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Mineralys Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on developing medicines to target hypertension, chronic kidney disease (CKD) and other diseases driven by dysregulated aldosterone, announced that the US Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for a phase 2 clinical trial to evaluate the effect of lorundrostat in the treatment of subjects with moderate-to-severe obstructive sleep apnoea (OSA) and hypertension. The company anticipates initiating the trial in the first quarter of 2025.
“We are pleased to announce the OSA clinical development program for lorundrostat. This program aligns with our strategy to develop lorundrostat in conditions driven by dysregulated aldosterone, with poor cardiovascular outcomes and few treatment options,” stated Jon Congleton, chief executive officer of Mineralys Therapeutics. “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.”
“Obstructive sleep apnoea 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,” stated Reena Mehra, MD, MS, a sleep disorders researcher and physician and new member of the Mineralys Scientific Advisory Board. “We designed the OSA trial in collaboration with a group of thought leaders in sleep apnoea treatment in order to incorporate state-of-the-art technology, register sites with expertise in sleep medicine, and pinpoint the right participants to ensure high-quality data that are reflective of real-world unmet needs facing these patients. I look forward to conducting this innovative trial with Mineralys and our academic partners over the coming months.”
The planned phase 2 clinical trial is a placebo-controlled, crossover study to evaluate the safety and efficacy of lorundrostat 50mg taken once daily in the evening in approximately 40 subjects with moderate-to-severe OSA. Subjects will be at least 18 years old, with a BMI =27 kg/m2, and the trial will be conducted across approximately 40 sites.
The key objective of this trial is to validate the hypothesis that lorundrostat both alleviates the severity of upper airway obstruction and reduces nocturnal hypertension. The primary outcome measure is absolute change in the frequency of apnoea-hypopnea episodes. The key secondary objective is to quantify blood pressure throughout the night using continuous BP monitoring during performance of a standard sleep study without the benefit of CPAP. Standard patient reported outcomes, specific to OSA will also be assessed.
The company believes that its current cash, cash equivalents and investments will be sufficient to fund its planned clinical trials, and support its corporate operations through the first quarter of 2026.
Obstructive sleep apnoea (OSA) is characterized by repetitive overnight hypoxic episodes and subsequent sleep fragmentation due to a complete or partial collapse of the upper airway. Moderate OSA is defined as having between 15 and 30 breathing pauses (apnoea or hypopnea events) per hour of sleep, while severe OSA indicates more than 30 breathing pauses per hour. OSA impacts almost one billion people globally, including 425 million moderate-to-severe cases. Around 80% of adults with OSA are undiagnosed. As of 2015, undiagnosed OSA is estimated to cost the United States approximately $149.6 billion annually from comorbid disease, workplace accidents, motor vehicle accidents and loss of workplace productivity.
Between 30-50% of adults with hypertension have OSA, and this number increases to between 70-80% in adults with resistant hypertension. Additionally, untreated moderate-to-severe OSA increases the risk of resistant hypertension. Along with hypertension, OSA is a major risk factor of cardiovascular disease, type-2 diabetes mellitus and stroke.
Lorundrostat is a proprietary, orally administered, highly selective aldosterone synthase inhibitor being developed for the treatment of uncontrolled hypertension (uHTN) and resistant hypertension (rHTN) as well as chronic kidney disease (CKD). Lorundrostat was designed to reduce aldosterone levels by inhibiting CYP11B2, the enzyme responsible for its production. Lorundrostat has 374-fold selectivity for aldosterone-synthase inhibition versus cortisol-synthase inhibition in vitro, an observed half-life of 10-12 hours and demonstrated approximately a 70% reduction in plasma aldosterone concentration in hypertensive subjects.
In a phase 2, proof-of-concept trial (Target-HTN) in uncontrolled or resistant hypertensive subjects, once-daily lorundrostat demonstrated clinically meaningful blood pressure reduction in both automated office blood pressure measurement and 24-hour ambulatory blood pressure monitoring. Adverse events observed were a modest increase in serum potassium, decrease in estimated glomerular filtration rate, urinary tract infection and hypertension with one serious adverse event possibly related to study drug being hyponatremia.
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