Lorundrostat Shows Positive Efficacy for Treatment of Hypertension

A multicenter, double-blind, randomized placebo-controlled trial aimed to assess the safety and efficacy of lorundrostat, an aldosterone synthase inhibitor, for the treatment of hypertension.

Results were published in The New England Journal of Medicine.

Participants taking two to five antihypertensive medications with office blood pressure readings greater than or equal to 140/90 mm Hg were transitioned to a standardized antihypertensive regimen for 3 weeks.

Those with an average 24-hour ambulatory blood pressure greater than or equal to 130/80 mm Hg after this period were then randomly assigned to receive either placebo, lorundrostat at a fixed dose of 50 mg daily (stable-dose group), or lorundrostat starting at 50 mg daily with an increase to 100 mg daily at week 4 if systolic blood pressure remained greater than or equal to 130 mm Hg (dose-adjustment group).

The primary endpoint was the change in 24-hour average systolic blood pressure from baseline to week 12, evaluated as the least-squares mean difference from placebo for each lorundrostat group. A key secondary endpoint was the placebo-adjusted change in 24-hour average systolic blood pressure from baseline to week 4, assessed across the combined lorundrostat groups.

A total of 285 participants (average age, 60 years) were randomly assigned to treatment: 94 to the stable-dose group, 96 to the dose-adjustment group, and 95 to the placebo group.

At week 12, the least-squares mean reduction in 24-hour average systolic blood pressure was -15.4 mm Hg in the stable-dose group, -13.9 mm Hg in the dose-adjustment group, and -7.4 mm Hg in the placebo group.

The placebo-adjusted reductions were -7.9 mm Hg (97.5% CI, -13.3 to -2.6) for the stable-dose group and -6.5 mm Hg (97.5% CI, -11.8 to -1.2) for the dose-adjustment group. At week 4, the placebo-adjusted reduction in 24-hour systolic blood pressure for the combined lorundrostat groups was -5.3 mm Hg (95% CI, -8.4 to -2.3).

Potassium levels exceeding 6.0 mmol/L were observed in five participants (5%) in the stable-dose group, seven participants (7%) in the dose-adjustment group, and none in the placebo group.

“Lorundrostat was associated with greater reductions in 24-hour average blood pressure than placebo in participants with uncontrolled and treatment-resistant hypertension,” the researchers concluded.

Reference

Laffin LJ, et al. NEJM. Published online April 23, 2025. doi:10.1056/NEJMoa2501440