Transform-HTN: Lorundrostat Maintains Blood Pressure Reductions in Open-Label Extension

Long-term lorundrostat treatment has resulted in sustained blood pressure control with an adequate safety profile among patients with uncontrolled hypertension, according to the open-label extension study Transform-HTN.¹

These data were presented at the American Heart Association (AHA) Scientific Sessions 2026 in Chicago, Illinois, by Luke Laffin, MD, a preventive cardiologist, co-director of the Center for Blood Pressure Disorders, and Medical Director of C5Research at Cleveland Clinic and an associate professor of medicine at the Cleveland Clinic Lerner College of Medicine.¹

“I think we now understand better that people who take lorundrostat maintain blood pressure reductions throughout this open-label extension period,” Laffin told HCPLive in an exclusive interview. “I think these data clearly make the case for aldosterone’s role in uncontrolled hypertension, because we also paired it with biomarkers that show aldosterone essentially staying lower throughout the treatment course with lorundrostat.”

Lorundrostat, an investigational aldosterone synthase inhibitor (ASI) in development by Mineralys Therapeutics, demonstrated its blood pressure-lowering capacity in the 12-week, randomized, double-blind, placebo-controlled Launch-HTN trial. Briefly, Launch-HTN enrolled patients with uncontrolled hypertension, including treatment-resistant hypertension, and randomly assigned them in a 1:2:1 ratio to 50 mg of lorundrostat daily for 6 weeks followed by 100 mg of lorundrostat for 6 weeks if certain criteria were met, or to 50 mg of lorundrostat or matching placebo daily for 12 weeks.²

A total of 1083 patients were enrolled in Launch-HTN, with a mean age of 61.6 years. The pooled 50 mg group, encompassing 808 patients, saw a least-squares mean change in automated office systolic blood pressure of -16.9 mmHg (95% CI, -19 to -14.9) at week 6 versus -7.9 mmHg (95% CI, -11.5 to -4.2) for placebo (least-squares mean difference, -9.1 mmHg [95% CI, -13.3 to -4.9]; P <.001). Treatment-emergent adverse events occurred in 49.9% of patients and were mostly mild or moderate.²

For Transform-HTN, Laffin and colleagues included patients who had completed 12 weeks of lorundrostat treatment in the Launch-HTN trial. The primary endpoint was change in automated office systolic blood pressure from baseline to week 48. Safety outcomes included treatment-emergent adverse events, as well as adverse events of interest, which included dose modification for hyperkalemia, hyponatremia, and reductions in kidney function.¹

Of the 808 patients enrolled in Launch-HTN, 632 continued into the open-label extension. Of these patients, 549 completed 48 weeks of treatment, and 583 completed 48 weeks of follow-up. Mean age among this population was 61 years, and mean body mass index (BMI) was 33 kg/m2. Mean baseline blood pressure was 149/87 mmHg, and 59% of patients were taking ≥3 antihypertensive medications.¹

By week 48, Laffin and colleagues noted a least-squares mean change in automated office systolic blood pressure of -17.8 mmHg (95% CI, -19.6 to -16; P <.0001). Additionally, automated office systolic blood pressure was achieved by 24.6%, 56%, and 77.9% of patients, respectively. Mean change in automated office diastolic blood pressure at week 48 was -9.2 mmHg (95% CI, -10.2 to -8.3; P <.0001). The team also found that serum potassium >6 mmol/L occurred in only 2.5% of patients over the 36-week open-label treatment period.¹

Laffin and colleagues ultimately concluded that these data reflect sustained blood pressure control over a long period of lorundrostat treatment, indicating its long-term efficacy. Additionally, its acceptable safety profile from Launch-HTN was echoed in Transform-HTN, positioning it as a safe and tolerable treatment in this population.¹

Laffin also discussed his thoughts on lorundrostat’s future, should it receive regulatory approval. He addressed its position in a field largely dominated by spironolactone, another very effective treatment in this patient population.

“Spironolactone intolerance isn’t uncommon. I use a lot of spironolactone in my practice because they’re approved, they’re good drugs, and they work for resistant hypertension,” Laffin said. “But patients will come in with all these side effects, and they need to be switched to an ASI. Unfortunately, we don’t have direct comparative evidence against spironolactone with lorundrostat – hopefully, at some point in the future, we will.”

Editors’ Note: Laffin reports relevant disclosures with AstraZeneca, Arrowhead, Medtronic, Eli Lilly, Mineralys, Crispr Therapeutics, Novartis, Novo Nordisk, and others.

References

1. Saxena M, Rodman D, Borghi C, et al. Transform-HTN: Long-Term Efficacy and Safety of Lorundrostat, a Novel Aldosterone Synthase Inhibitor, in Uncontrolled Hypertension. Presented at the American Heart Association (AHA) Scientific Sessions 2026, Chicago, IL. November 6-9, 2026.

2. Saxena M, Laffin L, Borghi C, et al. Lorundrostat in participants with uncontrolled hypertension and treatment-resistant hypertension. JAMA. 2025;334(5):409. doi:10.1001/jama.2025.9413