Emerging Therapies for Treatment-Resistant Hypertension: A Review of Lorundrostat and Related Selective Aldosterone...

Area of Science:

• Cardiovascular Medicine
• Endocrinology
• Pharmacology

Background:

• Hypertension remains a leading cause of cardiovascular disease globally.
• Aldosterone synthase (CYP11B2) plays a key role in the renin-angiotensin-aldosterone system and hypertension.
• Selective aldosterone synthase inhibitors offer a targeted approach to blood pressure management.

Purpose of the Study:

• To evaluate the efficacy and safety of lorundrostat, a novel aldosterone synthase inhibitor, in patients with hypertension.
• To assess the dose-dependent effects of lorundrostat on systolic blood pressure.
• To compare the selectivity of lorundrostat for CYP11B2 inhibition over CYP11B1.

Main Methods:

• The Target-Hypertension (Target-HTN) trial enrolled patients with suppressed plasma renin activity and elevated aldosterone levels.
• Two cohorts were studied: Cohort 1 assessed lorundrostat at 100 mg and 50 mg daily versus placebo.
• Cohort 2 evaluated the 100 mg daily dose of lorundrostat.

Main Results:

• Lorundrostat (100 mg and 50 mg daily) significantly reduced systolic blood pressure compared to placebo in Cohort 1.
• The 100 mg daily dose of lorundrostat also demonstrated a significant reduction in systolic blood pressure in Cohort 2.
• Lorundrostat exhibits greater selectivity for CYP11B2 inhibition compared to CYP11B1, distinguishing it from other inhibitors.

Conclusions:

• Lorundrostat demonstrates significant antihypertensive efficacy in patients with specific hormonal profiles.
• Its selectivity for aldosterone synthase inhibition suggests a potentially favorable safety profile.
• Further Phase 3 trials are warranted to confirm the long-term safety and efficacy of lorundrostat and related selective aldosterone synthase inhibitors.