Lorundrostat Improves Blood Pressure in Uncontrolled Hypertension

Use of lorundrostat was effective in lowering blood pressure among patients with uncontrolled hypertension, according to new data presented at the American College of Cardiology (ACC) 2025 Annual Scientific Sessions.

Named the ADVANCE-HTN trial, results of the study suggest use of lorundrostat, an aldosterone synthase inhibitor from Mineralys Therapeutics, was associated with statistically significant placebo-adjusted reductions in systolic blood pressure (SBP) at 12 weeks, with lorundrostat patients 3 times more likely to achieve an SBP less than 125 mmHg at week 4 compared to their placebo counterparts.

“Lorundrostat effectively lowered blood pressure with an acceptable side effect profile,” said principal investigator Luke Laffin, MD, a cardiologist at Cleveland Clinic.2 “More studies are needed; however, this drug could be another tool in our armamentarium to reduce blood pressure and, ultimately, reduce the risk from uncontrolled hypertension in terms of outcomes like strokes, heart attacks and heart failure.”

Launched in 2023, ADVANCE-HTN was designed as randomized, double-blind, placebo- controlled, parallel-arm, multicenter trial to examine use of lorundrostat among participants with elevated blood pressure despite taking 2 to 5 blood pressure-lowering medications before joining the study. Conducted at 103 sites in the US, the trial enrolled 285 patients who were randomized in a 1:1:1 ratio to placebo, lorundrostat 50 mg, or lorundrostat 50 to 100 mg. The overall study population had a mean age of 60 years, 40% were women, and 53% were Black.1

Results of the study demonstrated lorundrostat was associated with a statistically significant effect on 24-hour average SBP at week 12, with a least squares mean (LSM) change in SBP of -7.4 mmHg with placebo group, -15.4 mmHg for the lorundrostat 50 mg group, and -13.9 mmHg for the lorundrostat 50 to 100 mg group. The placebo-adjusted change in SBP for the lorundrostat 50 mg group was -7.9 mmHg (95% CI, -13.3 to -2.6; P = .001), while the placebo-adjusted change for the lorundrostat 50 to 100 mg group was -6.5 mm Hg (95% CI, -11.8 to -1.2; P = .006).1

When examining secondary endpoints, results indicated treatment with lorundrostat 50 mg resulted in a greater reduction in 24-hour average SBP compared with placebo at week 4, with a LSM change in 24-hour SBP of -6.2 mmHg with placebo and -11.5 mmHg with lorundrostat, which correlates to a placebo-adjusted reduction of -5.3 mm Hg (95% CI, -8.4 to -2.3; P <.001). Additionally, a greater proportion of patients receiving lorundrostat achieved a 24-hour average SBP of less than 125 mmHg at week 4 compared with placebo (41% vs 18%; Odds Ratio, 3.3; 95% CI, 1.4 to 7.8; P <.001).1

Subgroup analysis based on background antihypertensive therapy demonstrated a differential effect of lorundrostat. Among patients receiving two background medications, lorundrostat treatment led to a LSM change in SBP of -11.2 mm Hg compared with -5.1 mm Hg for placebo, yielding a placebo-adjusted reduction of -6.1 mm Hg (95% CI, -10.8 to -1.4; P = 0.001). In contrast, among those on three background medications, the LSM change in SBP was –11.8 mm Hg with lorundrostat versus -7.2 mm Hg with placebo, resulting in a placebo-adjusted reduction of -4.6 mm Hg (95% CI, -10.6 to 1.5; P = .060).1

Safety data from the trial suggested serious adverse events occurred in 2% of the placebo group, 6% of the lorundrostat 50 mg group, and 8t% of the lorundrostat 50 to 100 mg group. Hyponatremia occurred in 6%, 9%, and 11% percent of each group, respectively, while hyperkalemia above 6.0 mmol per liter occurred in 0%, 5%, and 7%. Investigators noted confirmed hyperkalemia was reported in 0%, 2%, and 3% percent of patients receiving placebo, lorundrostat 50 mg, and lorundrostat 50 to 100 mg, respectively.1

“With the recent announcement of data from our two pivotal trials, we now have a comprehensive dataset demonstrating the robust and consistent blood pressure reductions of lorundrostat in two distinct but complementary patient populations—real-world setting in Launch-HTN, and those with optimally treated yet uncontrolled hypertension in the specialist setting in Advance-HTN,” stated Jon Congleton, Chief Executive Officer of Mineralys Therapeutics.3

References:

1. Laffin L. Efficacy Of Lorundrostat, A Novel Aldosterone Synthase Inhibitor, In Patients With Uncontrolled Hypertension On A Standardized Antihypertensive Medication Regimen. Presented at: American College of Cardiology (ACC.25) Annual Scientific Session. March 29 – 31, 2025. Chicago, Il.

2. American College of Cardiology. Lorundrostat Lowers Blood Pressure Compared with Placebo at 12 Weeks - American College of Cardiology. American College of Cardiology. Published March 29, 2025. Accessed March 30, 2025. https://www.acc.org/About-ACC/Press-Releases/2025/03/29/17/24/Lorundrostat-Lowers-Blood-Pressure-Compared.

3. Mineralys Therapeutics. Mineralys Therapeutics, Inc. Mineralys Therapeutics, Inc. Published March 29, 2025. Accessed March 30, 2025. https://ir.mineralystx.com/news-events/press-releases/detail/66/mineralys-therapeutics-announces-late-breaking-data-from.