Novel Drug Lowers Stubbornly High BP in Phase 3 Trial

TOPLINE:

Lorundrostat, a novel aldosterone synthase inhibitor, lowered blood pressure among adults with uncontrolled hypertension in a phase 3 trial, including in treatment-resistant cases. Adverse events tended to be mild and resolved without intervention, the investigators reported.

METHODOLOGY:

• Launch-HTN enrolled 1083 participants across 159 clinic sites in 13 countries between November 2023 and September 2024, with follow-up until January 2025.
• The study population included adults with uncontrolled hypertension taking 2-5 antihypertensive medications (46.9% women, 28.7% Black or African American individuals, and 63.3% having a BMI ≥ 30).
• Participants were randomized in a 1:2:1 ratio to receive either 50 mg/d of lorundrostat with possible escalation to 100 mg/d (n = 270), 50 mg/d of lorundrostat (n = 541), or placebo (n = 272) for 12 weeks.
• The primary outcome was change in automated office systolic blood pressure at week 6.

TAKEAWAY:

• Participants who received lorundrostat showed a least-squares mean change in systolic blood pressure of −16.9 mm Hg (95% CI, −19 to −14.9) compared with −7.9 mm Hg (95% CI, −11.5 to −4.2) for those who received placebo (P < .001)
• At week 6, 44.1% of participants who received lorundrostat achieved systolic blood pressure below 130 mm Hg compared to 24.1% of those who received placebo (odds ratio, 3.4; 95% CI, 1.5-7.8; P = .003).
• Treatment efficacy was consistent across age, sex, race, BMI, and number of prescribed antihypertensive medications, the researchers reported.
• Treatment-emergent adverse were predominantly mild or moderate in severity. Prespecified adverse events of hyponatremia, hyperkalemia, or reduction in kidney function led to nine discontinuations among those who received lorundrostat compared with none among those who received placebo. About 2% of participants who received lorundrostat experienced hypotension with symptoms (vs 0.4% of those who received placebo).

IN PRACTICE:

“These data support the use of lorundrostat as a treatment option for participants with uncontrolled hypertension, including treatment-resistant hypertension,” the researchers reported.

SOURCE:

Manish Saxena, MBBS, from Barts Health NHS Trust and Queen Mary University, in London, England, was the corresponding author of the study, which was published online on June 30 in JAMA. Mineralys Therapeutics, the company developing the drug, previously announced top-line results from Launch-HTN in March.

LIMITATIONS:

This study evaluated lorundrostat’s efficacy and safety for only 12 weeks. Longer-term data are being collected in an open-label extension. The researchers used unattended office blood pressure measurements, though ambulatory blood pressure monitoring is considered the gold standard. A phase 2 study measured 24-hour ambulatory blood pressure, however, and “demonstrated similar patterns of [blood pressure] lowering,” they wrote.

DISCLOSURES:

This study was funded by Mineralys Therapeutics. Saxena and some coauthors reported receiving personal fees from Mineralys and other pharmaceutical companies. Some of the authors were employees of Mineralys.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.