Lorundrostat Phase II Results

In the trial, lorundrostat 50 mg demonstrated a 15.4 mmHg absolute reduction and a 7.9 mmHg placebo-adjusted reduction at week 12. Additionally, lorundrostat demonstrated a favorable safety and tolerability profile, with modest changes in potassium, sodium and eGFR, and a low discontinuation rate.

“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. “These findings underscore lorundrostat’s clinical utility across diverse care settings and also provide critical insights for both primary care providers, who manage the vast majority of hypertension patients, and specialists, who treat the most complex cases. We are excited about the potential impact lorundrostat could have as a novel treatment to address a significant unmet need in hypertension care.”

“Twenty-four-hour ambulatory blood pressure monitoring is the gold standard for assessing the true impact of an antihypertensive therapy, as it provides a more comprehensive picture of blood pressure control beyond the office setting, including overnight readings,” stated Luke Laffin, M.D., co-director of the Center for Blood Pressure Disorders in the Heart, Vascular & Thoracic Institute at Cleveland Clinic and the study’s lead author. “Along with rigorous evaluations in the Advance-HTN trial, the double-digit drop in blood pressure readings observed with lorundrostat in this trial are particularly notable given the complex characteristics of the patient population, which included a high proportion of individuals who have been historically underrepresented in hypertension clinical trials and who face a disproportionate burden of treatment-resistant hypertension.”

Following the recently announced positive topline data from both Advance-HTN and Launch-HTN pivotal trials, detailed results from Advance-HTN were presented in a late-breaking session at the American College of Cardiology’s Annual Scientific Session & Expo (ACC.25) on Saturday, March 29, 2025, at 1:30 p.m. CT.

Efficacy Results; The Advance-HTN trial was a randomized, double-blind, placebo-controlled Phase II pivotal trial that evaluated the efficacy and safety of lorundrostat for the treatment of confirmed uncontrolled or resistant hypertension, when used as add-on therapy to an optimized background treatment of two or three antihypertensive medications in adult subjects. The trial was designed to evaluate lorundrostat in an uncontrolled or resistant hypertensive population at the highest risk and which would normally be treated by a specialist given severity of their condition.

Principal Findings: The primary outcome was change in 24-hour average SBP from baseline (randomization) to week 12. Results showed:

• i.Placebo: -7.4 points (mm Hg)
• ii.Lorundrostat 50 mg: -15.4 points. Placebo adjusted: -7.9 points (-13.3 to -2.6) p=0.001
• iii.Lorundrostat 50-100 mg: -13.9 points. Placebo adjusted: -6.5 points ( -11.8 to -1.2) p=0.006

Secondary outcomes include:

• i. Change in 24-hour average SBP from baseline to week 4: Placebo: -6.2 points vs. lorundrostat 50 mg: -11.5% points. Placebo adjusted: -5.3 points (-8.4 to -2.3 points)
• ii. Change in office SBP from baseline to week 12 among participants escalated to 100 mg daily (n=19): - 17.5 mm Hg (-30.3 to -4.7 mm Hg) p<0.001
• iii. Proportion of participants with 24-hour average SBP <125 mm Hg at week 4 in placebo (18%) vs. lorundrostat 50 mg (41%): odds ratio (OR), 3.3 (1.4-7.8) p<0.001
• iv. Change in 24-hour average SBP from baseline to week 4 by number of BP medications in standardized regimen (i.e., in patients taking two BP medications), placebo was -5.1 (n=60) vs. lorundrostat (n=117) -11.2, placebo adjusted -6.1 (-10.8 to -1.4) p=0.001. In patients taking three BP medications, placebo adjusted (n=34): - 7.2 points vs. lorundrostat (n=71): - 11.8 points, placebo adjusted result: -4.6 points (-10.6 to 1.5) p=0.06
• v.Importantly, in the adverse events, hyperkalemia was notably different in the placebo group (0%), vs. lorundrostat 50 mg (5%) vs. lorundrostat 50-100 mg (7%)

Interpretation: In patients with uncontrolled hypertension and treatment-resistant hypertension in the Advance-HTN trial, the use of lorundrostat 50 mg and 50-100 mg lowered 24-hour BP at week 12, with higher rates of adverse events at the higher dose. The trial recruited a diverse population with 40% women and >50% African Americans; the BP effect was achieved irrespective of race, gender, or weight. Higher levels of hyperkalemia and hyponatremia were seen in the lorundrostat group.. The use of a therapy which targets aldosterone production is promising as a new treatment in resistant hypertension if these data are confirmed by subsequent phase III clinical trials.