Eli Lilly and Company announced positive topline results of the SURMOUNT-OSA phase 3 clinical trials that showed tirzepatide injection (10 mg or 15 mg) significantly reduced the apnea-hypopnea index (AHI) compared to placebo, achieving the primary endpoints. Percentage change in AHI was a key secondary endpoint in both studies. AHI records the number of times a person's breathing shows a restricted or complete block of airflow per hour of sleep and is used to evaluate the severity of obstructive sleep apnea (OSA) and the effectiveness of treatment outcomes. 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 U.S.
SURMOUNT-OSA Study 1 evaluated tirzepatide in adults with moderate-to-severe OSA and obesity who were not on positive airway pressure (PAP) therapy for 52 weeks. For the efficacy estimandi, at 52 weeks, tirzepatide led to a mean AHI reduction from baseline of 27.4 events per hour compared to a mean AHI reduction from baseline of 4.8 events per hour for placebo. In key secondary outcomes, tirzepatide led to a mean AHI reduction from baseline of 55.0% compared to 5.0% from baseline for placebo; tirzepatide also led to a mean body weight reduction of 18.1% from baseline, compared to 1.3% from baseline for placebo.
SURMOUNT-OSA Study 2 evaluated tirzepatide in adults with moderate-to-severe OSA and obesity who were on and planned to continue to use PAP therapy for 52 weeks. In this population for the efficacy estimand, at 52 weeks, tirzepatide led to a mean AHI reduction from baseline of 30.4 events per hour compared to a mean AHI reduction from baseline of 6.0 events per hour for placebo. In key secondary outcomes, tirzepatide led to a mean AHI reduction from baseline of 62.8% compared to 6.4% from baseline for placebo; tirzepatide also led to a mean body weight reduction of 20.1% from baseline, compared to 2.3% from baseline for placebo.
The weight loss observed at 52 weeks with tirzepatide (10 mg and 15 mg) across the two studies was nearly 20% in a patient population that was comprised of approximately 70% males, who are known to achieve less weight loss with incretin therapy than females.
OSA is a sleep-related breathing disorder characterized by complete or partial collapses of the upper airway during sleep, which can lead to apnea or hypopnea and a potential decrease in oxygen saturation and/or waking from sleep. OSA can have serious cardiometabolic complications, contributing to hypertension, coronary heart disease, stroke, heart failure, atrial fibrillation and type 2 diabetes.
"OSA impacts 80 million adults in the U.S., with more than 20 million living with moderate-to-severe OSA. However, 85% of OSA cases go undiagnosed and therefore untreated," said Jeff Emmick, MD, Ph.D., senior vice president, product development, Lilly. "Addressing this unmet need head-on is critical, and while there are pharmaceutical treatments for the excessive sleepiness associated with OSA, tirzepatide has the potential to be the first pharmaceutical treatment for the underlying disease."
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 commonly reported adverse events for patients treated with tirzepatide were diarrhea, nausea and vomiting in SURMOUNT-OSA Study 1, and diarrhea, nausea and constipation in SURMOUNT-OSA Study 2.
SURMOUNT-OSA trials will be presented during a symposium at the American Diabetes Association's 84th Scientific Sessions on June 21 at 3:45 p.m. ET and submitted to a peer-reviewed journal. Based on these results, Lilly plans to submit to the U.S. Food and Drug Administration (FDA) and other global regulatory agencies beginning mid-year. Lilly received FDA Fast Track designation for moderate-to-severe OSA and obesity.
