The FDA has approved Eli Lilly and Company’s Zepbound (tirzepatide) as the first and only prescription medicine for adults with moderate-to-severe obstructive sleep apnoea (OSA) and obesity. The approval was based on results from the SURMOUNT-OSA phase 3 clinical trials, which evaluated Zepbound (10mg or 15mg) for the treatment of moderate-to-severe OSA in adults with obesity, with and without positive airway pressure (PAP) therapy over the course of a year.
Zepbound was about five times more effective than placebo in reducing breathing disruptions in adults not on PAP therapy, leading to 25 fewer breathing disruptions per hour with Zepbound and five with placebo. In adults on PAP therapy, Zepbound led to 29 fewer breathing disruptions per hour compared to six with placebo. After one year, 42% of adults on Zepbound and 50% of adults on Zepbound with PAP therapy experienced remission or mild, non-symptomatic OSA, compared to 16% and 14% on placebo, respectively.
In addition to improved OSA symptoms, adults on Zepbound lost an average of 45lbs (18%) of their body weight, while adults on Zepbound with PAP therapy lost an average of 50lbs (20%) of their body weight, compared to 4lbs (2%) and 6lbs (2%) on placebo, respectively.
SURMOUNT-OSA was a multi-centre, randomised, double-blind, parallel, placebo-master protocol comparing the efficacy and safety of Zepbound 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 Zepbound maximum tolerated dose (MTD) of 10mg or 15mg or placebo. The primary objective of both studies was to demonstrate that Zepbound is superior in change in apnea-hypopnea index (AHI) from baseline at 52 weeks as compared to placebo. The starting dose of 2.5mg Zepbound 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.
"Too often, OSA is brushed off as 'just snoring' - but it's far more than that," said Julie Flygare, president and CEO of Project Sleep. "It's important to understand OSA symptoms and know that treatments are available, including new options like Zepbound. We hope this will spark more meaningful conversations between patients and health care providers and ultimately lead to better health outcomes."
OSA is a sleep-related breathing disorder characterised by complete or partial collapses of the upper airway during sleep, which can lead to pauses in breathing (apnea) or shallow breathing (hypopnea) and a potential decrease in oxygen saturation and/or waking from sleep. One of the hallmarks of OSA is snoring, but fatigue, excessive daytime sleepiness and disrupted sleep are also key symptoms, making this serious condition easily overlooked.
"Today, many cases of OSA go undiagnosed and untreated, leaving millions at risk for serious health consequences," said Patrik Jonsson, executive vice president, and president of Lilly Cardiometabolic Health and Lilly USA. "Zepbound is the first medication that significantly improves moderate-to-severe OSA and aids in long-term weight loss in adults with obesity. Nearly half of clinical trial patients saw such improvements that they no longer had symptoms associated with OSA, marking a critical step forward in reducing the burden of this disease and its interconnected health challenges."