Lorundrostat Significantly Lowers Blood Pressure in Key Hypertension Trials

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

Announced by Mineralys Therapeutics, Inc. on March 10, 2025, both trials showed that lorundrostat achieved statistically significant and clinically meaningful reductions in systolic blood pressure while maintaining a favorable safety and tolerability profile.

“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, chief executive officer of Mineralys Therapeutics.

Launch-HTN

The global, randomized, double-blinded, placebo-controlled Launch-HTN trial enrolled eligible adults who could not meet blood pressure goals despite treatment with 2–5 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 endpoint, with lorundrostat 50 mg achieving a statistically significant –16.9 mmHg reduction in systolic blood pressure and a –9.1 mmHg 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 mmHg reduction in systolic blood pressure and a –11.7 mmHg placebo-adjusted reduction (P <.0001).

Approximately 12 participants (2.2%) and 2 participants (0.7%) experienced treatment-emergent serious adverse events (SAEs) in the 50 mg and 50 mg with optional dose escalation to 100 mg arms, respectively, 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 50–100mg arms, respectively.

“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.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–-3 antihypertensive medications. The trial met its primary endpoint with placebo-adjusted reductions of –7.9 mmHg 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 (serum potassium ≥6.0 mmol/L) was present in 5.3% and 7.4% of patients in the 50 mg and 50–100mg 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 three 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. 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, an Investigational Drug, is a novel, oral, highly selective, once-daily aldosterone synthase inhibitor (ASI).1​. Mineralys Therapeutics. Accessed March 10, 2025. https://mineralystx.com/science/#lorundrostat.