Trials set up filing for Lilly’s tirzepatide in sleep apnoea

Eli Lilly’s diabetes and obesity therapy tirzepatide could find a use as a treatment for obstructive sleep apnoea (OSA) after hitting the mark in a pair of phase 3 trials.

OSA is a prevalent sleep-disordered breathing with potentially serious long-term effects, that is most common in people who are overweight and affects millions of people in the US. It results in repeated interruptions in breathing during sleep caused by narrowing and collapse of the airway.

Untreated, it can lead to serious complications such as heart attack, glaucoma, diabetes, cancer, and cognitive and behavioural disorders.

Tirzepatide – sold as Mounjaro for diabetes and Zepbound for obesity – has been shown in the SURMOUNT-OSA trials to reduce sleep apnoea severity by up to nearly two-thirds in adults with OSA and moderate-to-severe obesity, setting up regulatory filings around the world from the middle of this year.

The dual GLP-1 and GIP agonist reduced the apnoea-hypopnoea index (AHI) by up to 63% at 52 weeks, which Lilly said was equivalent to around 30 fewer breathing interruptions per hour.

SURMOUNT-OSA Study 1 recruited patients with OSA who were not on positive airway pressure (PAP) therapy, in which a mask is worn during sleep that blows air into the lungs and keeps the airway open. In this group, the average AHI reduction was 27.4 events per hour compared to 4.8 with placebo after a year.

SURMOUNT-OSA Study 2 involved patients who needed PAP therapy and in this group tirzepatide achieved an average AHI reduction of 30.4 events per hour, versus 6.0 for the control group.

Treatment in both studies also led to weight reductions in the population of mostly male patients of 18% to 20%, which Lilly said was a notable result as GLP-1 agonists are known to be less effective at reducing weight in men.

“OSA impacts 80 million adults in the US, with more than 20 million living with moderate-to-severe OSA,” said Jeff Emmick, Lilly’s head of product development. However, he added that a huge majority (around 85%) of OSA cases go undiagnosed and therefore untreated.

“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.”

Adding OSA to the label for tirzepatide could give a boost to the drug in what is becoming a fiercely competitive GLP-1 agonist or ‘incretin’ market, in which Lilly is already squaring off with Novo Nordisk and others, with a lengthening list of new therapies coming through development for diabetes, obesity, and other indications.

So far, Novo Nordisk has not explored the use of its GLP-1 agonist semaglutide for OSA, although, like Lilly it already has approvals in cardiovascular disease and chronic kidney disease and is looking at various other indications, including Alzheimer’s disease and metabolic dysfunction-associated steatohepatitis (MASH).

Crucially, extending the label of Zepbound to include OSA could make it easier for Lilly to secure coverage of the drug through Medicare and private insurers that won’t cover it for obesity alone.

Photo by Max van den Oetelaar on Unsplash