics firm Evaluate last month attributed a valuation of more than $20 billion to retatrutide.
