Lilly Announces Positive Phase 3 Results of Tirzepatide in Moderate-to-Severe Obstructive Sleep Apnea

• Study met primary endpoint, tirzepatide reduced moderate to severe OSA by 62.8% (approximately 30 events/hour)
  
  

• In the key secondary endpoints of two clinical studies, 43.0% and 51.5% of subjects receiving the highest dose of tirzepatide met the disease remission criteria, as defined by the Apnea Hypopnea Index and the Epworth Sleepiness Scale.
  
  

• Eli Lilly and Company has submitted an application to the U.S. Food and Drug Administration (FDA) for tirzepatide as a treatment for moderate to severe OSA in patients with obesity, and will file applications with other global regulatory authorities in the coming weeks.
  
  

Eli Lilly and Company announced detailed results from the SURMOUNT-OSA Phase 3 clinical trial, which evaluated tirzepatide (10mg or 15mg) in obese participants with moderate to severe obstructive sleep apnea (OSA) who were receiving or not receiving positive airway pressure (PAP) therapy. In both studies, tirzepatide met the efficacy estimation objectives.ⁱ And Treatment Plan Estimation ObjectivesⁱⁱAll primary endpoints and key secondary endpoints. Compared with the placebo, the tirzepatide group showed an average reduction of 62.8% in the apnea-hypopnea index (AHI) (the number of times breathing was restricted or airflow was completely blocked during sleep decreased by approximately 30 times per hour). The full results of the study were published in The New England Journal of Medicine (NEJM) and presented at the 84th Scientific Sessions of the American Diabetes Association.^®Announced at the scientific conference seminar.

Statement:
1. The relevant indications for the drugs described in this article have not been approved in mainland China.
2. Eli Lilly does not recommend the use of any approved and/or unapproved drugs/indications.

For the key secondary endpoint, the efficacy estimand showed that 43.0% (Study 1) and 51.5% (Study 2) of subjects receiving the highest dose of tirzepatide met the criteria for disease remission. Here, "disease remission" means that the subjects achieved an AHI below 5 events per hour or an AHI between 5-14 events per hour with an Epworth Sleepiness Scale (ESS) score ≤10. The Epworth Sleepiness Scale (Epworth Sleepiness Scale, ESS) is a standard questionnaire used to assess the degree of excessive daytime sleepiness.^1-4

OSA is a complex disease that can lead to severe cardiometabolic complications, including hypertension, coronary heart disease, stroke, heart failure, atrial fibrillation, and type 2 diabetes. Compared with placebo, subjects receiving tirzepatide in two studies showed significant improvements in all key secondary endpoints, including systolic blood pressure, hypoxia load, and the inflammatory marker high-sensitivity C-reactive protein (hsCRP).

Peter C. Farrell, Chairman, Professor in the Department of Medicine at the University of California, San Diego, and Dr. Atul Malhotra, Director of the Sleep Medicine Division at the Health Center, stated: "In the trial, obese subjects with moderate to severe OSA who received tirzepatide treatment experienced a reduction of approximately 30 events per hour in sleep disturbances, and nearly half of the subjects showed disease remission. OSA can severely disrupt daily life, and if left untreated, may lead to serious cardiometabolic complications, affecting patients' long-term health. These newly released research data demonstrate the efficacy of tirzepatide in the obese population with moderate to severe OSA, and tirzepatide could potentially bring a new treatment option to the field of OSA therapy."

Detailed Research Results:

Image Source: Eli Lilly Official WeChat

*For SURMOUNT-OSA Study 1 and Study 2, the maximum tolerated dose of tirzepatide administered once weekly is 10 mg or 15 mg. The starting dose of tirzepatide is 2.5 mg, increasing by 2.5 mg every 4 weeks until the maximum tolerated dose is reached. Subjects who tolerate 15 mg may continue treatment with 15 mg as the maximum tolerated dose. Subjects who tolerate 10 mg but not 15 mg will continue treatment with 10 mg as the maximum tolerated dose.

Jeff Emmick, MD, Senior Vice President of Product Development at Eli Lilly and Company, stated: "Currently, there is no drug treatment that can directly address the root cause of OSA. OSA is a complex condition affecting 80 million people in the United States alone and can lead to serious complications. The SURMOUNT-OSA results show that a significant proportion of obese patients with moderate to severe OSA who were treated with tirzepatide achieved disease remission based on pre-specified AHI and ESS criteria, which may imply that PAP therapy could potentially be discontinued in such cases."^4-9

In the SURMOUNT-OSA study, the overall safety profile of tirzepatide was consistent with the results previously reported in the SURMOUNT and SURPASS series of trials, with the most common adverse events being gastrointestinal-related, generally mild to moderate in severity. In SURMOUNT-OSA Study 1, the most common adverse events with tirzepatide compared to placebo were diarrhea (26.3% vs 12.5%), nausea (25.4% vs 10.0%), and vomiting (17.5% vs 4.2%); in SURMOUNT-OSA Study 2, they were diarrhea (21.8% vs 8.8%), nausea (21.8% vs 5.3%), and constipation (15.1% vs 4.4%). Adverse events led to discontinuation of study treatment in 9 tirzepatide-treated participants (5 in Study 1 and 4 in Study 2) and 10 placebo-treated participants (2 in Study 1 and 8 in Study 2).

In regions such as the United States and Europe, tirzepatide is the only approved glucose-dependent insulinotropic polypeptide (GIP)/ glucagon-like peptide-1 (GLP-1) receptor agonist for long-term weight management. Eli Lilly and Company has submitted an application to the U.S. Food and Drug Administration (FDA) for the use of tirzepatide in treating moderate to severe obstructive sleep apnea (OSA) in patients with obesity. Regulatory feedback is expected as early as the end of this year. The FDA has granted Eli Lilly's application Fast Track designation.

About SURMOUNT-OSA

SURMOUNT-OSA (NCT05412004) is a multicenter, randomized, double-blind, parallel, placebo-controlled master protocol study designed to compare the efficacy and safety of tirzepatide versus placebo in obese adult patients with moderate to severe obstructive sleep apnea who are unable or unwilling to use positive airway pressure (PAP) therapy (Study 1), as well as in obese adult patients planning to continue using PAP therapy during the trial period (Study 2). According to the master protocol design, 469 subjects from the United States, Australia, Brazil, China, the Czech Republic, Germany, Japan, Mexico, and Taiwan, China were randomly assigned in a 1:1 ratio to receive the maximum tolerated dose of tirzepatide, either 10mg or 15mg, or placebo. The primary endpoint of these two studies is to demonstrate the superiority of tirzepatide over placebo in terms of the change from baseline in the apnea-hypopnea index (AHI) at 52 weeks.

In the SURMOUNT-OSA trial, the maximum tolerated dose of tirzepatide administered once weekly was 10mg or 15mg. The starting dose of tirzepatide was 2.5mg, increasing by 2.5mg every 4 weeks until the maximum tolerated dose was reached. Subjects who tolerated 15mg continued to receive 15mg as the maximum tolerated dose for treatment. Subjects who tolerated 10mg but not 15mg continued treatment with 10mg as the maximum tolerated dose.

References
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Editor: Mu Mian

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