A large European clinical trial published in The Lancet has found that sulthiame, an existing medication used to treat childhood epilepsy, reduced breathing interruptions during sleep by up to 47% in patients with moderate to severe obstructive sleep apnea.
The findings, which were announced this week by Apnimed, bring the sleep medicine field closer to what has long been considered a holy grail: a pill that treats the underlying cause of obstructive sleep apnea rather than just managing symptoms with a mask.
The FLOW Trial
The study, called FLOW, was a multicenter, randomized, double-blind, placebo-controlled trial conducted across 28 sites in five European countries. Researchers enrolled 298 adults with untreated moderate to severe obstructive sleep apnea and tested three dosages of sulthiame—100 mg, 200 mg, and 300 mg—administered once daily at bedtime for 15 weeks. One quarter of participants received a placebo.
The results were striking. Patients taking the higher doses experienced approximately 30 to 50% fewer breathing interruptions during sleep compared to the placebo group. Oxygen levels during sleep also improved significantly, as did mean oxygen saturation throughout the night.
How Sulthiame Works
Unlike CPAP machines that physically hold the airway open with pressurized air, sulthiame appears to work by stabilizing the body's control of breathing and increasing respiratory drive. This helps lower the likelihood that the upper airway will collapse during sleep, which is the primary mechanism behind obstructive sleep apnea.
The drug belongs to a class of medications called carbonic anhydrase inhibitors, and it has been safely used for decades to treat a form of childhood epilepsy called benign rolandic epilepsy.
The results raise the possibility of a drug treatment for patients who struggle to tolerate breathing masks, which could transform how we approach obstructive sleep apnea.
Finding the Right Dose
While the 300 mg dose produced the largest reduction in breathing interruptions, researchers noted that side effects increased with dosage. The 200 mg dose appeared to be the sweet spot, balancing meaningful clinical improvement with a manageable side effect profile.
No clinically relevant safety concerns were identified at any dose during the 15-week trial period, though longer-term studies will be needed to establish the drug's safety for chronic use.
Why a Pill Matters
Despite being the gold standard treatment for obstructive sleep apnea, CPAP therapy has a well-documented adherence problem. Studies consistently show that roughly half of patients abandon their CPAP machines within the first year, primarily because they find the mask uncomfortable, claustrophobic, or disruptive to sleep.
This leaves millions of people with untreated sleep apnea, putting them at elevated risk for cardiovascular disease, stroke, diabetes, and cognitive decline.
An effective oral medication could reach patients who:
- Cannot tolerate CPAP despite trying multiple mask styles and pressure settings
- Travel frequently and find CPAP equipment burdensome
- Have mild to moderate cases that may not warrant nightly mask therapy
- Want a complementary treatment to use alongside reduced CPAP pressure
A Growing Pipeline
Sulthiame joins an increasingly active pipeline of pharmaceutical approaches to sleep apnea. Apnimed's own AD109 (branded as LunAIRo) completed Phase 3 trials and is expected to seek FDA approval, while GLP-1 drugs originally developed for diabetes and weight loss have also shown promise in reducing sleep apnea severity.
Researchers at the University of Gothenburg, who were involved in the FLOW trial, described the results as evidence that a first drug treatment for sleep apnea is now within reach.
What Comes Next
The Phase 2 results are promising but preliminary. Larger Phase 3 trials will be needed to confirm sulthiame's efficacy and safety before it could receive regulatory approval for treating sleep apnea. Those trials will likely test the drug in more diverse patient populations and over longer treatment periods.
For now, CPAP remains the primary treatment for obstructive sleep apnea, and patients should not stop using their prescribed therapy. But for the millions who have struggled with CPAP or abandoned it altogether, the prospect of a nightly pill is closer than ever.
