Eli Lilly has declared victory in the first late-stage trial testing tirzepatide’s effect on cardiovascular outcomes, as it looks to catch up with Novo Nordisk and solidify its lead over newer entrants to the GLP-1 race.
In a Phase 3 study, the drug reduced the risk of heart failure outcomes like a heart failure urgent visit or hospitalization, oral diuretic intensification or cardiovascular death by 38% compared to placebo, according to topline data released Thursday.
The late-stage win is the latest reflection of the blockbuster GLP-1 drug class’ promise beyond the initial indications of diabetes and weight loss, where they have racked up billions in sales and generated enormous demand. Lilly is investigating its GLP-1/GIP in metabolic dysfunction-associated steatohepatitis, or MASH, as well as in sleep apnea, while Novo’s Wegovy has also shown promise in reducing the risk of kidney disease progression.
Lilly’s GLP-1/GIP dual agonist — marketed in the US as Mounjaro for diabetes and Zepbound for weight loss — is several steps behind Novo Nordisk and its GLP-1 Wegovy, which was approved by the FDA in March and in the EU in July to reduce the risk of cardiovascular death, heart attack and stroke in adults with heart disease who are also either obese or overweight.
More data will be presented at an upcoming medical meeting, and Lilly said that it plans to submit the data to the FDA and other regulatory agencies later this year.
In Lilly’s 731-patient SUMMIT Phase 3 study, the company investigated three doses of its drug — 5 mg, 10 mg or 15 mg — in adults with heart failure with preserved ejection fraction (HFpEF) and obesity, with or without diabetes.
Tirzepatide showed “statistically significant improvements” in both primary endpoints with a reduction in the risk of heart failure outcomes, which was analyzed as a composite endpoint, as well as improvements in heart failure symptoms and physical limitations, as measured by the Kansas City Cardiomyopathy Questionnaire.
The trial also hit all of the key secondary endpoints, which included improvement in exercise capacity, reductions in the inflammation marker known as high-sensitivity C-reactive protein, and weight reduction. Patients in the trial saw a 15.7% body weight reduction on average compared to 2.2% for placebo.
The safety profile in this study was “consistent” with other studies of Zepbound, with most of the adverse events being gastrointestinal and mild to moderate.
“Previous incretin studies in this population focused on symptoms and physical limitations,” Lilly SVP of product development Jeff Emmick wrote in a statement, adding that the trial is a “first-of-its-kind trial.”
This is in comparison to Novo’s vast (more than 17,000 patients) SELECT trial, which had a different endpoint: reduction of major adverse cardiovascular events (MACE). In that trial, the drug reduced MACEs by 20% in obese or overweight patients without diabetes, and investigated just the 2.4 mg dose of its drug.