Lorundrostat Significantly Lowers Blood Pressure in Uncontrolled and Resistant Hypertension: Launch-HTN Trial

Uncontrolled hypertension continues to be a significant global health burden, with dysregulated aldosterone production playing a central role in its pathophysiology. Lorundrostat, a new oral medication that inhibits aldosterone synthesis, was assessed for its ability to reduce blood pressure in adults already taking two to five antihypertensive medications.

The study enrolled 1,083 adults across 159 clinical sites in 13 countries between November 2023 and September 2024. Participants had uncontrolled hypertension despite being on standard therapy, and many were classified as having treatment-resistant hypertension. The trial used a 1:2:1 randomization strategy to assign patients to either 50 mg of lorundrostat for 12 weeks, 50 mg with a potential dose escalation to 100 mg at week 6, or a matching placebo.

The primary outcome was the change in automated office systolic blood pressure at six weeks for those on 50 mg of lorundrostat compared with placebo.

The study led to the following findings:

• Participants receiving 50 mg of lorundrostat showed an average reduction in systolic blood pressure of 16.9 mm Hg.
• The placebo group showed a reduction of 7.9 mm Hg.
• The difference between the two groups was −9.1 mm Hg, indicating significant therapeutic benefit.
• The treatment was generally well tolerated with a low incidence of serious side effects.
• Adverse events such as hyperkalemia, hyponatremia, and decreased kidney function were slightly more common in the lorundrostat group.
• Discontinuation due to these adverse events was rare, affecting less than 1% of participants.
• The average age of participants was 61.6 years.
• Women made up 46.9% of the study population.
• Nearly 29% of participants identified as Black or African American.
• Obesity was prevalent, with 63.3% of participants having a BMI of 30 or more.

While the trial demonstrated the short-term efficacy and safety of lorundrostat, the authors noted several limitations. The study period was limited to 12 weeks due to FDA guidance for placebo-controlled hypertension trials. Additionally, unattended office blood pressure readings were used instead of 24-hour ambulatory monitoring, though previous phase 2 data using ambulatory measurements supported similar findings.

Despite these limitations, the researchers concluded that lorundrostat holds promise as an effective option for patients struggling with uncontrolled or treatment-resistant hypertension. Ongoing long-term extension trials aim to further evaluate its sustained efficacy and safety profile.

Reference:

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. Published online June 30, 2025. doi:10.1001/jama.2025.9413