– Lorundrostat, a highly selective aldosterone synthase inhibitor, demonstrated robust, double-digit reduction in systolic blood pressure (BP) with a well-tolerated profile –

– Enhanced reduction in systolic BP seen in individuals with elevated body mass index (BMI) –

– Robust trial design and results led to lorundrostat being first of new class, aldosterone synthase inhibitors, to start pivotal clinical program in hypertension –

RADNOR, Pa., Sept.  10, 2023  (GLOBE NEWSWIRE) -- Mineralys Therapeutics, Inc. (Nasdaq: MLYS), a clinical-stage biopharmaceutical company focused on developing medicines to target hypertension, chronic kidney disease and other diseases driven by abnormally elevated aldosterone, today announced that full results from the Target-HTN Phase 2 trial of lorundrostat, a highly selective aldosterone synthase inhibitor, in individuals with uncontrolled hypertension (uHTN) and treatment-resistant hypertension (rHTN) were published in the Journal of the American Medical Association (JAMA).

"Despite the multitude of currently available treatments, half of all patients treated for hypertension are not able to reach their blood pressure goal. Up to 25 percent of all people with hypertension exhibit abnormal aldosterone levels," said Luke Laffin, M.D., lead investigator and co-director of the Center for Blood Pressure Disorders in the Heart, Vascular & Thoracic Institute at Cleveland Clinic. "Importantly, the Target-HTN study of lorundrostat demonstrated data compelling enough to warrant its advancement into late-stage clinical trials, representing a first-in-class milestone that will further the goal of understanding a new way of treating uncontrolled and treatment-resistant hypertension that takes the underlying causes into account."

In the Target-HTN Phase 2 trial, lorundrostat demonstrated a significant, double-digit reduction in SBP with a well-tolerated profile in the intent-to-treat population of uHTN and rHTN. Subjects with an elevated BMI, and participants taking a thiazide-type diuretic, demonstrated an enhanced reduction in SBP.

The publication notes that blood pressure guidelines recommend similar medication combinations for most patients, regardless of underlying comorbidities or the dominant underlying contributor to hypertension, and that new treatments are needed as management of blood pressure in the U.S. is relatively poor, and hypertension remains a major cause of excess morbidity and mortality.

"We are gratified that JAMA chose to highlight our Target-HTN Phase 2 trial results. These results demonstrated potentially transformative blood pressure reduction in difficult-to-treat hypertension, particularly so in obese individuals, who are known to have elevated aldosterone and suffer from excess cardiovascular morbidity and mortality," stated David Rodman, M.D., Chief Medical Officer for Mineralys. "We believe this trial confirms the link between obesity, excess aldosterone production and hypertension. Based on the beneficial response observed in Target-HTN, our recently initiated pivotal program lays the groundwork to facilitate identification of patients who may benefit from an aldosterone-targeted therapy like lorundrostat."

The trial results support further study of lorundrostat as a treatment for uHTN, including the Company's ongoing pivotal development program for lorundrostat to treat uHTN and rHTN. Under this program, the Company is currently enrolling subjects in the pivotal Advance-HTN trial and expects to initiate the pivotal Launch-HTN trial in the second half of the year, with topline data expected in the first half of 2024 and mid-2025, respectively.

The Target-HTN (NCT05001945) Phase 2 proof-of-concept trial was a randomized, double-blind, placebo-controlled, dose-ranging, multicenter trial conducted in the U.S. The trial was designed to evaluate the safety, efficacy, tolerability and dose response of orally administered lorundrostat for the treatment of uHTN and rHTN 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 lorundrostat (12.5mg once daily QD, 50mg QD, 100mg QD, 12.5mg twice daily [BID], and 25mg BID) were compared to placebo in hypertensive subjects. Pharmacokinetic, pharmacodynamic and response data established that a once-daily dosing regimen was optimal. Adverse events observed were a modest increase in serum potassium, decrease in estimated glomerular filtration rate, urinary tract infection and hypertension with one serious adverse event possibly related to study drug being hyponatremia.