As Eli Lilly looks to hold its lead in the lucrative obesity market, the company’s next-gen prospect, the triple-G drug retatrutide, has met the primary endpoint for weight loss in another pivotal study. Though the results show competitive efficacy and tolerability, they may leave some observers slightly underwhelmed based on high expectations.
In the phase 3 TRIUMPH-1 study, Lilly linked its GIP, GLP-1, and glucagon triple hormone receptor agonist to weight loss of up to 28.3% after 80 weeks based on the efficacy estimand, which assessed data based on patients who stayed on the trial regimen without starting other “prohibited” weight loss treatments. Patients on placebo lost an average of 2.2% of their weight using this measure.
While the readout “nominally clears” Wall Street’s placebo-adjusted expectation of 25%, according to analysts with Citi, the result fell short of some expectations and the topline readout lacked data on the effect of the drug on sleep apnea and osteoarthritis pain.
Ahead of the data drop, BMO Capital Markets analysts set 27% to 28.5% placebo-adjusted weight loss as the expected range for the readout. A Thursday note from the BMO team lacks details of whether the ranges refer to the efficacy estimand or the treatment-regimen estimand, which looks at actual outcomes regardless of adherence or other treatments being taken. Either way, the result fell short of the BMO team’s expected range.
In early trading Thursday, Lilly shares moved up about 1.5% from Wednesday’s close.
Digging deeper into the results, on the efficacy estimand, patients on 4 mg retatrutide lost 19% of their body weight after 80 weeks. Those on the 9 mg regimen lost 25.9% and participants in the 12 mg cohort lost 28.3%.
On the treatment-regimen estimand, the weight loss numbers were 17.6%, 23.7% and 25% for the three retatrutide doses compared with 3.9% for placebo
Lilly said all three doses of retatrutide met the primary and key secondary endpoints for obesity, adding that weight loss continued to deepen after Week 80 and hit 29.9% for the treatment-regimen estimand in a subset of patients who continued to take the top dose until Week 104. Citi analysts named the Week 104 readout as the figure that impressed them the most.
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The treatment-regimen estimand data compare favorably to results for other obesity drugs. Tirzepatide, which Lilly sells as Zepbound in obesity, set the previous bar with weight loss of up to 20.9%. Novo Nordisk reported an 18.7% result for the high dose of Wegovy, its rival GLP-1 drug.
The topline data release lacks any information about the effect of the drug on osteoarthritis pain and sleep apnea, which Lilly tracked on the Western Ontario and McMaster Universities Osteoarthritis Index (Womac) and Apnea-Hypopnea Index (AHI). Womac and AHI at Week 80 are two of the four primary endpoints of the study.
Full details from the study will be presented at the American Diabetes Association’s upcoming scientific sessions in New Orleans in June.
In terms of safety and tolerability, 11.3% of patients on the high dose discontinued treatment because of adverse events, compared to 4.9% of people on placebo. The low dose, which achieved 17.6% treatment-regimen estimand weight loss at week 80, had a lower discontinuation rate than placebo, at 4.1%. But gastrointestinal adverse events were about twice as common on the low dose as on placebo.
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Dysesthesia, a neurological condition, affected 20.9% of patients on the high dose. Comparing the data to results from an earlier osteoarthritis trial, BMO analysts said they view “retatrutide’s significantly improved discontinuation rate and rates of dysesthesia as a positive that is likely to improve uptake when eventually commercialized.” The team says Lilly appears in line to submit the drug for potential FDA approval this year.
Retatrutide is a more niche market opportunity for Lilly, Citi analysts said. That assessment reflects the monumental sales of Lilly’s existing obesity drugs, with retatrutide’s $6.6 billion peak consensus sales estimate considered large by most measures.
The readout continues a trend of trial wins for the next-gen prospect. In March, Lilly said the drug helped diabetes patients lower their blood sugar and prompted 16.8% weight loss in a phase 3 study. And at the end of last year, the company touted weight loss of up to 28.7% in a study of patients with obesity and knee osteoarthritis.
