New findings reveal lorundrostat significantly lowers blood pressure and albuminuria in patients with chronic kidney disease, enhancing standard treatment efficacy.
Late-breaking data presented at the American Society of Nephrology (ASN) Kidney Week 2025 demonstrate that, when added to standard-of-care therapy, 25 mg of lorundrostat (Mineralys Therapeutics) demonstrated statistically significant and clinically meaningful reductions in blood pressure and albuminuria in patients with chronic kidney disease (CKD) and uncontrolled hypertension. The findings from the phase 2 Explore-CKD (NCT06150924) clinical trial further support the use of lorundrostat in this patient population.1,2
Trial Name: Efficacy and Safety of Lorundrostat in Addition to Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) in Subjects with Hypertension and Chronic Kidney Disease (CKD) with Albuminuria
ClinicalTrials.gov ID: NCT06150924
Sponsor: Mineralys Therapeutics Inc.
Completion Date: April 23, 2025
Lorundrostat is a proprietary, orally administered, highly selective aldosterone synthase inhibitor that is under development for the treatment of CKD, obstructive sleep apnea, and both uncontrolled hypertension and resistant hypertension. Lorundrostat reduces aldosterone levels by inhibiting CYP11B2, the enzyme responsible for its production, and has been shown to have a 374-fold selectivity for aldosterone-synthase inhibition vs cortisol-synthase inhibition in vitro. It has an observed half-life of 10 to 12 hours and demonstrated a 40% to 70% reduction in plasma aldosterone concentration in hypertensive participants, according to experts.1,3
Explore-CKD is a randomized, placebo-controlled, crossover trial that evaluated the efficacy of 25 mg of lorundrostat when added to a sodium-glucose cotransporter 2 (SGLT2) inhibitor and an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker in patients with CKD. The enrolled patients had an estimated glomerular filtration rate (eGFR) of 30 mL/min/1.73 m2 and albuminuria (urine albumin-to-creatinine ratio [UACR] of 200–5000 mg/g).1-3
Explore-CKD’s primary efficacy end point was the change from baseline in systolic blood pressure at week 4 in the active vs placebo treatment period. Additional exploratory end points included change from baseline in UACR and eGFR at week 4 in the active vs placebo treatment period, according to the trial investigators.1-3
A late-breaking presentation on the Explore-CKD trial of a once-daily 25-mg lorundrostat dose added to standard-of-care therapy, including SGLT2 inhibitors, demonstrated statistically significant and clinically meaningful reductions in blood pressure and albuminuria in participants with uncontrolled hypertension and CKD at 4 weeks of treatment. Specifically, the trial met its primary end point, showing a reduction of about 9.3 mm Hg in automated office systolic blood pressure and a placebo-adjusted reduction of 7.5 mm Hg (P = .0024) at week 4. Additionally, lorundrostat also achieved a reduction in spot UACR of 25.6% placebo-adjusted reduction (P = .0015) at week 4.1 These findings are supported by previous data from June 2025.3
“The presentations at ASN Kidney Week demonstrated the breadth and strength of lorundrostat’s clinical program. As previously announced, the compelling results from multiple trials in this program have positioned us well for the planned filing of a new drug application to the FDA in the fourth quarter of 2025 or the first quarter of 2026,” Jon Congleton, CEO of Mineralys Therapeutics, said in a news release. “In Explore-CKD, lorundrostat reduced both blood pressure and albuminuria in participants with CKD. We are pleased that the significant and consistent blood pressure reduction previously reported with lorundrostat.... With consistent benefits across blood pressure and kidney outcomes, lorundrostat is uniquely positioned to address the growing burden of cardio-renal-metabolic disease.”1
During the trial, lorundrostat demonstrated a favorable safety and tolerability profile, with serious adverse events (AEs) occurring in 2 participants (3%) during treatment with lorundrostat. Discontinuations because of treatment-emergent AEs were observed in 2 participants (3%) during the lorundrostat treatment period and 1 participant (2%) during the placebo treatment period.1
“These results are important because they show that lorundrostat, when added to standard-of-care therapy, reduced both blood pressure and proteinuria in patients with hypertension and chronic kidney disease,” said Matthew R. Weir, MD, director of the Division of Nephrology at the University of Maryland Medical Center, professor of medicine at the University of Maryland School of Medicine, and a scientific consultant to Mineralys Therapeutics. “The parallel reductions in systolic blood pressure and albuminuria underscore the potential of lorundrostat to improve cardio-renal outcomes in this high-risk population.”1
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