Kidney Week

Abstract: FR-OR091

Lorundrostat, a Novel Aldosterone Synthase Inhibitor (ASI), in Participants with Uncontrolled Hypertension, CKD, and Albuminuria: Results from Explore-CKD

Session Information

• Late-Breaking Research Orals - 2
  November 07, 2025 | Location: Grand Ballroom C, Convention Center
  Abstract Time: 05:06 PM - 05:18 PM

Category: Hypertension and CVD

• 1602 Hypertension and CVD: Clinical

Authors

• Weir, Matthew R., University of Maryland School of Medicine, Baltimore, Maryland, United States

Matthew R. Weir, MD

• Bhaduri, Sarbani, Mineralys Therapeutics Inc, Radnor, Pennsylvania, United States

Sarbani Bhaduri, MD, MS

• Lee, Keung, Triad Internal Medicine, Asheboro, North Carolina, United States

Keung Lee, MD

• Galvez, Oscar G., Qwayresearch LLC, Hialeah, Florida, United States

Oscar G. Galvez, MD

• Kooienga, Laura, Colorado Kidney Care Aurora Office, Aurora, Colorado, United States

Laura Kooienga, MD

• Kopjar, Branko, University of Washington, Seattle, Washington, United States

Branko Kopjar

• Novin, Matthew, Mineralys Therapeutics Inc, Radnor, Pennsylvania, United States

Matthew Novin, DO

• Rodman, David M., Mineralys Therapeutics Inc, Radnor, Pennsylvania, United States

David M. Rodman, MD

Background

Dysregulated aldosterone plays an important role in the pathogenesis of both hypertension (HTN) and CKD. Lorundrostat, a selective ASI, inhibits CYP11B2 (aldosterone synthase). In pivotal trials, lorundrostat showed clinically meaningful effects and was safe in treating uncontrolled HTN (uHTN) and treatment-resistant HTN. This is the first phase 2 trial of lorundrostat in participants with uHTN, CKD, and albuminuria.

Methods

The Explore-CKD trial (NCT06150924), a randomized, double-blind, placebo-controlled, crossover study, enrolled adults with uHTN and CKD, baseline estimated GFR (eGFR) ≥30 mL/min/1.73m², urinary albumin-creatinine ratio (UACR) 200–5000 mg/g and on stable doses of SGLT2i and ACEi/ARB. Participants were randomized to lorundrostat 25 mg/day-placebo (LP) or placebo-lorundrostat 25 mg/day (PL) in 4-week treatment sequences with a 4-week washout in between. The primary endpoint was the change from baseline in automated office systolic blood pressure (AOSBP). Other endpoints included the placebo-adjusted change from baseline in spot UACR and cystatin-C eGFR.

Results

Of 59 participants, 30 were randomized to LP and 29 to PL. Mean age was 64.6 years, mean body mass index was 33 kg/m², 69.5% were male, and 76.3% had diabetes. Mean±SD baseline values were AOSBP 149±10.4 mmHg and eGFR 43±15.0 mL/min/1.73m². Geometric mean baseline spot UACR was 516±2.5 mg/g. Least square mean reduction in AOSBP was 9.3 mmHg (90% CI, -12.5 to -6.1, p<0.0001) for lorundrostat and 1.8 mmHg (90% CI, -5.0 to 1.5, ns) for placebo (placebo-adjusted reduction of 7.5 mmHg, 90% CI, -11.6 to -3.4, p=0.0024). Placebo-adjusted reduction in geometric mean of spot UACR was 25.6% (90% CI, -35.8 to -13.7, p=0.0015). Placebo-adjusted change in eGFR was -4.6% (90% CI, -8.1 to -1.0, p=0.036). Three participants discontinued treatment due to 4 adverse events: hyperkalemia, acute kidney injury, retinal detachment, and CKD.

Conclusion

Lorundrostat was effective in reducing AOSBP and albuminuria in CKD participants with concurrent uHTN receiving SGLT2i. This parallel reduction is anticipated to provide meaningful benefits in improving CKD-associated cardio-renal outcomes.

Funding

• Commercial Support – Mineralys Therapeutics Inc.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.202544j6mmcr