Clinical Trial Shows Novel Drug Safely and Significantly Treats Uncontrolled Hypertension

CLEVELAND: Findings from a clinical trial led by a Cleveland Clinic cardiologist showed that lorundrostat – a new type of blood pressure medication — significantly decreased blood pressure in patients with uncontrolled hypertension.

Findings were presented today during a late breaking science session at the American College of Cardiology’s annual meeting in Chicago.

High blood pressure, also called hypertension, occurs when the force of blood pushing against the artery walls is consistently too high. This damages the arteries over time and can lead to serious complications like heart attack or stroke.

Uncontrolled or resistant hypertension is when blood pressure remains high or unmanaged, despite taking medications. People with hard-to-treat, resistant hypertension have an even higher risk of stroke, kidney disease and heart failure than those whose high blood pressure is regulated.

Lorundrostat was developed to address abnormally elevated aldosterone, a hormone the adrenal glands release that regulates blood pressure by managing the levels of sodium and potassium in the blood. Aldosterone synthase inhibitors are a novel class of blood pressure-lowering medications that decrease the body’s production of aldosterone. Medicines currently available for patients block the receptor for aldosterone, but aldosterone can still be circulating and have a negative impact on patients. Up to 25% of all people with hypertension exhibit abnormal aldosterone levels.

In the Advance-HTN Phase 2b randomized clinical trial, 285 participants with uncontrolled hypertension at 103 sites in the United States were given a placebo or one of two different doses of lorundrostat, 50mg or 50-100mg a day. The drug’s efficacy was assessed using 24-hour ambulatory blood pressure monitor rather than using blood pressures measured in an office setting. The monitor is a wearable cuff that measures blood pressure every 15-to-30 minutes during the day and every 30-to-60 minutes overnight. Those patients taking the 50mg daily dose of lorundrostat saw a decrease of 15.4 blood pressure points when compared to placebo, while the 50-100mg group saw an average drop of 13.9 points. The placebo group dipped by 7.4 points.

“Twenty-four-hour ambulatory blood pressure monitoring is the gold standard for blood pressure measurement and it is important to understand a drug’s effects not only on office blood pressure, but outside the office, including when sleeping,” said the study’s lead author Luke Laffin, M.D., co-director of the Center for Blood Pressure Disorders in the Heart, Vascular & Thoracic Institute at Cleveland Clinic. “As clinicians look for new, safe and effective medications to help the millions of patients with uncontrolled hypertension, these results are encouraging.”

Of the participants, 53% were Black. The rate of high blood pressure among Black Americans is the highest in the world, with about 55% suffering from hypertension.

“Testing new drugs in the patient populations that really need them is paramount,” said Dr. Laffin. “Black Americans carry an outsized risk for complications from uncontrolled hypertension compared with any other ethnicity.”

In 2023, the Target HTN Phase 2 Trial, a dose-finding trial of lorundrostat, suggested safe and effective blood pressure control. A Phase 3 trial is underway that enrolled eligible adult participants who failed to achieve their blood pressure goals despite being on two-to-five medications.

The study was funded by Mineralys Therapeutics, developer of lorundrostat.

Dr. Laffin has served on steering committees for Mineralys Therapeutics, however, he did not receive any compensation.