Topline results from the exploratory trial indicate the aldosterone synthase inhibitor did not reduce the apnea-hypopnea index but provided clinically meaningful blood pressure reduction in adults with moderate-to-severe OSA and hypertension.

Key takeaways:

The phase 2 Explore-OSA trial evaluated lorundrostat in 48 overweight or obese adults with moderate-to-severe obstructive sleep apnea and hypertension.
After four weeks, the 50 mg evening dose did not demonstrate a clinically meaningful difference relative to placebo on the primary endpoint of reducing the AHI.
The trial did show a clinically meaningful reduction in blood pressure, with an 11.1 mmHg reduction compared to a 1.0 mmHg reduction for placebo in the first period parallel arm analysis.
Lorundrostat was well tolerated with a favorable safety profile and no serum potassium excursions above 5.5 mmol/L.

Mineralys Therapeutics announced topline results from its phase 2 Explore-OSA exploratory trial, evaluating the efficacy and safety of lorundrostat in overweight or obese adults with moderate-to-severe obstructive sleep apnea (OSA) and hypertension.

The trial involved 48 participants with an average body mass index of 38.2 kg/m2, an average apnea-hypopnea index (AHI) of 48.5 events per hour, and an average systolic blood pressure of 142.3 mmHg. After four weeks of treatment, lorundrostat 50 mg dosed in the evening did not demonstrate a clinically meaningful difference relative to placebo on the AHI, which was the trial’s primary endpoint.

However, the trial did demonstrate significant blood pressure reductions in this population. At week four, the trial showed an 11.1 mmHg reduction in blood pressure with lorundrostat compared to a 1.0 mmHg reduction with placebo in the pre-planned parallel arm analysis of the first period. Additionally, there was a 6.2 mmHg placebo-adjusted reduction in blood pressure in the crossover analysis.

“While the Explore-OSA trial did not demonstrate a reduction in AHI, the blood pressure reductions and safety profile were clinically meaningful, especially for this difficult-to-control population,” says Jon Congleton, chief executive officer of Mineralys Therapeutics, in a release. “We believe lorundrostat has the potential to become an important new treatment option for resistant and uncontrolled hypertension, and we look forward to working with the FDA as we advance toward potential approval.”

Lorundrostat demonstrated a favorable safety profile and was well tolerated, with no serum potassium excursions above 5.5 mmol/L. The drug is a proprietary, orally administered, highly selective aldosterone synthase inhibitor. According to Mineralys Therapeutics, moderate to severe OSA is associated with increased production of aldosterone and increased nighttime blood pressure, and standard treatment with positive airway pressure is often not sufficient for blood pressure reduction in these patients.

Between 30% and 50% of adults with hypertension have OSA, and this number increases to between 70% and 80% in adults with resistant hypertension.

In related news, the US Food and Drug Administration (FDA) has accepted the New Drug Application for lorundrostat for the treatment of adult patients with hypertension in combination with other antihypertensive drugs, assigning a target action date of December 22, 2026.

Analysis is ongoing for other secondary endpoints in the Explore-OSA trial, including nighttime blood pressure and sleep and cardiovascular health measures, which will be reported in future publications or medical meetings.