RADNOR, PA — Mineralys Therapeutics Inc. (Nasdaq: MLYS) reported that its experimental hypertension drug lorundrostat significantly reduced blood pressure and urinary protein levels in patients with chronic kidney disease, according to Phase 2 clinical trial results published in the medical journal Kidney International.
The findings from the 59-patient Explore-CKD trial provide additional evidence supporting the company’s effort to expand lorundrostat’s potential use beyond uncontrolled and resistant hypertension to patients with related kidney disease.
Patients receiving 25 milligrams of lorundrostat once daily experienced an average 9.3 mmHg reduction in systolic blood pressure after four weeks, compared with a 1.8 mmHg reduction during placebo treatment.
The placebo-adjusted difference of 7.5 mmHg was statistically significant, meeting the trial’s primary endpoint.
The study also found reductions in albuminuria, a measure of albumin leaking into urine that can indicate kidney damage.
Urinary albumin-to-creatinine ratio declined 30.5% from baseline during lorundrostat treatment, representing a statistically significant placebo-adjusted reduction of 25.6%.
Additional testing showed placebo-adjusted reductions of 26.1% in 24-hour urinary albumin-to-creatinine ratio and 22.1% in 24-hour urinary protein-to-creatinine ratio.
Serum aldosterone, a hormone involved in regulating blood pressure and fluid balance, decreased 41.5% during lorundrostat treatment, compared with a 1.8% increase during placebo treatment.
Plasma renin activity increased 75.2% with lorundrostat, while no clinically meaningful changes in serum cortisol were observed.
Lorundrostat works by inhibiting aldosterone synthase, an enzyme responsible for producing aldosterone. Excess aldosterone can contribute to sodium retention, elevated blood pressure and kidney injury.
The Explore-CKD trial enrolled 59 participants at 42 U.S. sites. Patients had uncontrolled hypertension, stage 1 through 3b chronic kidney disease and albuminuria despite receiving background treatment that included an ACE inhibitor or angiotensin receptor blocker and an SGLT2 inhibitor.
The randomized, double-blind, placebo-controlled crossover study evaluated each treatment over four weeks, with blood pressure reduction serving as its primary efficacy measure.
Participants had an average age of 64.6 years, and 76% had type 2 diabetes. Nearly two-thirds were taking at least three antihypertensive medications.
Baseline systolic blood pressure averaged 149 mmHg, while estimated kidney filtration function averaged 43 mL/min/1.73 m².
The company reported that adverse events were consistent with those observed in earlier lorundrostat trials and with the drug’s mechanism of action.
Matthew R. Weir, director of nephrology at the University of Maryland Medical Center and lead author of the publication, said the results suggest the drug could address blood pressure that remains uncontrolled despite existing treatment.
“The Explore-CKD results demonstrate that lorundrostat may help CKD patients reduce otherwise uncontrolled high blood pressure and potentially improve their kidney function,” said Weir, who also serves as a scientific consultant to Mineralys.
The trial’s short treatment periods and limited enrollment mean the findings do not establish whether lorundrostat can prevent long-term kidney function decline or reduce the need for dialysis.
Mineralys plans to evaluate longer-term findings from Explore-CKD participants enrolled in the Transform-HTN open-label extension study.
The company has also completed its Phase 3 Launch-HTN and Phase 2 Advance-HTN trials, which evaluated lorundrostat for uncontrolled or resistant hypertension.
Chronic kidney disease affects an estimated 37 million U.S. adults, according to figures cited from the Centers for Disease Control and Prevention. Hypertension can contribute to declining kidney function, while worsening kidney disease can make blood pressure more difficult to control.
Lorundrostat remains investigational. Mineralys is developing the oral drug for uncontrolled and resistant hypertension and related conditions, including chronic kidney disease and obstructive sleep apnea.
Support the local news that supports Chester County. MyChesCo delivers reliable, fact-based reporting and essential community resources—free for everyone. If you value that, click here to become a patron today.