Lilly plans Q1 2027 filing for obesity triple retatrutide

Armed with new pivotal trial results, Eli Lilly plans to file for approval of its keenly anticipated new weight-loss therapy, retatrutide, in the US in the first quarter of next year.

The drugmaker has released top-line data from the TRIUMPH-2 and TRIUMPH-3 studies, which together with its earlier TRIUMPH-1 and TRIUMPH-4 trials, will form the basis of a broad marketing application to the FDA for obesity.

In TRIUMPH-2, adults with obesity or overweight and type 2 diabetes – a group that often face serious difficulties losing weight – lost up to 20.8% of their baseline body weight at 80 weeks with retatrutide, compared to a 4% decline with placebo.

The pattern was similar in TRIUMPH-3, conducted in adults with severe obesity and established cardiovascular disease – with or without type 2 diabetes – with the triple-acting GLP-1, GIP and glucagon agonist achieving up to 22.6% reduction at 80 weeks, versus 3.2% for those in the control group.

The most common side effects in both trials were nausea and diarrhoea, in common with other drugs that work via GLP-1 and other incretin pathways. In TRIUMPH-2, discontinuation rates due to adverse effects were up to 12% with retatrutide, versus 4.9% for placebo, while in TRIUMPH-3 they came in at up to 13.5% and 4.8%, respectively.

"With the positive results from TRIUMPH-2 and TRIUMPH-3, we now have the clinical data package to support global submissions for retatrutide as a potential treatment for obesity, knee osteoarthritis pain, and obstructive sleep apnoea," said Lilly's head of cardiometabolic health, Kenneth Custer.

"We look forward to working with regulators as they evaluate this first-of-its-kind medicine," he added.

Lilly is currently completing the comprehensive chemistry, manufacturing, and controls (CMC) data package required for a Biologics License Application (BLA).

The company sees retatrutide as a successor to its fast-growing dual GIP/GLP-1 agonist Zepbound/Mounjaro (tirzepatide) – now the top-selling weight-loss drug worldwide – and also as a companion to new oral GLP-1 agonist Foundayo (orforglipron) as it battles for market share with main rival Novo Nordisk.

Analysts at Clarivate have concurred, suggesting $30 billion-plus revenues are possible with the triple agonist, and predicting it will become the primary growth driver in the obesity drug market after 2028. Meanwhile, Lilly has also reported impressive data in type 2 diabetes patients in the TRANSCEND-T2D-1 trial.