Mineralys Therapeutics Completes Enrollment in Key Lorundrostat Hypertension Trial

Mineralys Therapeutics, Inc. has successfully reached its enrollment goal of 261 participants for the pivotal Advance-HTN trial. This trial aims to assess the effectiveness and safety of lorundrostat for treating uncontrolled hypertension (uHTN) or resistant hypertension (rHTN) as an add-on to a standard regimen of two or three antihypertensive drugs. Additional participants currently in the screening or run-in phases may still be enrolled in the coming weeks. The company anticipates sharing topline data in the first quarter of 2025.

David Rodman, MD, Chief Medical Officer of Mineralys Therapeutics, expressed enthusiasm about achieving the enrollment target. He emphasized the company’s objective to contribute to significant cardiovascular risk reduction for individuals struggling to maintain optimal blood pressure levels. Rodman expressed optimism that lorundrostat would continue to demonstrate its potential in treating hypertension, as seen in previous trials. He also extended gratitude to the trial investigators and participants for their dedication and commitment.

The Advance-HTN trial is a randomized, double-blind, placebo-controlled Phase 2 clinical trial. It evaluates lorundrostat as an add-on therapy for adults with uHTN or rHTN. Participants who meet the screening criteria will discontinue their current hypertension medications and begin a standard regimen of an angiotensin II receptor blocker (ARB) and a diuretic, or an ARB, diuretic, and calcium channel blocker, depending on their prior medications. Those who remain hypertensive on this regimen are then randomized into three cohorts for a twelve-week treatment: lorundrostat 50 mg once daily (QD), lorundrostat 50 mg QD with an option to titrate to 100 mg QD at week four, or a placebo.

Mineralys Therapeutics will host a virtual Key Opinion Leader (KOL) event on October 30, 2024, to discuss the unmet needs in hypertension treatment and provide an overview of the ongoing lorundrostat clinical program. This event will offer expert insights into the current treatment options for uHTN and rHTN.

Hypertension, characterized by sustained high blood pressure, poses significant risks for heart disease, heart attack, and stroke, which are among the leading causes of death in the U.S. In 2020, hypertension was a primary or contributing factor in over 670,000 deaths in the country. The economic burden of hypertension and related health issues averaged approximately $130 billion annually from 2003 to 2014. Unfortunately, less than half of hypertension patients achieve their blood pressure goals with existing medications. Dysregulated aldosterone levels are a contributing factor in about 25% of hypertensive cases.

Lorundrostat is a proprietary, orally administered aldosterone synthase inhibitor developed for treating uHTN and chronic kidney disease (CKD). The drug works by inhibiting CYP11B2, the enzyme responsible for aldosterone production. In vitro, lorundrostat shows 374-fold selectivity for aldosterone-synthase inhibition over cortisol-synthase inhibition, with a half-life of 10-12 hours. It has been shown to reduce plasma aldosterone concentration by approximately 70% in hypertensive subjects. In the Phase 2 proof-of-concept trial (Target-HTN), lorundrostat demonstrated significant blood pressure reduction in individuals with uHTN, measured both in-office and through 24-hour ambulatory monitoring. Observed adverse events included a slight increase in serum potassium, a decrease in estimated glomerular filtration rate, urinary tract infections, and one serious adverse event of hyponatremia potentially related to the study drug.

Mineralys Therapeutics, based in Radnor, Pennsylvania, is dedicated to developing treatments for hypertension, CKD, and other conditions driven by dysregulated aldosterone. Founded by Catalys Pacific, the company’s primary product candidate is lorundrostat, which is being developed to address cardiorenal conditions impacted by aldosterone dysregulation.