The dual GLP-1/GIP receptor agonist tirzepatide can now be used to treat the condition in some patients. See who is eligible.
Australian doctors can now prescribe tirzepatide for moderate-to-severe obstructive sleep apnoea in adults living with obesity.
The Therapeutic Goods Administration approval makes tirzepatide (Mounjaro, Eli Lilly) Australia’s first-ever registered pharmacological treatment for OSA – a move that experts have described as “a major step forward”.
The TGA expanded the indication for tirzepatide, previously approved for type 2 diabetes and weight management, following robust evidence from the pivotal SURMOUNT-OSA clinical trial, conducted across 58 sites in nine countries including Australia.
The trial investigated the efficacy of tirzepatide in patients with OSA and has showed clinically meaningful reductions in the apnoea-hypopnoea index (AHI) over a 52-week period. This trial marks the first large-scale evaluation of a pharmacological treatment for OSA that specifically targets patients both with and without concurrent positive airway pressure (PAP) therapy.
To be eligible for the treatment under the TGA’s expanded indication, patients will need to have moderate-to-severe OSA and obesity (BMI ≥30).
Tirzepatide works by mimicking two natural hormones, (glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]), and is already indicated for the management of type 2 diabetes and obesity.
Its role in the treatment of obstructive sleep apnoea is by virtue of weight reduction, easing pressure on the chest and abdomen and reducing excess fat around the neck and throat.
Professor Ron Grunstein AM, professor of Sleep Medicine at the University of Sydney and Head of the Sleep and Circadian Research Group at the Woolcock Institute of Medical Research, Macquarie University, said the news was a “long-awaited development”.
“For the first time, people with weight-related sleep apnoea can be treated with a medicine that addresses the underlying cause of their condition,” he said.
“This will establish a new standard of care for this debilitating condition.”
Current first-line treatment for obstructive sleep apnoea involves the use of a PAP machine, usually a CPAP (continuous positive airway pressure) machine. Although effective, CPAP is poorly tolerated, with up to 50% of patients abandoning usage within one year.
Professor Grunstein said that “many patients with obstructive sleep apnoea do not adhere to treatment, which can exacerbate the severity of their condition”.
“Being able to prescribe a medicine that is likely to be more acceptable to patients, and that tackles underlying and interlinked conditions, is a major step forward,” he said.
The SURMOUNT-OSA trial comprised two randomised, double-blinded, placebo-controlled phase 3 studies, one with patients using PAP therapy, the current standard of care for obstructive sleep apnoea, and the other with patients who were unwilling or unable to use PAP therapy.
Results of the trial, funded by Eli Lilly, were published in The New England Journal of Medicine last year.
In both arms, participants received tirzepatide titrated to their maximum tolerated dose (10 mg or 15 mg weekly) for one year.
In both studies, treatment demonstrated significant reductions in the primary endpoint, a clinically meaningful decrease in the AHI – a measure of how many times a person stops breathing (apnoea), or experiences reduced airflow (hypopnea) per hour during sleep.
The mean baseline AHI for PAP therapy study participants was 49.5 events per hour. This reduced to a mean of 29.3 AHI events per hour following treatment with tirzepatide – a reduction of 41%.
For participants not using PAP therapy, the mean AHI baseline was 51.5 events per hour, which fell to a mean of 25.3 AHI events per hour after treatment with tirzepatide – a reduction of more than 50%.
Participants treated with tirzepatide also saw significant improvements for all prespecified secondary endpoints, including a reduction in body weight and hypoxic burden, a measurement which captures the obstructive sleep apnoea-related risk of cardiovascular complications and death.
The safety profile of tirzepatide was consistent with that observed in previous trials, with the most frequently reported adverse events being gastrointestinal. In general these were mild-to-moderate in severity and occurred most frequently during the dose-escalation phase.
“The clinical benefits of Mounjaro in both PAP-treated and untreated patients were highly significant,” said Professor Grunstein, who was an Australian investigator for SURMOUNT-OSA.
“Improvements in apnoea and hypopnea are critically important to the health, wellbeing and quality of life of these patients.”
Professor Grunstein noted that obstructive sleep apnoea and obesity are closely linked, with at least 70% of people with the sleep condition also living with obesity.
“We know that the most effective way to treat most obstructive sleep apnoea is to address the underlying excess weight, which in turn reduces the risk of a host of complications, from type 2 diabetes to heart disease,” he said.
“In this context, the improvements noted in SURMOUNT-OSA in blood pressure, inflammation and sleep quality are clinically important. Patients often experience a vicious cycle of excessive weight and sleep apnoea, with each condition exacerbating the other.
“Having the option to prescribe a medication that may break this cycle is an important advance for patients and doctors.”
It is noted that tirzepatide is not indicated to reduce cardiovascular complications or death, or for the treatment of hypertension or inflammation.
Eli Lilly has so far been unsuccessful in gaining PBAC approval to have Mounjaro listed on the Pharmaceutical Benefits Scheme. A third reimbursement submission for the use of Mounjaro in patients with type 2 diabetes goes to the PBAC in July.
Eli Lilly’s associate vice president (medical) Dr Kevin Lim said the new indication marked an important milestone for the treatment of obstructive sleep apnoea.
“Lilly continues to invest significantly in research and innovation to find solutions to some of the greatest unmet needs in medicine, and obstructive sleep apnoea has been one of these areas,” he said in a statement.
“Our company is proud to deliver the first-ever medicine for obstructive sleep apnoea for people living with obesity and remains committed to ensuring that patients receive affordable access to Mounjaro at the earliest opportunity.”
