Mineralys Therapeutics, Inc. (Nasdaq: MLYS) has announced the advancement of lorundrostat, a selective aldosterone synthase inhibitor, into a Phase 2 clinical trial for the treatment of moderate-to-severe obstructive sleep apnea (OSA) in patients with hypertension. The U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application, paving the way for the trial's initiation in the first quarter of 2025.
The Phase 2 trial is designed as a placebo-controlled, crossover study involving approximately 40 subjects with moderate-to-severe OSA and a BMI of 27 kg/m2 or higher. Participants will receive 50mg of lorundrostat once daily in the evening. The primary objective is to evaluate the drug's efficacy in alleviating upper airway obstruction and reducing nocturnal hypertension, common in OSA patients. The primary outcome measure will be the absolute change in the frequency of apnea-hypopnea episodes, with continuous blood pressure monitoring during sleep studies serving as a key secondary objective.
Rationale for Lorundrostat in OSA
Jon Congleton, Chief Executive Officer of Mineralys Therapeutics, stated, "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."
Reena Mehra, MD, MS, a sleep disorders researcher and member of the Mineralys Scientific Advisory Board, emphasized the physiological and psychological impacts of OSA, noting the surges in blood pressure overnight that contribute to daytime hypertension. She highlighted the collaborative design of the trial, incorporating state-of-the-art technology and expertise in sleep medicine to ensure high-quality data reflective of real-world unmet needs.
Addressing Unmet Needs in OSA Treatment
Obstructive sleep apnea affects an estimated 54 million people in the U.S., with 30-50% of adults with hypertension also suffering from OSA. The condition is characterized by repetitive overnight hypoxic episodes and sleep fragmentation due to upper airway collapse. Current treatments, such as CPAP, face compliance issues and do not always address the elevated nighttime blood pressure associated with OSA.
Lorundrostat: A Selective Aldosterone Synthase Inhibitor
Lorundrostat is a proprietary, orally administered, highly selective aldosterone synthase inhibitor designed to reduce aldosterone levels by inhibiting CYP11B2, the enzyme responsible for its production. It has demonstrated approximately 70% reduction in plasma aldosterone concentration in hypertensive subjects. In a Phase 2 trial (Target-HTN), lorundrostat showed clinically meaningful blood pressure reduction in uncontrolled or resistant hypertensive subjects.
Explore-CKD Trial Completion
Mineralys Therapeutics also announced the completion of enrollment in the Explore-CKD Phase 2 trial. This trial evaluates the efficacy and safety of lorundrostat for treating hypertension in subjects with Stage 2 to 3b chronic kidney disease (CKD) and albuminuria, who are already receiving stable treatment with an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) and an SGLT2 inhibitor. Topline data from the Explore-CKD trial is anticipated in the second quarter of 2025.
Financial Outlook
Mineralys Therapeutics believes its current cash, cash equivalents, and investments will be sufficient to fund planned clinical trials and support corporate operations through the first quarter of 2026.
