RADNOR, Pennsylvania, United States — October 28, 2026
Mineralys Therapeutics, Inc., a biopharmaceutical company developing treatments for hypertension and aldosterone-related conditions, announced publication of the full Phase 2 Explore-CKD trial results in Kidney International. The study evaluated lorundrostat, an investigational aldosterone synthase inhibitor, in 59 participants with uncontrolled hypertension, stage 1 to 3b chronic kidney disease (CKD) and albuminuria. When added to background treatment that included an SGLT2 inhibitor and an ACE inhibitor or angiotensin receptor blocker, lorundrostat 25 mg once daily achieved a statistically significant placebo-adjusted reduction of 7.5 mmHg in systolic blood pressure after four weeks. The study also reported reductions in urinary albumin and protein levels, alongside a 41.5% decrease in serum aldosterone. These findings add to the clinical evidence supporting further investigation of aldosterone inhibition for patients with difficult-to-control hypertension and kidney disease, although longer-term studies are needed to determine whether the observed changes translate into sustained kidney and cardiovascular benefits.
Explore-CKD Demonstrates Significant Blood Pressure Reduction
The randomized, double-blind, placebo-controlled crossover trial enrolled 59 participants across 42 sites in the United States. Participants had uncontrolled hypertension, CKD and albuminuria, with approximately 64% taking three or more antihypertensive medications at baseline. The primary endpoint assessed the change in automated office systolic blood pressure after four weeks of lorundrostat compared with placebo. Systolic blood pressure decreased by 9.3 mmHg during lorundrostat treatment, compared with 1.8 mmHg during placebo treatment, resulting in a placebo-adjusted reduction of 7.5 mmHg (95% confidence interval, −12.3 to −2.7; p=0.0024). Diastolic blood pressure decreased by 3.9 mmHg with lorundrostat and 1.4 mmHg with placebo. These results suggest that targeting aldosterone production may help lower blood pressure in patients whose hypertension remains uncontrolled despite existing treatment. However, the trial was relatively small and short, and additional research will be needed to establish the durability of the blood pressure effect and its impact on long-term clinical outcomes.
Urinary Protein and Hormonal Findings Support Further Kidney Research
In addition to lowering blood pressure, lorundrostat was associated with reductions in markers of kidney damage. Urinary albumin-to-creatinine ratio (UACR) decreased by 30.5% from baseline, with a placebo-adjusted reduction of 25.6% at week four (p=0.0015). Significant placebo-adjusted reductions were also reported in 24-hour UACR of 26.1% (p<0.0001) and 24-hour urine protein-to-creatinine ratio of 22.1% (p=0.0002). Serum aldosterone decreased by 41.5% during lorundrostat treatment, while plasma renin activity increased by 75.2%; corresponding changes with placebo were an increase of 1.8% in aldosterone and 4.2% in renin activity. No clinically meaningful changes in serum cortisol were observed in either treatment sequence. The nature and incidence of adverse events were reported to be similar to those seen in earlier lorundrostat trials and consistent with the drug’s mechanism of action. Although reduced albuminuria is an important finding, longer follow-up is required to determine whether these short-term changes reduce the risk of CKD progression or kidney failure.
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Lorundrostat Advances Mineralys’ Strategy for Aldosterone-Driven Conditions
Lorundrostat is an investigational oral medication designed to selectively inhibit CYP11B2, the enzyme responsible for producing aldosterone. Excess aldosterone can contribute to sodium retention, elevated blood pressure, inflammation and tissue fibrosis, potentially worsening both hypertension and kidney injury. Mineralys is developing lorundrostat for uncontrolled or resistant hypertension and related conditions, including CKD and obstructive sleep apnea. The company said longer-term follow-up data from Explore-CKD participants entering the Transform-HTN open-label extension study are expected to provide additional information. Lorundrostat is also being evaluated in other clinical programs, including the Phase 3 Launch-HTN trial and Phase 2 Advance-HTN trial. The Explore-CKD publication strengthens the evidence for continued study of aldosterone synthase inhibition in patients with overlapping hypertension and kidney disease. Nevertheless, lorundrostat remains investigational, and further studies are needed to determine its long-term safety, efficacy and potential role alongside established CKD and blood pressure treatments.
Source:Mineralys Therapeutics Press release
