The Brief

A European clinical trial published in The Lancet found that the epilepsy drug sulthiame reduced breathing interruptions by up to 47 percent in patients with moderate-to-severe obstructive sleep apnea. The Phase 2 study, involving 298 patients across five countries over 15 weeks, showed dose-dependent improvements in overnight oxygenation and daytime sleepiness, with mostly mild side effects.

The Report

An existing anti-seizure medication has produced the strongest pharmacological result to date against obstructive sleep apnea, a condition estimated to affect more than 80 million Americans and nearly one billion people worldwide.

The Phase 2 FLOW trial, conducted across 28 sites in Spain, France, Belgium, Germany, and the Czech Republic, randomised 298 adults with untreated moderate-to-severe sleep apnea into four groups: three dosage tiers of sulthiame — 100 mg, 200 mg, and 300 mg — and a placebo. Over 15 weeks, the study met its primary endpoint across all doses, with reductions in the apnea-hypopnea index of 17.8 percent at the lowest dose, 34.8 percent at the middle dose, and 39.9 percent at the highest. A secondary measure using a stricter oxygen desaturation threshold showed reductions approaching 50 percent.

Patients in the treatment groups also showed improved blood oxygen levels during sleep and reported less daytime drowsiness. Side effects — primarily paraesthesia, headache, fatigue, and nausea — were generally mild or moderate and increased with dose.

Sulthiame, originally developed in the 1960s by Bayger AG as an anticonvulsant, is still prescribed for childhood epilepsy in several European countries but has never been approved in the United States. It works by inhibiting carbonic anhydrase, an enzyme involved in respiratory regulation, and by stimulating upper airway muscles — addressing the mechanical collapse that causes apnea episodes. US-based biotech Apnimed, which acquired global rights to the drug from Germany’s Desitin Arzneimittel, is developing it in partnership with Japan’s Shionogi through a joint venture.

Jan Hedner, senior professor of pulmonary medicine at the University of Gothenburg and the study’s lead researcher, described the results as a breakthrough. “We have been working on this treatment strategy for a long time, and the results show that sleep apnea can indeed be influenced pharmacologically,” he said. He noted that Phase 3 trials are still needed to confirm the findings in larger patient populations.

The current standard of care remains CPAP — continuous positive airway pressure machines that keep airways open with forced air through a face mask. Up to half of CPAP patients abandon the device within a year. Adherence rates have shown no meaningful improvement in two decades of data despite behavioural interventions. Apnimed is separately pursuing AD109, a different drug combination already through Phase 3 trials, with an FDA submission planned for early 2026. Eli Lilly’s injectable tirzepatide became the first FDA-approved drug for moderate-to-severe sleep apnea in late 2024, though it works indirectly through weight loss.

The study was published in The Lancet. Sulthiame remains at least one full trial phase from potential regulatory approval for sleep apnea.

The Angle

The most cited number in the coverage — 47 percent — is worth pausing on for what it reveals about the condition rather than the drug. A treatment that cuts apnea episodes nearly in half is genuinely significant. It is also, by definition, a treatment that leaves the other half of the episodes intact. This is not a cure. It is a meaningful reduction in a disease that currently has one serious intervention and a compliance rate that would be considered a crisis in any other therapeutic area.

That compliance figure is the buried story. Half of all CPAP patients stop using the device within a year. The number has not improved in twenty years. Two decades of behavioural nudges, mask redesigns, and patient education programmes have moved the needle on adherence by approximately nothing. In most fields of medicine, a flagship treatment with a 50 percent long-term dropout rate would prompt a fundamental reassessment of the approach. In sleep medicine, it prompted two decades of asking how to make patients tolerate the approach better. The question of whether a mechanical splint applied nightly for life was the right category of solution was, until very recently, barely being asked at a level that attracted serious funding.

What changed is not a single trial. It is that multiple pharmaceutical companies — Apnimed with two separate drug candidates, Eli Lilly with an injectable, Incannex with a third mechanism — have converged on the same conclusion simultaneously: the airway problem might be better addressed chemically than mechanically. The FLOW trial is Phase 2. The road to approval is long. But the shift it represents — from engineering around a dysfunction to treating the dysfunction itself — is the development that the billion people living with collapsing airways have been waiting for, whether or not this particular molecule is the one that gets there.