Eli Lilly and Company has announced positive topline results from the SURMOUNT-OSA phase 3 clinical trials that showed tirzepatide injection (10mg or 15mg) significantly reduced the apnoea-hypopnea index (AHI) compared to placebo, achieving the primary endpoints. 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 OSA and the effectiveness of treatment outcomes. Percentage change in AHI was a key secondary endpoint in both studies.
SURMOUNT-OSA 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 OSA 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 US, Australia, Brazil, China, Czechia, Germany, Japan, Mexico and Taiwan in a 1:1 ratio to receive tirzepatide maximum tolerated dose (MTD) 10mg or 15mg or placebo. The primary objective of both studies was to demonstrate that tirzepatide is superior in change in AHI from baseline at 52 weeks as compared to placebo.
SURMOUNT-OSA utilised a MTD of 10mg or 15mg once-weekly. The starting dose of 2.5mg tirzepatide was increased by 2.5mg every four weeks until maximum tolerated dose was achieved. Participants who tolerated 15mg continued on 15mg as their MTD. Participants who tolerated 10mg but did not tolerate 15mg continued on 10mg as their MTD.
SURMOUNT-OSA Study 1 evaluated tirzepatide in adults living 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 (10mg and 15mg) 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 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 Dr Jeff Emmick, 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 diarrhoea, nausea and vomiting in SURMOUNT-OSA Study 1, and diarrhoea, 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 in June and submitted to a peer-reviewed journal. Based on these results, Lilly plans to submit to the FD and other global regulatory agencies beginning mid-year.
Tirzepatide is the only approved GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) treatment for chronic weight management, commercialised as Zepbound in the US and Mounjaro in some global markets.