Lorundrostat lowered blood pressure in two aldosterone-synthase trials

Lorundrostat, an experimental pill that blocks the enzyme the body uses to make aldosterone, lowered blood pressure in two randomised trials of people whose hypertension was not controlled on their existing drugs [s1][s2]. In the larger, phase 3 Launch-HTN trial, automated office systolic pressure fell 16.9 mm Hg on a pooled 50 mg dose against 7.9 mm Hg on placebo — a placebo-adjusted difference of 9.1 mm Hg [s1].

The result matters because it is the second positive read-out for this drug class in a year. Aldosterone-synthase inhibitors are the first genuinely new mechanism for high blood pressure to reach late-stage testing in a generation, and baxdrostat — a different molecule with the same target — was approved by the FDA in May 2026, covered on this site in a new blood-pressure drug that targets a hormone pathway no approved pill had hit [s1]. Lorundrostat now brings a second body of evidence to the same idea.

Why the target is different

Aldosterone tells the kidney to hold on to sodium and water, which raises blood volume and pressure, and it drives fibrosis and inflammation in blood vessels beyond that [s2]. The older drugs that act on this hormone — spironolactone, eplerenone — block the receptor aldosterone binds after it is already circulating. Lorundrostat instead inhibits aldosterone synthase, the enzyme that produces the hormone, cutting the supply rather than the signal [s2]. That distinction is the whole rationale for the class: a large share of hard-to-treat hypertension is driven by aldosterone that conventional regimens never touch.

What the two trials did

Launch-HTN, funded by Mineralys Therapeutics, enrolled 1,083 adults with uncontrolled hypertension, including those meeting the stricter definition of treatment-resistant disease, at 159 sites across 13 countries between November 2023 and September 2024 [s1]. Participants stayed on their prescribed regimen of two to five antihypertensive drugs and were randomised 1:2:1 to a dose-escalation arm, a stable 50 mg daily dose, or placebo for 12 weeks [s1]. Their mean age was 61.6 years, 46.9% were female, 28.7% were Black or African American, and 60.1% were already taking three or more blood-pressure medicines — a genuinely difficult-to-treat population [s1]. The primary outcome was the change in automated office systolic pressure at week 6 for the 50 mg group versus placebo [s1].

Advance-HTN, the earlier phase 2 trial published in the New England Journal of Medicine, used a more rigorous measurement: 24-hour ambulatory pressure, which captures the whole day rather than a single clinic reading and is harder to bias [s2]. It randomised 285 participants — 53% of them Black — who remained hypertensive on a standardised two-to-five-drug regimen to placebo, stable 50 mg lorundrostat, or a dose adjusted up to 100 mg [s2].

What they found

In Launch-HTN, the pooled 50 mg group (n=808) fell 16.9 mm Hg in office systolic pressure at week 6 (95% CI 14.9 to 19.0) against 7.9 mm Hg on placebo (95% CI 4.2 to 11.5), a placebo-adjusted difference of 9.1 mm Hg (95% CI 4.9 to 13.3; P<0.001) [s1]. Advance-HTN, on the sterner ambulatory measure, put the 24-hour systolic fall at 15.4 mm Hg in the stable-dose arm and 13.9 in the dose-adjustment arm against 7.4 on placebo, for placebo-adjusted reductions of 7.9 mm Hg (97.5% CI 13.3 to 2.6) and 6.5 mm Hg (97.5% CI 11.8 to 1.2) [s2]. Two trials, two measurement methods, and a consistent placebo-adjusted effect in the 6-to-9 mm Hg range — a meaningful reduction on top of multiple existing drugs.

The safety cost the mechanism predicts

Blocking aldosterone raises the risk of the electrolyte problems aldosterone normally guards against. In Launch-HTN, hyperkalaemia (high potassium), hyponatraemia (low sodium), and falls in kidney function were all reported more often on lorundrostat than placebo, though treatment-emergent adverse events overall occurred in about half of participants (49.9%) and were mostly mild or moderate; discontinuations for these events were rare [s1]. Advance-HTN gives the sharper number: a potassium level above 6.0 mmol per litre — a level that can disturb heart rhythm — occurred in 5 participants (5%) in the stable-dose arm and 7 (7%) in the dose-adjustment arm, versus none on placebo [s2]. That is the same monitoring burden that has always attended aldosterone-directed therapy, and it is why this is a drug for supervised use, not a casual add-on.

How to read it

The efficacy signal is real and now replicated, but both trials were funded by the drug's maker and both were short — 12 weeks — measuring blood pressure, not the strokes and heart attacks that lowering it is meant to prevent [s1][s2]. A 9 mm Hg office reduction and a 7-to-8 mm Hg ambulatory reduction are clinically worthwhile in people who have run out of options, but whether they translate into fewer cardiovascular events, and how lorundrostat compares head-to-head with baxdrostat or with the cheap generic spironolactone, are questions these studies were not built to answer. The context for what counts as high in the first place is set out in what the blood-pressure numbers mean, and the case for confirming any clinic reading at home in why a validated home cuff matters.

What to watch

The near-term questions are regulatory and comparative: whether lorundrostat files for approval on this package, how its label handles the potassium monitoring, and where it and baxdrostat land relative to each other and to existing drugs once longer outcome trials report. Until then, the honest summary is that a second aldosterone-synthase inhibitor works in the short term on the measure it was designed to move, at a predictable electrolyte cost.

This article describes research and is not medical advice. Decisions about blood-pressure treatment are for patients and their treating clinicians.

Sources

• Lorundrostat in Participants With Uncontrolled Hypertension and Treatment-Resistant Hypertension: The Launch-HTN Randomized Clinical Trial — JAMA, published online 30 June 2025
• Lorundrostat Efficacy and Safety in Patients with Uncontrolled Hypertension (Advance-HTN) — New England Journal of Medicine, 23 April 2025