Phase 3 Efficacy and Safety Study of a Novel Aldosterone Synthase Inhibitor in Patients with Uncontrolled and Treatment-Resistant Hypertension: Launch-Htn Study

Abstract

Objective: Dysregulated aldosterone plays an important role in the pathophysiology of hypertension. Obesity is a key driver of hypertension and serum aldosterone levels correlate with body mass index (BMI). Aldosterone synthase inhibitors (ASI), a novel class of antihypertensive medications, have shown promise in lowering blood pressure (BP) by targeting aldosterone synthesis in the adrenal glands. The pivotal LAUNCH-HTN phase 3, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of lorundrostat, an ASI, when added to prescribed antihypertensive therapy in patients with uncontrolled hypertension, including treatment-resistant hypertension. Design and method: The study randomized 1,083 patients across 119 global sites. Eligible patients were on 2 to 5 antihypertensive medications, including a thiazide/thiazide-like diuretic, and had unattended automated office systolic BP (AOSBP) of 135-180 mmHg and diastolic BP (AODBP) of 65-110 mmHg. Patients were randomized in a ratio of 1:2:1 to 12 weeks of placebo, 50 mg lorundrostat QD, or 50 mg lorundrostrat QD with up-titration to 100 mg QD if AOSBP was uncontrolled (>=130 mmHg) at 6 weeks. The primary endpoint was a change in AOSBP from baseline at 6 weeks with lorundrostat compared to placebo. Effects of obesity, number of prescribed antihypertensive medications, dose escalation, and proportion of patients achieving BP target (AOSBP <130 mmHg) at 6 weeks were key secondary endpoints. Results: In the study cohort, average age was 62 years, 41% were 65 years or older, 47% were females, 29% were Black or African American, and 59% were on 3 or more prescribed antihypertensive medications. Baseline average (SD) AOBP in the study cohort was 148 (11.9) mm Hg systolic and 87 (9.1) mm Hg diastolic. At baseline 63% of participants had a BMI >=30 kg/m2. The primary efficacy endpoint results will be available in March 2025. Conclusions: The Launch-HTN trial is one of the largest phase 3 studies of a novel treatment in difficult-to-treat patients with hypertension. Participants were on a range of prescribed background antihypertensive treatments that are commonly used in routine clinical practice in the real-world clinical setting. Conclusions pending data.