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In a first-of-its-kind study, tirzepatide also alleviated heart failure symptoms and physical limitations
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Patients on tirzepatide experienced improved exercise capacity, greater weight loss and reduced systemic inflammation
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Lilly has initiated submissions for tirzepatide for the treatment of HFpEF and obesity to global regulatory agencies
INDIANAPOLIS, Nov. 16, 2024 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced detailed results from the SUMMIT Phase 3 trial showing tirzepatide significantly reduced the risk of worsening heart failure events in adults with heart failure with preserved ejection fraction (HFpEF) and obesity. Patients treated with tirzepatide also experienced notable improvements in heart failure symptoms and physical limitations. The results were published in The New England Journal of Medicine simultaneously with a presentation at the American Heart Association (AHA) Scientific Sessions 2024.
Both primary endpoints were met. Tirzepatide showed a 38% reduction in the risk of heart failure outcomes, assessed as a composite endpoint, compared to placebo. Risk of hospitalization for heart failure was reduced by 56%. In addition, patients taking tirzepatide saw a nearly 25-point improvement in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS),1 which measures symptoms and physical limitations associated with heart failure, compared to a 15-point improvement for the placebo group.2
"Many studies point to obesity as a major contributor to the development and severity of heart failure with a preserved ejection fraction through its effects to promote systemic and myocardial inflammation," said Milton Packer, M.D., distinguished scholar in cardiovascular science at Baylor University Medical Center at Dallas and visiting professor at Imperial College, London (steering committee chair). "The SUMMIT trial provides important insights as to how healthcare providers could have a meaningful impact on the clinical course and quality of life of patients with HFpEF and obesity."
All key secondary endpoints were also met, with patients treated with tirzepatide demonstrating improved exercise capacity, walking approximately 30 meters farther in six minutes than those on placebo (38.2 meters vs. 7.9 meters).2 Additionally, patients treated with tirzepatide saw an average reduction in body weight of 15.7%, compared to 2.2% in the placebo group.2 Tirzepatide also significantly decreased high-sensitivity C-reactive protein (hsCRP), a key marker of systemic inflammation, by 43.4%, while the placebo group saw a 3.5% decrease.2
"Cardiometabolic diseases, such as heart failure and obesity, are closely linked and often coexist. New approaches are needed to address the interrelated nature of these diseases. At Lilly, we want to better understand the root causes of these conditions and how they impact each other so we're better able to treat them," said Jeff Emmick, M.D., Ph.D., senior vice president, product development, Lilly. "Currently, no treatments are available specifically for obesity-related HFpEF in the U.S. The SUMMIT data suggest that, if approved, tirzepatide could provide a significant advancement for these patients, potentially setting a new standard of care."
The overall safety profile of tirzepatide in the SUMMIT trial was consistent with previously reported tirzepatide studies. The most frequently reported adverse events were primarily gastrointestinal related and generally mild to moderate in severity. The most common adverse events reported by those on tirzepatide compared with placebo, respectively, were diarrhea (18.4% vs. 6.3%), nausea (17.0% vs. 6.5%) and constipation (14.8% vs. 6.0%). Adverse events led to discontinuation of study treatment in 23 participants taking tirzepatide and five taking placebo.
Additional data from SUMMIT will be presented during AHA and published in peer-reviewed journals. Lilly submitted tirzepatide for the treatment of HFpEF and obesity to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and plans to submit to other regulatory agencies starting later this year.
About SUMMIT
SUMMIT (NCT04847557) was a multi-center, randomized, double-blind, parallel, placebo-controlled Phase 3 study comparing the efficacy and safety of tirzepatide to placebo in adults living with heart failure with preserved ejection fraction (HFpEF) and obesity, with or without type 2 diabetes. The trial randomized 731 participants across the U.S., Argentina, Brazil, China, India, Israel, Mexico, Puerto Rico, Russia and Taiwan in a 1:1 ratio to receive tirzepatide maximum tolerated dose (MTD) 5 mg, 10 mg or 15 mg or placebo. The two primary objectives were: to reduce the risk of time-to-first occurrence of heart failure outcomes and demonstrate improvements in heart failure symptoms and physical limitations from baseline to 52 weeks as measured by the mean change from baseline in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). It is a first-of-its-kind study in patients with obesity-related HFpEF to evaluate both reduction in risk of heart failure events and improvements in function as primary endpoints, in a long-term study with a median follow-up of 104 weeks and exposure up to three years in some patients.
SUMMIT utilized MTD of 5 mg, 10 mg or 15 mg once weekly. The starting dose of 2.5 mg tirzepatide was increased by 2.5 mg every four weeks until MTD was achieved. Participants who tolerated 15 mg continued on 15 mg as their MTD. Participants who tolerated 10 mg but did not tolerate 15 mg continued on 10 mg as their MTD, and participants who tolerated 5 mg but did not tolerate 10 mg continued on 5 mg as their MTD.
About tirzepatide
Tirzepatide is a once-weekly GIP (glucose-dependent insulinotropic polypeptide) receptor and GLP-1 (glucagon-like peptide-1) receptor agonist. Tirzepatide is a single molecule that activates the body's receptors for GIP and GLP-1, which are natural incretin hormones. Both GIP and GLP-1 receptors are found in areas of the human brain important for appetite regulation. Tirzepatide decreases calorie intake and the effects are likely mediated by affecting appetite. Studies of tirzepatide in chronic kidney disease (CKD) and in morbidity/mortality in obesity (MMO) are also ongoing. Lilly submitted data for tirzepatide in moderate-to-severe obstructive sleep apnea (OSA) and obesity to the U.S. Food and Drug Administration (FDA) and other global regulatory agencies earlier this year.
Tirzepatide was approved by the U.S. FDA as Mounjaro® for adults with type 2 diabetes to improve glycemic control on May 13, 2022, and as Zepbound® for adults with obesity or those who are overweight who also have at least one weight-related medical problem on November 8, 2023. Tirzepatide is also commercialized as Mounjaro in some global markets outside the U.S. for adults with obesity or those who are overweight who also have a weight-related comorbid condition.
Tirzepatide is the only approved dual GIP and GLP-1 receptor agonist treatment to reduce excess body weight and maintain weight reduction long term. Both Mounjaro and Zepbound should be used in combination with diet and exercise.
About Lilly
Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable.
References
1.The Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) is a patient-reported outcome instrument that uses a 1-100 point scale to assess heart failure symptoms and physical limitations. Higher KCCQ-CSS values indicate better symptom management and reduced physical limitations in people with heart failure.
2.For the efficacy estimand, which represents efficacy had all participants continued to receive randomized study medication throughout the study.