Lilly met analysts’ sky-high expectations with 28.3% weight loss over 80 weeks for the triple hormone receptor agonist retatrutide in a highly anticipated readout on Thursday.
People taking Eli Lilly’s next-gen weight loss drug retatrutide lost an average of 70 pounds, or 28.3% weight loss over 80 weeks—an amount typically seen with bariatric surgery, the pharma and analysts said. The results have heaped more credence to the triple hormone receptor agonist’s “supremely strong” profile, according to analysts.
There’s “a new sheriff in town,” BMO Capital Markets quipped on Thursday morning after the results were released.
Truist Securities analysts echoed that excitement. “We believe these data set a new benchmark for anti-obesity medications and will support retatrutide approval and use in patients that are not adequately served with existing incretin options,” the group wrote on Thursday. The firm provided a conservative worldwide peak sales estimate of between $12 and $19 billion, given that retatrutide will likely be reserved for more severe cases of obesity. BMO anticipates a 2027 launch.
The late-stage results from the TRIUMPH-1 study of patients with obesity but not diabetes easily met analysts’ sky-high expectations for the triple hormone receptor agonist. Prior to the Thursday readout, BMO Capital Markets had been expecting weight loss in the range of 27% to 28.5%.
The study examined 4-mg, 9-mg and 12-mg doses. In the latter two groups, weight loss was 25.9% (64.4 pounds) and 28.3% (70.3 pounds), respectively, according to a Thursday release. The low dose, which featured just one dose-escalation step, saw weight loss of 19%, or 47.2 pounds. The study met its primary endpoint of percent change in body weight at 80 weeks.
The placebo-adjusted rate in the high-dose arm was 26.1%, according to BMO’s calculations. This is slightly lower than the 26.6% Lilly reported in the previous TRIUMPH-4 trial but still helped validate the therapy, according to the analysts. The slightly worse result could stem from differences in enrollment, as the TRIUMPH-4 study focused on patients with obesity and osteoarthritis.
The 12-mg group also saw 65.3% of participants achieve a body mass index (BMI) under 30, below the threshold of obesity. For participants starting with a BMI above 40, 37.5% of individuals achieved this milestone.
Improving uptake
The earlier TRIUMPH-4 readout was heralded as a success but did reveal a safety signal called dysesthesia, a neurological condition that causes normal sensations to feel unusual or painful.
The same was shown in the TRIUMPH-1 trial. Rates of dysesthesia rose along with the dose, with 12.5% of patients experiencing the sensation in the 12-mg arm. Patients taking the drug also experienced higher rates of urinary tract infections as compared to the placebo group. Lilly said these events were mild to moderate.
BMO was encouraged by slightly improving rate of dysesthesia and gastrointestinal adverse events. The “slightly lower weight loss is countered with improved safety profile,” the analysts wrote.
“While some investors may have expected better weight loss relative to TRIUMPH-4, we view retatrutide’s significantly improved discontinuation rate and rates of dysesthesia as a positive that is likely to improve uptake when eventually commercialized,” BMO said.
Discontinuation rates were greater with the higher dose group, with 11.3% stopping treatment in the 12-mg arm compared with 4.9% on placebo. In the lowest dose group, just 4.1% of participants discontinued treatment.
Some patients in TRIUMPH-1 with a BMI above 35 on the 12-mg dose continued into an extension phase, losing 85 pounds (30.3% of body weight) at 104 weeks. Lilly also noted improvements in cardiovascular risk factors such as waist circumference, cholesterol and blood pressure.
Better than surgery
Kenneth Custer, president of Lilly Cardiometabolic Health, said the results across dose groups show that retatrutide can be tailored to each patient. The therapy “delivered a level of weight loss long associated with bariatric surgery,” which has long been a standard—although highly invasive—treatment for severe obesity.
BMO concurred with this assessment, suggesting that the low dose provides an option for patients that want “a lower strength presentation of the therapy.”
Truist also backed the bariatric surgery statement, noting that the drug “can consistently deliver weight loss that approximates bariatric surgery levels.”
Lilly did not provide an estimate for FDA filing with the readout, but BMO suspects the data will help support a new drug application later this year.
The pharma plans to present more data from TRIUMPH-1 at the American Diabetes Association Scientific Sessions in June, and will have readouts from other studies in the TRIUMPH program later in the year.
Lilly’s shares were slightly elevated at about $1,024 apiece in pre-market trading on Thursday morning.
