Mineralys Therapeutics' Lorundrostat Trial Recognized in JAMA's Inaugural "Research of the Year" for Treatment-Resistant Hypertension
核心洞察
Mineralys Therapeutics' Phase 3 Launch-HTN trial of lorundrostat was selected as one of nine most impactful studies of 2025 by JAMA editors for its breakthrough approach to treatment-resistant hypertension.
The trial demonstrated that lorundrostat 50 mg once daily achieved significant systolic blood pressure reductions of 16.9 mmHg at Week 6 and 19.0 mmHg at Week 12 when added to existing treatments.
Lorundrostat offers a novel mechanism by inhibiting aldosterone synthase enzyme production rather than blocking hormone receptors, potentially benefiting up to 40% of hypertension patients with uncontrolled disease.
Mineralys Therapeutics announced that its Phase 3 Launch-HTN clinical trial evaluating lorundrostat for treatment-resistant hypertension has been featured in JAMA's inaugural "Research of the Year Roundup," marking a significant recognition for the novel aldosterone synthase inhibitor approach to managing uncontrolled blood pressure.
The Launch-HTN trial, which enrolled 1,083 participants with uncontrolled or treatment-resistant hypertension, represents the largest study of an aldosterone synthase inhibitor conducted in this patient population. JAMA editors selected the study as one of nine most impactful research efforts published between October 2024 and September 2025, profiling it under the banner "New Hope for Treatment-Resistant Hypertension."
Novel Mechanism Targets Root Cause of Hypertension
Lorundrostat distinguishes itself from existing treatments through its unique mechanism of action. While current aldosterone blockers obstruct the hormone receptor, lorundrostat inhibits CYP11B2 (搜索), the enzyme responsible for aldosterone production itself. This approach targets what researchers consider a root cause of hypertension, as dysregulated aldosterone levels drive elevated blood pressure in approximately 30% of all hypertensive patients.
The drug demonstrates remarkable selectivity, with 374-fold preference for aldosterone-synthase inhibition versus cortisol-synthase inhibition in vitro studies. With an observed half-life of 10-12 hours, lorundrostat achieved 40-70% reduction in plasma aldosterone concentration in hypertensive participants during clinical testing.
Significant Blood Pressure Reductions Achieved
The Launch-HTN trial met its primary endpoint with clinically meaningful results. When added to existing background antihypertensive treatment, lorundrostat 50 mg dosed once daily demonstrated statistically significant mean reductions in automated office blood pressure (AOBP). At Week 6, participants experienced a 16.9 mmHg reduction in systolic blood pressure (-9.1 mmHg placebo adjusted; p-value < 0.0001), with sustained benefits showing a 19.0 mmHg reduction at Week 12 (-11.7 mmHg placebo adjusted; p-value < 0.0001).
These benefits remained consistent across diverse patient demographics, including variations in age, sex, race, body mass index, and baseline medication regimens. The trial recruited a notably diverse population with high proportions of female, Black or African American, and elderly participants.
Addressing Critical Unmet Medical Need
JAMA's Executive Editor Gregory Curfman, MD, emphasized the significance of advancing care for patients whose hypertension remains uncontrolled despite multiple medications. He noted that lorundrostat "opens a new approach to the treatment of uncontrolled hypertension, which may affect up to 40% of patients."
Current treatment options leave substantial gaps in care, with less than 50% of hypertension patients achieving their blood pressure goals with available medications. This uncontrolled hypertension carries serious consequences, as patients face heightened cardiovascular risks including myocardial infarction, stroke, and chronic kidney disease.
The economic burden is substantial, with hypertension and related health issues resulting in an estimated annual cost of approximately $219 billion in the United States as of 2019. In 2022, more than 685,000 deaths in the United States included hypertension as a primary or contributing cause.
Safety Profile and Tolerability
The Launch-HTN trial demonstrated a favorable safety and tolerability profile for lorundrostat. While hyponatremia, hyperkalemia, and reduced kidney function occurred more frequently in the treatment arm compared to placebo, discontinuation rates due to adverse events remained below 1%.
The trial design included three treatment arms: placebo, lorundrostat 50 mg once daily, and lorundrostat 50 mg once daily with the option to increase to 100 mg at week six. Participants were adults whose blood pressure remained uncontrolled despite being on two to five antihypertensive medications.
Ongoing Development and Future Prospects
Lorundrostat continues evaluation in the Transform-HTN open-label extension trial, assessing long-term safety and durability of response. Mineralys has also completed enrollment in Explore-OSA, the first trial evaluating lorundrostat in participants with hypertension and moderate-to-severe obstructive sleep apnea. As the only aldosterone synthase inhibitor being studied to address both apnea-hypopnea index and nighttime systolic blood pressure in this population, data is anticipated in the first quarter of 2026.
"We are honored that JAMA has recognized Launch-HTN as one of its Research of the Year studies," said Jon Congleton, Chief Executive Officer of Mineralys Therapeutics. "This acknowledgment underscores the significant clinical need faced by millions of people living with uncontrolled or treatment-resistant hypertension."
The company has completed four successful clinical trials of lorundrostat, including two pivotal registrational trials - the Phase 3 Launch-HTN trial and Phase 2 Advance-HTN trial - supporting robust, durable, and clinically meaningful reductions in systolic blood pressure. These trials may serve as the basis for a new drug application submission to the FDA.