Launch-HTN: Lorundrostat Proves Efficacy in Adults with Hypertension, With Manish Saxena, MBBS

Lorundrostat, an aldosterone synthase inhibitor (ASI) in development by Mineralys Therapeutics, has demonstrated its efficacy in lowering blood pressure in adults with uncontrolled hypertension, including those with treatment-resistant hypertension.1

Lorundrostat is a proprietary, orally administered, highly selective ASI in development for the treatment of chronic kidney disease and obstructive sleep apnea in addition to uncontrolled and resistant hypertension. Lorundrostat was designed to lower aldosterone levels by inhibiting the enzyme responsible for its production, CYP11B2. It has 374-fold selectivity for aldosterone-synthase inhibition compared to cortisol-synthase inhibition in vitro and demonstrated a 40-70% reduction in plasma aldosterone concentration in patients with hypertension.2

The editorial team at HCPLive sat down with Manish Saxena, MBBS, deputy clinical co-director of Queen Mary University of London’s William Harvey Heart Center and hypertension specialist at Barts Health NHS Trust, to discuss these results and their implications for hypertension management.

“There’s a lot of focus on 2 things now in blood pressure,” Saxena told HCPLive. “1 is time to target and second is time at target, because that all contributes to cardiovascular risk reduction. Any therapy that really improves blood pressure early, is well tolerated, and has a good safety profile would really help increase the confidence of physicians and patients going in for this therapy.”

Launch-HTN was a double-blind, placebo-controlled, randomized clinical trial, screening participants at 159 sites across 13 countries. The trial involved 3 phases: screening, a 2-week single-blind placebo run-in, and a 12-week randomized, double-blind treatment phase. Participants were then given the option to enroll in an open-label extension of lorundrostat or participate in a 2-week safety follow-up.1

The primary efficacy outcome was change in systolic blood pressure at week 6 for participants randomized to 50 mg of lorundrostat versus placebo. Secondary outcomes included the proportion of participants with a systolic blood pressure <130 mm Hg at week 6 and change in systolic blood pressure at week 6 in patients taking 2 prescribed antihypertensive medications or ≥3 prescribed antihypertensive medications.1

To be eligible for inclusion, participants were required to have a systolic blood pressure of 135-180 mm Hg and a diastolic blood pressure of 65-110 mm Hg, or a diastolic blood pressure of 90-110 mm Hg while taking stable doses of 2-5 prescribed antihypertensive medications. Patients were excluded if they exhibited an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2, a serum potassium level >5.0 mmol/L at screening or >4.8 mmol/L at randomization, or a serum sodium level <135 mmol/L at screening.1

A total of 3161 patients were initially screened; of these, 1575 entered the placebo run-in phase and 1083 entered the treatment phase. This group was randomly assigned in a 1:2:1 ratio to receive either 50 mg of lorundrostat for 6 weeks and then possibly 100 mg for 6 weeks (n = 270) if they met prespecified criteria at week 6, 50 mg of lorundrostat daily for 12 weeks (n = 541), or placebo once daily for 12 weeks (n = 272). Mean age in the treatment phase was 61.6 years (standard deviation [SD], 10.3 years), and 685 (63.3%) had a body mass index ≥30. The last follow-up date was January 24, 2025.1

Least-squares mean change in systolic blood pressure at week 6 was -16.9 mm Hg (95% CI, -19 to -14.9 mm Hg) for the pooled 50 mg of lorundrostat group versus -7.9 mm Hg (95% CI, -13.3 to -4.9 mm Hg, both P <.001) for the placebo group. Lorundrostat’s efficacy was consistent across age, sex, race, BMI, and number of prescribed antihypertensives.1

Saxena also highlighted lorundrostat’s safety profile, noting its lack of effect on other significant systems in the body.

“I think, based on the data we have seen so far, it is highly selective, it’s not disturbing any other pathways in the body,” Saxena said. “That’s very reassuring from a clinical perspective, since it’s only targeting the pathways we want to target without causing any collateral problems in the body.”

According to a press release, Mineralys plans to use the Launch-HTN data to support a New Drug Application in the near future.2

Editor's Note: Saxena reports disclosures with Arrowhead, AstraZeneca, Boehringer Ingelheim, C4 Research, Sanofi, Novartis, and others.

References

1. Saxena M, Laffin L, Borghi C, et al. Lorundrostat in Participants With Uncontrolled Hypertension and Treatment-Resistant Hypertension: The Launch-HTN Randomized Clinical Trial. JAMA. 2025;334(5):409-418. doi:10.1001/jama.2025.9413

2. Mineralys Therapeutics. Mineralys Therapeutics Announces Journal of American Medical Association (JAMA) Publication of Pivotal Phase 3 Launch-HTN Trial for Lorundrostat. June 30, 2025. Accessed October 23, 2025. https://ir.mineralystx.com/news-events/press-releases/detail/74/mineralys-therapeutics-announces-journal-of-the-american