Sulthiame shows potential as a drug treatment for OSA

medwireNews: Research presented at the ERS Congress 2024 supports sulthiame 200 or 300 mg as a drug therapy for obstructive sleep apnea (OSA), showing it consistently reduces sleep disordered breathing and improves sleep quality. Jan Hedner (Gothenburg University, Sweden) presented the findings to delegates in Vienna, Austria, explaining that the carbonic anhydrase inhibitor has previously been shown to reduce OSA activity in a proof-of-concept study (STM-026/K). In an extension to this, they compared sulthiame at one of three doses – 100 mg, 200 mg, and 300 mg – with placebo over a 15-week treatment period. In all, 298 patients from 33 centres in five European countries, who had not accepted or tolerated continuous positive airway pressure or oral splints, were randomly assigned. They had a mean age of 56.1 years, 73.8% were men, and the baseline BMI was a mean of 29.1 kg/m2. The primary efficacy endpoint of relative change in apnea-hypopnea index (AHI) with a 3% or greater fall in oxyhemoglobin saturation or an event-related arousal was met at 15 weeks. Specifically, the placebo-adjusted reductions from a mean baseline rate of 29.0% were a significant 17.8% in the 74 patients taking sulthiame at the 100 mg dose, 34.8% among the 74 patients taking the 200 mg dose, and 39.9% for the 75 patients taking the 300 mg dose. “Peak efficacy was in the 200–300 mg range and there was a similar effect in both moderate and severe OSA,” Hedner said. Indeed, he reminded the audience that “these are completely unselected patients, they are not preselected for any specific characteristic that would make them more or less suitable for a study like this.” There were also significant reductions in AHI with 4% or greater fall in oxyhemoglobin saturation. This was a mean of 16.6% at baseline and after 15 weeks of sulthiame treatment, it had fallen by a mean of 26.2%, 36.8%, and 47.1% in patients taking the 100, 200, and 300 mg doses, respectively. In parallel to these findings, the presenter reported that overnight oxygen saturation improved significantly among the patients taking the higher two doses. There was a mean reduction from baseline on the 3% oxygen desaturation index (ODI) of 5.5% and 6.5% with sulthiame 200 and 300 mg, respectively, relative to placebo, and corresponding mean increases in arterial oxygen saturation of 0.95% and 0.87%. The relative changes on these outcomes did not reach statistical significance with the 100 mg dose. Sleep quality, measured on the Total Arousal Index, was significantly improved with placebo-adjusted reductions from baseline of 3.1%, 5.7%, and 6.7%, with sulthiame 100, 200, and 300 mg, respectively. In addition, Hedner reported an improvement in sleepiness for all patients taking sulthiame, as measured on the Epworth Sleepiness scale (ESS), with a mean 1.3–1.8-point reduction in scores compared with 0.9 points with placebo, and this was particularly evident among the subgroup of “sleepy” patients who had a baseline ESS score of at least 11 points and achieved a reduction of 2.7–3.5 points versus 1.1 points with placebo. The presenter highlighted an “additive effect” in terms of blood-pressure (BP) lowering, with a 3.0–4.0 mmHg decrease in systolic BP among patients taking sulthiame 200 or 300 mmHg and a reduction in diastolic BP in the region of 2.5 mmHg with either dose. He said they were “surprisingly happy with” this BP-lowering signal given that the participants were normotensive or receiving appropriate antihypertensive medication. Discussing the safety profile of the drug, Hedner said that sulthiame was “proportionally well-tolerated,” and while they expected side effects to increase with the higher doses, they did not do so “severely.” As expected, paresthesia was the most common side effect, occurring in 21.6–57.3% of patients across the sulthiame treatment arms, compared with 9.3% of those in the placebo arm. However, the researcher said that “it was quite mild,” and “wasn’t really limiting in this study,” adding that “people don’t quit the study simply because they have parathesia.” He concluded that sulthiame is a “promising candidate” for drug treatment of OSA and will now be tested in phase 3 trials. medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group ERS Congress 2024; Vienna, Austria: 7–11 September

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Sulthiame shows potential as a drug treatment for OSA

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