Company Announcements

• In the primary endpoint, tirzepatide reduced moderate-to-severe OSA severity by up to 62.8% (about 30 fewer events per hour)
• In a key secondary endpoint from two clinical studies, 43.0% and 51.5% of participants taking tirzepatide at the highest dose reached the criteria for disease resolution as defined by apnea-hypopnea index and Epworth Sleepiness Scale measures
• Lilly submitted tirzepatide for the treatment of moderate-to-severe OSA to the U.S. Food and Drug Administration (FDA) and will initiate submissions for other global regulatory agencies in the coming weeks

TORONTO , June 24, 2024 /CNW/ - Lilly Canada announced detailed results from the SURMOUNT-OSA phase 3 clinical trials evaluating tirzepatide injection (10 mg or 15 mg) for the treatment of moderate-to-severe obstructive sleep apnea (OSA) in adults with obesity, with and without positive airway pressure (PAP) therapy. In both studies, tirzepatide achieved all primary and key secondary endpoints for both the efficacyⁱ and treatment-regimenⁱⁱ estimands and demonstrated a mean reduction of up to 62.8% on the apnea-hypopnea index (AHI), or about 30 fewer events restricting or blocking a person's airflow per hour of sleep, compared to placebo. Full results were published in The New England Journal of Medicine (NEJM) and presented at the American Diabetes Association^® (ADA) 84^th Scientific Sessions.

In a key secondary endpoint, the efficacy estimand showed that 43.0% (Study 1) and 51.5% (Study 2) of participants treated with tirzepatide at the highest dose met the criteria for disease resolution. In this context, "disease resolution" means achieving an AHI of fewer than 5 events per hour, or an AHI of 5-14 events per hour and an Epworth Sleepiness Scale (ESS) score of ≤10. ESS is a standard questionnaire designed to assess excessive daytime sleepiness.^1-4 

OSA is a complex disease that can impact the progression of serious cardiometabolic complications, including hypertension, coronary heart disease, stroke, heart failure, atrial fibrillation and type 2 diabetes.⁵ Participants treated with tirzepatide in both studies experienced significant improvements in all key secondary endpoints including systolic blood pressure, hypoxic burden, and high-sensitivity C-reactive protein (hsCRP), an inflammation marker, compared to placebo. 

"Obstructive sleep apnea is a very common, under recognized disease. When untreated, it can lead to many serious adverse health impacts." says Dr. Najib Ayas Professor of Medicine, University of British Columbia. "The SURMOUNT-OSA phase 3 clinical trial data is compelling as the majority of patients treated with tirzepatide experienced 30 fewer disruptive events every hour of sleep and nearly half achieved disease resolution. This is an important study and provides a potential new tool to treat adults living with moderate-to-severe OSA which is greatly needed."

*For both SURMOUNT-OSA study 1 and study 2, Tirzepatide MTD is maximum tolerated dose of 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 maximum tolerated dose was achieved. Participants who tolerated 15 mg continued on 15 mg as their maximum tolerated dose. Participants who tolerated 10 mg but did not tolerate 15 mg continued on 10 mg as their maximum tolerated dose.

"One in five Canadians are impacted by obstructive sleep apnea (OSA) and this complex disease is linked to very serious health complications," says Dr. Sandy Henderson, Vice President, Medical Director, Lilly Canada. "Tirzepatide demonstrated that patients with moderate-to-severe OSA with obesity were able to achieve OSA disease resolution based on predetermined AHI and ESS measures. The SURMOUNT-OSA data is promising and provides a potential new treatment option for some patients with OSA."

The overall safety profile of tirzepatide in SURMOUNT-OSA studies was similar to previously reported SURMOUNT and SURPASS trials. The most commonly reported adverse events in SURMOUNT-OSA were gastrointestinal related and generally mild to moderate in severity. The most frequent events reported by those on tirzepatide compared with placebo, respectively, were diarrhea (26.3% vs 12.5%), nausea (25.4% vs 10.0%) and vomiting (17.5% vs 4.2%) in SURMOUNT-OSA Study 1, and diarrhea (21.8% vs 8.8%), nausea (21.8% vs 5.3%) and constipation (15.1% vs 4.4%) in SURMOUNT-OSA Study 2. Adverse events led to discontinuation of study treatment in 9 participants taking tirzepatide (5 in Study 1 and 4 in Study 2) and 10 taking placebo (2 in Study 1 and 8 in Study 2).

Tirzepatide is the only approved GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) treatment for chronic weight management, commercialized as Zepbound^® in the U.S. and Mounjaro^® in some global markets outside the US. Tirzepatide for the treatment of moderate-to-severe OSA in adults with obesity was submitted to the U.S. Food and Drug Administration (FDA) with potential approval anticipated later this year. Lilly received FDA Fast Track designation for moderate-to-severe OSA in patients with obesity.

SURMOUNT-OSA (NCT05412004) was a multi-centre, randomized, double-blind, parallel, placebo-master protocol comparing the efficacy and safety of tirzepatide to placebo in adults living with moderate-to-severe obstructive sleep apnea and obesity who were unable or unwilling to use positive airway pressure (PAP) therapy (Study 1) and those who were and planned to stay on PAP therapy during the duration of the trial (Study 2). Under a master protocol, the trials randomized 469 participants across the U.S., Australia, Brazil, China, Czechia, Germany, Japan, Mexico and Taiwan in a 1:1 ratio to receive tirzepatide maximum tolerated dose (MTD) 10 mg or 15 mg or placebo. The primary objective of both studies was to demonstrate that tirzepatide is superior in change in apnea-hypopnea index (AHI) from baseline at 52 weeks as compared to placebo.

SURMOUNT-OSA utilized a MTD of 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 maximum tolerated dose 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.

Tirzepatide is approved in Canada as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Eli Lilly and Company is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by Colonel Eli Lilly, who was committed to creating high quality medicines that meet people's needs, and today we remain true to that mission in all our work. Lilly employees work to discover and bring life-changing medicines to people who need them, improve the understanding and management of disease, and contribute to our communities through philanthropy and volunteerism.

Eli Lilly Canada was established in 1938, the result of a research collaboration with scientists at the University of Toronto which eventually produced the world's first commercially available insulin. Our work focuses on oncology, diabetes, autoimmunity, neurodegeneration, and pain. To learn more about Lilly Canada, please visit us at www.lilly.ca.

SOURCE Eli Lilly Canada Inc.