Eli Lilly has announced positive topline results from two further Phase III trials of its investigational obesity treatment retatrutide, bringing the company closer to regulatory submission for the once-weekly triple hormone receptor agonist.
The TRIUMPH-2 and TRIUMPH-3 studies met their primary endpoints, with results supporting retatrutide's potential use in people with obesity and associated cardiometabolic complications.
Lilly now plans to submit a Biologics License Application (BLA) to the FDA in the first quarter of 2027, adding that it is currently completing the comprehensive Chemistry, Manufacturing and Controls (CMC) data package required for the BLA.
The additional time needed to compile and verify manufacturing and quality-control information means the filing will come later than the company had previously indicated.
Dubbed the “triple G” drug, retatrutide is an investigational single molecule that simultaneously activates receptors for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon.
The approach is intended to build on the mechanisms of existing incretin-based obesity medicines, including Lilly's dual GIP/GLP-1 agonist tirzepatide.
In TRIUMPH-2, which enrolled adults with obesity or overweight and type 2 diabetes, participants receiving the highest 12 mg dose lost an average of 20.8% of their body weight during 80 weeks, compared with 3.2% for placebo.
The highest dose also produced an average A1C reduction of up to 1.6%.
Meanwhile, participants with severe obesity and established cardiovascular disease in TRIUMPH-3 lost up to 22.6% of their body weight at 80 weeks.
The 12 mg dose was also associated with reductions in several cardiovascular risk factors, including triglycerides, non-HDL cholesterol, systolic blood pressure and high-sensitivity C-reactive protein.
However, these are only surrogate outcomes — the trial did not establish a clear reduction in major adverse cardiovascular events.
Lilly also reported 44 five-point Major Adverse Cardiovascular Event (MACE-5) events — a combined clinical endpoint used to measure serious heart and blood vessel complications — among participants receiving retatrutide, compared with 52 in the placebo group, with the company noting that events occurred less frequently than anticipated in both arms.
The safety profile was broadly consistent with earlier retatrutide studies and the wider incretin drug class, with diarrhoea, nausea and constipation among the most common adverse events.
Treatment discontinuation due to adverse events reached 7.7% in the 12 mg TRIUMPH-2 group and 13.5% in the 12 mg TRIUMPH-3 group.
The latest results follow positive Phase III data from TRIUMPH-1 and TRIUMPH-4, which evaluated retatrutide in other obesity populations and complications.
Lilly says the combined data package could support global submissions for potential indications including obesity, knee osteoarthritis pain and obstructive sleep apnoea.
Detailed TRIUMPH-2 and TRIUMPH-3 results are expected to be presented at future medical meetings and published in peer-reviewed journals.
