Novel Drug Lorundrostat Shows Significant Promise for Uncontrolled Hypertension in Phase 2b Trial
Key Insights
Cleveland Clinic-led clinical trial demonstrates lorundrostat, an aldosterone synthase inhibitor, reduced systolic blood pressure by 8 points more than placebo in patients with uncontrolled hypertension (search).
The 12-week Advance-HTN trial included 285 participants with 53% being Black Americans, a population that carries disproportionately high risk for hypertension (search) complications.
Lorundrostat represents a new class of blood pressure medications that directly reduces aldosterone production, potentially offering treatment options for the 30-40% of patients whose hypertension (search) remains uncontrolled with current therapies.
A novel blood pressure medication has demonstrated significant efficacy in treating patients with uncontrolled hypertension (search), according to findings presented at the American College of Cardiology's annual meeting in Chicago. The experimental drug lorundrostat reduced systolic blood pressure by an average of 8 points more than placebo when added to standard hypertension therapies.
The Phase 2b Advance-HTN randomized clinical trial, led by Cleveland Clinic cardiologist Dr. Luke Laffin, enrolled 285 participants across 103 U.S. sites. All participants had hypertension (search) that remained uncontrolled despite taking multiple medications.
"As clinicians look for new, safe and effective medications to help the millions of patients with uncontrolled hypertension (search), these results are encouraging," said Dr. Laffin, co-director of the Center for Blood Pressure Disorders in the Heart, Vascular & Thoracic Institute at Cleveland Clinic.
A Novel Mechanism for Blood Pressure Control
Lorundrostat belongs to a new class of medications called aldosterone synthase inhibitors. Unlike existing treatments that block aldosterone receptors, lorundrostat works by directly reducing the body's production of aldosterone, a hormone released by the adrenal glands that regulates blood pressure by managing sodium and potassium levels.
"This new potential therapy for hypertension (search) is exciting," Dr. Laffin noted. "We do a poor job controlling blood pressure in the U.S."
According to the Centers for Disease Control and Prevention, nearly half of U.S. adults have hypertension (search), with less than 25% having their blood pressure adequately controlled. Uncontrolled hypertension significantly increases the risk of serious complications including heart attack (search), stroke (search), kidney disease (search), and heart failure (search).
Trial Design and Results
The 12-week trial standardized participants' existing blood pressure medications, then randomly assigned them to receive either a placebo or one of two doses of lorundrostat (50mg or 50-100mg daily). Efficacy was assessed using 24-hour ambulatory blood pressure monitoring at baseline, four weeks, and twelve weeks.
"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," Dr. Laffin explained.
Participants taking the 50mg daily dose of lorundrostat experienced a decrease of 15.4 blood pressure points compared to 7.4 points in the placebo group, resulting in a net drug effect of 8 points. The higher dose (50-100mg) did not demonstrate additional benefit, with an average drop of 13.9 points.
Dr. Deepak Bhatt, director of the Mount Sinai Fuster Heart Hospital in New York City, who was not involved in the study, commented on the clinical significance: "With a decrease of 8 points, say from 170 to 162, that is the range where you would in a longer-term study see reductions in heart attacks and strokes."
Focus on High-Risk Populations
Notably, 53% of trial participants were Black Americans, a population with disproportionately high hypertension (search) rates. According to the American Heart Association, approximately 55% of Black adults have high blood pressure.
"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 (search) compared with any other ethnicity."
Dr. Oscar Cingolani, director of the hypertension (search) program at Johns Hopkins Medicine, who was not involved in the research, called the inclusion of many Black patients "a big, big thing," noting that "African Americans tend to be more responsive to this pathway."
Safety Profile and Next Steps
The most significant safety concern observed was elevated potassium levels in some patients receiving lorundrostat, which would require monitoring as high potassium can lead to abnormal heart rhythms.
The drug has already completed Phase 3 trials, though those results have not yet been published. According to Dr. Laffin, lorundrostat could potentially be available within 12 to 18 months, pending FDA review.
The study was funded by Mineralys Therapeutics, the developer of lorundrostat. The results will be published in The New England Journal of Medicine.
For the estimated 30-40% of hypertension (search) patients who don't achieve adequate control with current medications, lorundrostat represents a promising new treatment option targeting a different biological pathway than existing therapies.