Mineralys Therapeutics has received FDA clearance for a phase II clinical trial investigating lorundrostat, an aldosterone synthase inhibitor, in patients with moderate-to-severe obstructive sleep apnea and hypertension. The trial is expected to begin in Q1 of 2025.
The placebo-controlled, crossover study will evaluate lorundrostat 50 mg taken once daily in approximately 40 patients across 40 sites. Eligible participants must be at least 18 years old with a body mass index ≥ 27 kg/m2.
The trial's primary endpoint will measure absolute change in apnea-hypopnea episode frequency. A key secondary endpoint will assess nocturnal blood pressure via continuous monitoring during standard sleep studies without continuous positive airway pressure intervention.
"Obstructive sleep apnea [OSA] carries significant physiological and psychological impacts on health. Along with trouble sleeping, excessive daytime sleepiness and snoring from repetitive upper airway closure, patients frequently experience significant surges in blood pressure overnight contributing to the daytime hypertension that most are struggling to control," explained Reena Mehra, MD, MS, a sleep disorders researcher and new member of the Mineralys Scientific Advisory Board.
The drug candidate has demonstrated selectivity in previous studies, with a 374-fold preference for aldosterone-synthase inhibition vs cortisol-synthase inhibition in vitro. It has shown an observed half-life of 10 to 12 hours and achieved approximately 70% reduction in plasma aldosterone concentration in hypertensive patients.
Earlier phase II data in uncontrolled or resistant hypertension showed clinically meaningful blood pressure reductions in both automated office measurements and 24-hour ambulatory monitoring. Reported adverse events included modest increases in serum potassium, decreased estimated glomerular filtration rate, urinary tract infection, hypertension, and one serious adverse event of hyponatremia possibly related to the study drug.
The trial's hypothesis posits that lorundrostat may both alleviate upper airway obstruction severity and reduce nocturnal hypertension. This represents Mineralys' third precision indication for lorundrostat in aldosterone-driven diseases.
The medical need is substantial: OSA affects an estimated 54 million U.S. patients, including 30% to 50% of adults with hypertension. In patients with resistant hypertension, OSA prevalence increases to 70% to 80%. Untreated moderate-to-severe OSA raises the risk of resistant hypertension and serves as a major risk factor for cardiovascular disease, type 2 diabetes mellitus, and stroke.
The company reported having sufficient funding through Q1 2026 to support its planned clinical trials and operations.
Reference:
Mineralys Therapeutics. Mineralys Therapeutics announces Phase 2 clinical trial of lorundrostat in individuals with chronic kidney disease. Mineralys Therapeutics website. https://ir.mineralystx.com/news-events/press-releases/detail/55/mineralys-therapeutics-announces-phase-2-clinical-trial-of