Lorundrostat lowers BP in adults with hypertension, CKD: Topline data

Key takeaways:

• Topline data show lorundrostat lowers systolic blood pressure in patients with hypertension and chronic kidney disease.
• The drug also showed expected reductions in urine albumin-to-creatinine ratio and eGFR.

Mineralys Therapeutics announced positive topline results from its phase 2 Explore-CKD trial, in which lorundrostat lowered blood pressure in patients with hypertension and chronic kidney disease.

The company reported the trial met the primary endpoint, showing significant reduction in systolic automated office BP and urine albumin-to-creatinine ratio with favorable safety and tolerability.

Explore-CKD was a phase 2, randomized, double-blind, placebo-controlled, crossover trial to evaluate the efficacy and safety of 4 weeks of once daily lorundrostat 25 mg on top of background treatment including SGLT2 inhibition and ACE inhibition or angiotensin receptor blockade in patients with hypertension and CKD with an estimated glomerular filtration rate of 30 mL/min/1.73m² or more and albuminuria.

The primary endpoint of placebo-adjusted change in systolic BP was significantly lower among participants assigned to lorundrostat, an investigational aldosterone synthase inhibitor, vs. placebo (–7.5 mm Hg; P = .0024), according to a company press release.

Placebo-adjusted changes in spot urine albumin-to-creatinine ratio (–25.6% mg/g; P = .0015) and eGFR (–4.58%; P = .0362) were also favorable in the lorundrostat arms.

Two treatment-emergent adverse events leading to discontinuation were reported in the lorundrostat arm. One patient discontinued treatment due to elevation of potassium associated with reduced eGFR and the other patient discontinued due to reduction in eGFR, according to the release.

“Prolonged elevations in blood pressure in patients with compromised renal function can damage the small blood vessels in the kidneys, further reducing their ability to function properly,” Matthew R. Weir, MD, director of the division of nephrology at the University of Maryland Medical Center and professor of medicine at the University of Maryland School of Medicine, said in the release. “The evidence generated from this trial demonstrates the unique mechanism of action and benefit of lorundrostat in lowering systolic blood pressure and [urine albumin-to-creatinine ratio]. Lorundrostat shows significant potential in the management of hypertension and related kidney disease.”

As Healio previously reported, in the phase 2 ADVANCE-HTN trial, lorundrostat lowered 24-hour BP in a cohort of adults with well-treated, uncontrolled, treatment-resistant hypertension, while in the phase 2TARGET-HTN trial, lorundrostat was associated with significant reductions in automated office BP in patients with uncontrolled hypertension, with a particularly strong effect in people with obesity.

The pivotal phase 3 LAUNCH-HTN trial, which enrolled adults with resistant hypertension and uses office BP data, has been completed, but the data have not yet been peer reviewed and presented, according to Luke J. Laffin, MD, co-director of the Center for Blood Pressure Disorders at Cleveland Clinic, who previously discussed the results of ADVANCE-HTN at the American College of Cardiology Scientific Session in March.

In January, the FDA greenlighted the phase 2 EXPLORE-OSA trial evaluating lorundrostat in adults with obstructive sleep apnea and hypertension.