Lorundrostat Significantly Lowers Blood Pressure in Key Hypertension Trials

Lorundrostat showed promising efficacy and safety in the pivotal phase 3 Launch-HTN (NCT06153693) and phase 2 Advance-HTN (NCT06153693) trials, which evaluated the oral aldosterone synthase inhibitor for uncontrolled hypertension (uHTN) or resistant hypertension (rHTN).¹

Announced by Mineralys Therapeutics, Inc, both trials showed that lorundrostat achieved statistically significant and clinically meaningful reductions in systolic blood pressure while maintaining a favorable safety and tolerability profile.

Jon Congleton | Image Credit: © Mineralys Therapeutics

“The positive results and clinically meaningful reduction in blood pressure observed in the Launch-HTN and Advance-HTN trials show us that lorundrostat has the potential to be a transformative new therapy for the approximately 15 to 20 million patients with uncontrolled hypertension in the United States,” said Jon Congleton, CEO of Mineralys, in a statement.¹

Launch-HTN

The global, randomized, double-blind, placebo-controlled Launch-HTN trial enrolled eligible adults who could not meet blood pressure goals despite treatment with 2 to 5 antihypertensive medications. Launch-HTN utilized automated office blood pressure (AOBP) measurements and allowed participants to remain on existing medications to represent a real-world setting.²

At 6 weeks, the trial met its primary end point, with lorundrostat 50 mg achieving a statistically significant 16.9 mm Hg reduction in systolic blood pressure and a 9.1 mm Hg placebo-adjusted reduction (P < .0001), as determined by AOBP measurements. At the 12-week end-of-treatment mark, lorundrostat 50 mg sustained a 19.0 mm Hg reduction in systolic blood pressure and a 11.7 mm Hg placebo-adjusted reduction (P < .0001).

Twelve participants (2.2%) who received 50 mg and 2 participants (0.7%) who also received 50 mg but with optional dose escalation to 100 mg experienced treatment-emergent serious adverse events (SAEs) compared with 8 (3.0%) in the placebo arm. A single participant (0.1%) reported treatment-related SAEs in the 50-mg arm. Hyperkalemia (serum potassium ≥ 6.0 mmol/L) was present in 1.1% and 1.5% of patients in the 50-mg and 50-100-mg arms, respectively.

Manish Saxena, MBBS | Image Credit: © LinkedIn

“Uncontrolled and resistant hypertension remains a global health concern as it continues to be the leading cause of cardiovascular deaths, heart attacks, and strokes,” said Manish Saxena, MBBS, a hypertension specialist from Barts Health NHS Trust, in a statement.¹ “Given today’s announcement, lorundrostat could be a good treatment option for millions of patients with high blood pressure."

Advance-HTN

The randomized, double-blind, placebo-controlled Advance-HTN trial assessed the efficacy and safety of lorundrostat as an add-on therapy for adults on an optimized background treatment of 2 to 3 antihypertensive medications. The trial met its primary end point, with placebo-adjusted reductions of 7.9 mm Hg in 24-hour average systolic blood pressure at 12 weeks with lorundrostat 50 mg.

Other outcome measures, including efficacy data in the dose-escalation cohort, safety, and tolerability, remained consistent with the Launch-HTN trial. Hyperkalemia was present in 5.3% and 7.4% of patients in the 50-mg and 50-100-mg arms, respectively.

Based on these efficacy and safety findings, Mineralys concluded that lorundrostat has a favorable benefit-risk profile. The company plans to present full Advance-HTN results at the 2025 American College of Cardiology Scientific Sessions in Chicago. Additionally, the ongoing Transform-HTN open-label extension trial will provide further safety and efficacy data on lorundrostat for hypertension.

“We have now completed 3 successful clinical trials demonstrating the efficacy, safety, and tolerability of lorundrostat and the importance of targeting dysregulated aldosterone,” Congleton added. “We believe the clinical profile observed for lorundrostat supports the potential regulatory approval of this novel agent and its significant commercial value.”

References

1. Mineralys Therapeutics announces positive topline results from launch-HTN and advance-HTN pivotal trials of LORUNDROSTAT for the treatment of uncontrolled or resistant hypertension. News release. Mineralys Therapeutics, Inc; March 10, 2025. Accessed March 10, 2025. https://ir.mineralystx.com/news-events/press-releases/detail/60/mineralys-therapeutics-announces-positive-topline-results
2. Lorundrostat. Mineralys Therapeutics. Accessed March 10, 2025. https://mineralystx.com/science/#lorundrostat