Sleep apnea, a sleep disorder typically managed with a medical device that aids in breathing, now has its first FDA-approved drug therapy, an Eli Lilly drug initially developed as a treatment for metabolic conditions.
The FDA late Friday approved Lilly's tirzepatide, brand name Zepbound, for the treatment of moderate-to-severe obstructive sleep apnea (OSA) in adults with obesity. The product's prescribing information instructs use of the once-weekly injectable mediation in combination with a reduced-calorie diet and exercise, the same as the instructions for its applications in type 2 diabetes and weight management.
OSA is caused by blockage of the upper airway that leads to pauses in breathing while a person is sleeping. Standard treatment of this chronic condition is continuous positive airway pressure, a medical device and mask worn while a patient is sleeping. The device provides constant airflow to maintain an open airway.
Sleep apnea can affect anyone, though it is more common in those with obesity or overweight. Zepbound is a peptide engineered to activate the GLP-1 and GIP receptors, which studies have shown helps regulate blood sugar. This dual mechanism of action also reduces appetite and contributes to feeling satiated, so patients eat less. It's the reduction in body weight that is thought to improve sleep apnea.
Zepbound's sleep apnea approval is based on the results of two double-blind, placebo-controlled Phase 3 tests that enrolled 469 adults without type 2 diabetes. In one of the studies, participants used CPAP. The other study enrolled those unable or unwilling to use the medical device. The main goal was to show change according to the apnea hypopnea index, a rating scale used measure how often a person stops breathing or breathes shallowly per hour.
Results showed that after 52 weeks, participants treated with Zepbound achieved a statistically significant and clinically meaningful reduction in breathing disruptions per hour compared to those who received a placebo. The data also showed that participants in the Zepbound cohorts lost between 18% and 20% of their body weight compared to the placebo groups. The most common side effects reported in the sleep apnea study were gastrointestinal in nature, and included nausea and diarrhea. These adverse effects are known complications of Zepbound and others in the same class of drugs that mimic gut hormones.
When Lilly posted preliminary data from the sleep apnea study in April, the stock prices of companies such as Inspire Medical Systems, which makes CPAP devices, took a hit. Zepbound's latest approval poses a new competitive challenge to such companies. In a research note sent to investors Sunday, Leerink Partners analyst Mike Kratky said Zepbound was approved for OSA without any requirement that patients fail or refuse CPAP treatment, which means the drug can be used as a front-line therapy for eligible patients. But Kratky also noted that clinicians have told Leerink that treatment with CPAP and Zepbound concurrently may be an even more efficacious front-line approach to OSA.
Tirzepatide first reached patients in 2022 with FDA approval of the medication as a treatment for type 2 diabetes. The drug is marketed in this indication under the brand name Mounjaro. Zepbound, a lower dose of tirzepatide, was approved last year for chronic weight management. The drug, in both of its approved versions, has quickly become a top Lilly product. In the first nine months of this year, Mounjaro accounted for more than $8 billion in revenue while Zepbound tallied $3 billion in sales.
Sleep apnea, which affects an estimated 25 million adults in the U.S., gives Lilly the opportunity to add another indication with blockbuster potential. More applications could be coming for the drug. Lilly's tirzepatide clinical research includes the fatty liver disease metabolic dysfunction-associated steatohepatitis (MASH) as well as cardiovascular indications.
"Zepbound is the first medication that significantly improves moderate-to-severe OSA and aids in long-term weight loss in adults with obesity," Patrik Jonsson, executive vice president, and president of Lilly Cardiometabolic Health and Lilly USA, said in a prepared statement. "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."