U.S.-based Mineralys Therapeutics, Inc., announced today (November 16) topline results from its 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, met its primary endpoint with statistically significant and clinically meaningful reduction in systolic blood pressure (SBP) inadequately controlled hypertensive patients on at least two background antihypertensive medications.
Robust placebo-adjusted reductions in SPB 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.
Jon Congleton, chief executive officer of Mineralys, said: “We are very pleased to report that the Target-HTN trial met its primary and secondary endpoints, with MLS-101 demonstrating substantial placebo-adjusted reduction in blood pressure for 24 hours with once-daily, morning dosing.
Mineralys’ primary and secondary endpoint met
“These data reinforce our belief that MLS-101 has the potential to transform the treatment of uncontrolled hypertension, impacting over 30 million individuals in the U.S. alone, by targeting a principal underlying cause, aldosterone. We would like to thank the 200 patients whose participation and commitment to this study was invaluable.”
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.
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.
Sharing additional data
David Rodman chief medical officer of Mineralys, said: “In Target-HTN there was a progressive increase in clinical response as dose and exposure increased with MLS-101 in inadequately controlled or treatment resistant hypertension patients. The blood pressure reduction was substantial and further augmented in individuals using a thiazide diuretic.
“In addition to securing proof-of-concept for MLS-101, clinically meaningful benefit was seen with all doses greater than 12.5 mg per day with maximum reduction in automated office-measured blood pressure seen with 50 mg once daily dose of MLS-101. We look forward to sharing additional data on 24-hour ambulatory assessment of nighttime and central blood pressure in the future.”
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.
MLS-101 phase 2 data
There was an anticipated, modest increase in serum potassium in the two active QD dose cohorts. 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.
Matthew Weir, director of the division of nephrology at the University of Maryland Medical Center, said: “Millions of Americans suffer from the complications and shortened lifespan resulting from inadequately treated hypertension. The MLS-101 phase 2 data support the potential of aldosterone synthase inhibition, an important strategy for blood pressure control.
“MLS-101 has the potential to deliver a differentiated efficacy, safety and tolerability profile compared to mineralocorticoid receptor antagonists, the only other class of antihypertensive to directly target aldosterone biology.”
Target-HTN was designed by Mineralys 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 were compared to placebo in hypertensive subjects.
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