Obstructive Sleep Apnea and Hypertension Update: FDA Clears Phase 2 Trial of Lorundrostat, an Oral Aldosterone Synthase Inhibitor
Mineralys Therapeutics also expects topline data from its phase 2 study of lorundrostat for the treatment of uncontrolled hypertension or resistant hypertension when used as an add-on therapy.
Credit: Cleveland FES Center
The US Food and Drug Administration (FDA) has cleared Mineralys Therapeutics, Inc, to initiate a Phase 2 study evaluating lorundrostat in patients with moderate-to-severe obstructive sleep apnea (OSA) with hypertension, according to a company news release.1
The trial is expected to begin during the first quarter of 2025.
Lorundrostat is an orally administered, highly selective aldosterone synthase inhibitor designed to reduce aldosterone levels by inhibiting enzyme CYP11B2.1 The previous Phase 2 proof-of-concept trial, Target-HTN, found that lorundrostat demonstrated reductions in blood pressure in trial participants with uncontrolled or resistant hypertension. Adverse events included modest serum potassium increases and decreased estimated glomerular filtration rate.1
The company’s decision to pursue this indication is based on evidence that dysregulated aldosterone production may contribute to both hypertension and OSA by exacerbating nocturnal blood pressure surges and upper airway obstruction, Mineralys CEO Jon Congleton, said in the news release.1
“This program aligns with our strategy to develop lorundrostat in conditions driven by dysregulated aldosterone, with poor cardiovascular outcomes and few treatment options,” Congleton said. We believe suppression of aldosterone production by lorundrostat has the potential to reduce the nocturnal hypertension driving adverse cardiovascular outcomes. In addition, lorundrostat is anticipated to reduce the severity of upper airway obstruction and associated OSA symptoms such as daytime sleepiness and cognitive impairment.”1
OSA affects an estimated 54 million patients in the United States, with 30% to 50% of adults with hypertension also experiencing OSA.1 Untreated OSA is known to increase morbidity and mortality, and data suggest it can worsen resistant hypertension. Around 80% of adults with OSA are undiagnosed.1
“Obstructive sleep apnea 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,”Reena Mehra, MD, MS, a sleep disorders researcher and physician and member of the Mineralys Scientific Advisory Board, said in the company statement. “I look forward to conducting this innovative trial with Mineralys and our academic partners over the coming months.”1
The upcoming Phase 2 trial will enroll approximately 40 participants aged 18 years and older with moderate-to-severe OSA (defined as 15 or more apnea-hypopnea events per hour) and a body mass index greater than 27 kg/m2. The study will be conducted at approximately 40 sites and will use a randomized, placebo-controlled crossover design. Lorundrostat 50 mg once daily will be administered in the evening, and investigators will assess the impact on the frequency of apnea-hypopnea episodes, as well as changes in nocturnal blood pressure. Standard patient-reported outcomes specific to OSA also will be recorded.1
Mineralys announced in September 2024 that the company enrollment target of 261 subjects in its Advance-HTN trial evaluating the efficacy and safety of lorundrostat for the treatment of uncontrolled hypertension or resistant hypertension when used as an add-on therapy to a standardized background treatment of two or three antihypertensive medications. Topline data is expected in the first quarter of 2025.2
References
1. Mineralys Therapeutics announces phase 2 clinical trial of lorundrostat for obstructive sleep apnea in patients with hypertension. News release. Mineralys Therapeutics. January 8, 2025. Accessed January 17, 2025. https://ir.mineralystx.com/news-events/press-releases/detail/55/mineralys-therapeutics-announces-phase-2-clinical-trial-of
2. Mineralys Therapeutics completes target enrollment in pivotal Advance-HTN trial of lorundrostat for the treatment of hypertension. News release. September 25, 2024. Accessed January 17, 2025. https://ir.mineralystx.com/news-events/press-releases/detail/49/mineralys-therapeutics-completes-target-enrollment-in
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