ADVANCE-HTN Shows Benefit of Lorundrostat in Resistant Hypertension

The addition of lorundrostat, an investigational drug, to the treatment regimen of people with well-treated but uncontrolled and resistant hypertension could be beneficial, new data show.

“Lorundrostat effectively lowered blood pressure with an acceptable side effect profile,” said Luke Laffin, MD, a cardiologist at the Cleveland Clinic, Ohio, who presented the results of the ADVANCE-HTN study today at the American College of Cardiology (ACC) Scientific Session 2025 in Chicago.

ADVANCE-HTN is a pivotal phase 2b study designed to evaluate the efficacy and safety of lorundrostat as add-on therapy to standardized background treatment with two or three antihypertensive medications for patients with uncontrolled or resistant hypertension. 

In total, 285 patients were enrolled in the United States who had uncontrolled blood pressure despite taking two to five different medications. Participants were switched from their existing medications to a standard regimen of indapamide, olmesartan, and amlodipine, and then given lorundrostat 50 mg daily, lorundrostat 50 mg escalating up to 100 mg daily, or placebo.

Uncontrolled Blood Pressure

After 12 weeks, those in the lorundrostat 50-mg group had a placebo-adjusted reduction in 24-hour average ambulatory blood pressure of 7.9 mm Hg, whereas those in the dose-escalation group had a placebo-adjusted reduction of 6.5 mm Hg.

Overall, the drug was well-tolerated, Laffin reported, and side effects were consistent with other drugs that have a similar mechanism of action. Some participants experienced an increase in potassium in the blood, and some experienced a decrease in estimated glomerular filtration rate. Those in the dose-escalation group experienced more adverse effects than those in the 50-mg group but did not see a greater reduction in their blood pressure.

Lorundrostat is an aldosterone synthase inhibitor that reduces aldosterone levels by inhibiting CYP11B2, the enzyme responsible for its production. A previous phase 3 study, Launch-HTN, showed patients who received 50 mg of lorundrostat daily in addition to their existing medications had a placebo-adjusted reduction in office-measured blood pressure of 9.1 mm Hg after 6 weeks.

ADVANCE-HTN is an “important and exciting” study, said Gina Lundberg, MD, a cardiologist from Emory University in Atlanta, Georgia. Because it assessed 24-hour ambulatory blood pressure, it provides good real-world data, she explained.

The diversity of the study population — 40% of participants were women and 53% were Black — was also a benefit. “The study addressed the diverse population that we see in our clinics every day,” she said.

And although side effects will require continued monitoring, “it’s great to have one more thing in our toolkit to treat resistant patients for hypertension,” she said.

Laffin is a consultant for Mineralys Therapeutics, the makers of lorundrostat.