Lorundrostat Shows Promise in Lowering Blood Pressure in Patients With Uncontrolled Hypertension

In a Late-Breaking Clinical Trial presented at ACC.25 in Chicago, the investigational drug lorundrostat significantly lowered systolic blood pressure (SBP) in patients with uncontrolled hypertension. This Phase 2b, double-blind, randomized trial offers encouraging results for a population that often struggles with resistant blood pressure despite multiple medications.

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What Is Lorundrostat?

Lorundrostat is a novel aldosterone synthase inhibitor, targeting a key pathway in blood pressure regulation. Unlike current antihypertensive agents, this drug works by inhibiting aldosterone production, offering a new mechanism for tackling tough-to-control blood pressure.

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Trial Design

• Study Type: Phase 2b, randomized, double-blind

• Participants: 285 patients across 103 U.S. sites

• Demographics:

  • Average age: 60 years

  • 40% women

  • 53% Black patients (a focus group often underrepresented in trials)

• Duration: 12 weeks

• Intervention Arms:

  • Placebo

  • Lorundrostat 50 mg once daily

  • Lorundrostat 50 mg with potential increase to 100 mg at 4 weeks if BP remained uncontrolled

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Inclusion Criteria

Patients were included if they had:

• Uncontrolled hypertension, defined as elevated BP despite treatment with two to five antihypertensive medications

• Stable regimen of standard BP meds for at least three weeks prior to randomization

• Willingness to undergo 24-hour ambulatory blood pressure monitoring (ABPM)

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Exclusion Criteria

Patients were excluded for:

• History of significant renal impairment (e.g., low glomerular filtration rate)

• Hyperkalemia or potassium imbalance at baseline

• Secondary causes of hypertension other than primary aldosteronism

• Recent cardiovascular events (e.g., stroke, MI within last 6 months)

• Current use of mineralocorticoid receptor antagonists (e.g., spironolactone)

• Pregnancy or breastfeeding

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Key Results

At 12 weeks, average reductions in ambulatory SBP were:

• −15.4 mm Hg in 50 mg lorundrostat group

• −13.9 mm Hg in 50–100 mg group

• −7.4 mm Hg in the placebo group

At 4 weeks, 42% of patients in lorundrostat arms had BP under control vs 19% in placebo.

Secondary endpoints (office BP readings) followed similar trends.

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Safety & Tolerability

• Side effects were mild and manageable, including:

  • Mild hyperkalemia in some patients

  • Small declines in GFR (kidney filtration rate)

• No serious safety signals

• Described as well tolerated overall

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Take-Home Points

• Lorundrostat, a new aldosterone synthase inhibitor, showed significant SBP reductions in patients with uncontrolled hypertension.

• Effect was seen as early as 4 weeks, with further reductions by 12 weeks.

• Drug was well tolerated, with manageable effects on potassium and kidney function.

• Racial subgroup analysis showed no differences in efficacy—encouraging for inclusivity.

• More trials are needed, but this agent may become a game-changer in resistant hypertension management.