November 21, 2022 — Mineralys Therapeutics, Inc., a private, clinical-stage biopharmaceutical company committed to developing a novel therapy for the treatment of hypertension and associated cardiovascular diseases, today announced topline results from the Phase 2 Target-HTN trial in individuals with uncontrolled and resistant hypertension. MLS-101, a highly selective investigational aldosterone synthase inhibitor, at doses of 50 mg and 100 mg once daily (QD), met its primary endpoint with statistically significant and clinically meaningful reduction in systolic blood pressure (SBP) in inadequately controlled hypertensive patients on at least two background antihypertensive medications. Robust placebo-adjusted reductions in SBP and diastolic blood pressure (DBP) were observed in the office as well as with 24-hour ambulatory blood pressure monitoring (ABPM) of 24-hour average, night-time, and central blood pressure.
Key clinical data from Target-HTN demonstrated clinically meaningful efficacy in the treatment of patients with uncontrolled and resistant hypertension.
Target-HTN successfully met its primary endpoints, demonstrating statistically significant mean change from baseline in seated automated office SBP versus placebo in the full intent-to-treat analysis. A prespecified sub-analysis demonstrated that blood pressure reduction by MLS-101 was further enhanced in subjects whose background antihypertensive regimen included a thiazide diuretic:
- Placebo-adjusted reduction in SBP of 1.4 mmHg (12.5 mg QD, p=NS), 9.7 mmHg (50 mg QD, p=0.010) and 7.9 mmHg (Part 1, 100 mg QD, p=0.037)
- Thiazide diuretic as part of background medications placebo-adjusted reduction in SBP of 5.3 mmHg (12.5 mg QD, p=NS), 13.2 mmHg (50 mg QD, p=0.010) and 11.4 mmHg (Part 1, 100 mg QD, p=0.028)
Secondary endpoint results, such as DBP and 24-hour ABPM of 24-hour average, night-time, and central blood pressure, were supportive of the primary findings, and will be featured in a future medical publication and medical conference presentation.
Key clinical safety and tolerability findings from Target-HTN of MLS-101 support a safe and well-tolerated profile.
- The data from the Target-HTN trial demonstrated no notable effects on serum cortisol, supporting the selectivity of MLS-101 for aldosterone synthesis.
- Treatment-emergent, serious adverse events were reported in three subjects. Two subjects were deemed unrelated to study drug treatment, and one was deemed to be related to MLS-101 in a subject with worsening of pre-existing hyponatremia that reversed after discontinuation of MLS-101.
- There was an anticipated, modest increase in serum potassium in the two active QD dose cohorts: 0.25 mmol/L in the 50 mg cohort, and 0.35 mmol/L in the 100 mg cohort. Six individuals across the five active dose cohorts experienced an instance of elevated potassium above 6 mmol/L. Per-protocol, study drug administration was reduced, temporarily held or discontinued and consistent with the short half-life of MLS-101; all episodes were rapidly reversible.
- An Independent Data Safety Monitoring Board expressed no concerns about the effect of MLS-101 on serum potassium in the Target-HTN trial.
Target-HTN (NCT05001945) was a Phase 2 randomized, double-blind, placebo-controlled, dose-ranging, multicenter trial conducted in the U.S. The trial was designed to evaluate the safety, efficacy and tolerability of orally administered MLS-101 on blood pressure for the treatment of uncontrolled and resistant hypertension when used as add-on therapy to stable background treatment of two or more antihypertensive agents in 200 male and female subjects 18 years of age or older. Five active doses of MLS-101 (12.5 mg QD, 50 mg QD, 100 mg QD, 12.5 mg twice daily [BID], and 25 mg BID) were compared to placebo in hypertensive subjects.
For more information: https://mineralystx.com/