Mineralys Therapeutics, Inc. (NASDAQ: MLYS) has just announced positive topline data from its phase 2 explore-ckd trial evaluating the safety and efficacy of 25 mg of lorundrostat in subjects with hypertension and comorbid chronic kidney disease (CKD). The trial, which met its primary endpoint, demonstrated a 9.3 mmHg reduction in systolic blood pressure and a 7.5 mmHg placebo-adjusted reduction at four weeks, with a statistically significant reduction in the pre-defined endpoint spot urine albumin-to-creatinine ratio of 31%.
In terms of efficacy, the explore-ckd trial showed a 25.60% reduction in spot urine albumin-to-creatinine ratio and a 4.58% reduction in estimated glomerular filtration rate (eGFR). The safety and tolerability profile of lorundrostat was also favorable, with only 3% of subjects experiencing treatment-emergent adverse events leading to discontinuation of the study drug.
The explore-ckd trial was a randomized, double-blind, placebo-controlled, crossover trial, with the primary efficacy endpoint being the change from baseline in systolic blood pressure at week four in the active versus placebo treatment period. The trial also evaluated the change from baseline in urine albumin-to-creatinine ratio and eGFR.
Dr. Matthew Weir, Director of the Division of Nephrology at the University of Maryland Medical Center, emphasized the significance of the trial's findings, stating that "prolonged elevations in blood pressure in patients with compromised renal function can damage the small blood vessels in the kidneys, further reducing their ability to function properly."
Mineralys Therapeutics is positioning lorundrostat as a potential treatment for hypertension and related kidney disease. The company has already completed three trials of lorundrostat for the treatment of subjects with uncontrolled hypertension, including resistant hypertension. These trials demonstrated clinically meaningful reductions in systolic blood pressure and a favorable safety and tolerability profile.
Lorundrostat, a highly selective aldosterone synthase inhibitor, has shown a 40-70% reduction in plasma aldosterone concentration in hypertensive subjects. The drug is being developed for the treatment of uncontrolled or resistant hypertension, as well as CKD and obstructive sleep apnea (OSA).
Mineralys Therapeutics plans to submit a New Drug Application (NDA) based on the positive results from the explore-ckd trial, as well as the successful pivotal trials, launch-htn and advance-htn, and the ongoing open-label extension trial. The company is also conducting the explore-osa trial, which continues to enroll subjects with OSA and uncontrolled hypertension.
These results are particularly significant given the global impact of CKD, affecting more than 10% of the global population, and the estimated 37 million adults in the United States living with CKD. Additionally, hypertension, a leading cause of heart disease, stroke, and mortality, affects a significant proportion of the population, with less than 50% of patients achieving their blood pressure goal with currently available medications.
Mineralys Therapeutics, with its focus on developing medicines to target diseases driven by dysregulated aldosterone, is poised to make a meaningful impact in the treatment of hypertension, CKD, OSA, and other cardiovascular diseases. As a result of these announcements, the company's shares have moved -6.08% on the market, and are now trading at a price of $13.45. Check out the company's full 8-K submission here.
