– Lorundrostat, a highly selective aldosterone synthase inhibitor, demonstrated robust, double-digit reduction in systolic blood pressure (BP), including an enhanced response in individuals with elevated body mass index (BMI) –
– Results simultaneously published in the
– Pivotal clinical program for lorundrostat as a treatment of patients with uncontrolled and resistant hypertension ongoing, with topline data from Advance-HTN and Launch-HTN trials expected in first half of 2024 and mid-2025, respectively –
Target-HTN trial results demonstrate treatment with lorundrostat at doses of 50mg and 100mg once daily (QD) led to a statistically and clinically significant reduction of systolic blood pressure (BP) in inadequately controlled hypertensive individuals on at least two background antihypertensive medications. The reduction in BP was particularly evident among participants with hypertension and concomitant obesity.
“The final results from our Target-HTN trial demonstrate lorundrostat had a robust, double-digit reduction in systolic blood pressure with a well-tolerated profile in the intention-to-treat population of individuals with uncontrolled hypertension and resistant hypertension. In support of our targeted development strategy for lorundrostat, a pre-specified sub-analysis of subjects with elevated BMI demonstrated enhanced reduction in systolic blood pressure that is likely due, in part, to visceral fat driving abnormal aldosterone levels,” stated
Key clinical data from Target-HTN suggest robust BP reductions in the treatment of patients with uHTN and rHTN:
- Target-HTN successfully met its primary endpoint, demonstrating a statistically significant change from baseline in systolic automated office BP (AOBP) with lorundrostat 50mg (n=28) and 100mg (n=25) QD doses versus placebo (n=29):
- -13.7 mmHg systolic AOBP change at 50mg QD, or -9.6 mmHg placebo-adjusted change (p=0.01)
- -11.9 mmHg systolic AOBP change at 100mg QD, or -7.8 mmHg placebo-adjusted change (p=0.04)
- Key secondary endpoint results demonstrated a change in diastolic AOBP of -7.1 mmHg with 50mg QD (or -5.5 mmHg placebo-adjusted change; p=0.02) and -5.8 mmHg with 100mg QD (or -4.1 mmHg placebo-adjusted change; p=0.09)
- Other secondary endpoints, including assessment of 24-hour average BP, supported the efficacy of the QD dosing regimen.
- A pre-specified analysis examined the impact of body mass index (BMI) on the degree of BP lowering with lorundrostat, testing the hypothesis that aldosterone-dependent hypertension may be more significant in obese individuals:
- With 50mg QD, changes in systolic AOBP were 2.2 mmHg in subjects with a BMI 25-30 kg/m2, versus -16.7 in subjects with a BMI ≥30 kg/m2 (placebo-adjusted; p<0.01)
- With 100mg QD, changes in systolic AOBP were -4.5 mmHg in subjects with a BMI 25-30 kg/m2, versus -12.3 in subjects with a BMI ≥30 kg/m2 (placebo-adjusted; p=0.03)
Key safety and tolerability findings from Target-HTN suggest lorundrostat was well‐tolerated with a favorable safety profile, particularly with 50mg lorundrostat QD:
- Lorundrostat was well tolerated at all dose levels
- There was a modest, dose-dependent increase in mean serum potassium (0.25-0.29 mmol/L) and low incidence of elevated serum potassium (3.6% subjects with serum potassium levels above 6.0 mmol/L)
- Three serious adverse events occurred, only one (worsening of pre-existing hyponatremia with 100mg lorundrostat QD) was deemed treatment-related
Target-HTN trial results support the transition to late-stage development of lorundrostat as a treatment for inadequately controlled hypertension. The Company’s ongoing pivotal development program for lorundrostat to treat uHTN and rHTN is currently enrolling subjects in the Advance-HTN trial, and the Phase 3 Launch-HTN trial is expected to be initiated in the second half of the year, with topline data expected in the first half of 2024 and mid-2025, respectively.
The presentation at the 2023 AHA Hypertension Scientific Sessions, titled, “Aldosterone Synthase Inhibition with Lorundrostat for Uncontrolled Hypertension: The Target‐HTN Phase 2 Randomized Clinical Trial,” can be accessed on the publications page of the Mineralys corporate website.
About Target-HTN
The Target-HTN (NCT05001945) Phase 2 proof-of-concept trial was a randomized, double-blind, placebo-controlled, dose-ranging, multicenter trial conducted in the
About Hypertension
Having sustained, elevated blood pressure (or hypertension) increases the risk of heart disease, heart attack and stroke, which are leading causes of death in the
Less than 50 percent of hypertension patients achieve their blood pressure goal with currently available medications. Abnormally elevated aldosterone levels are a key factor in driving hypertension in up to 25 percent of all hypertensive patients.
About Lorundrostat
Lorundrostat is a proprietary, orally administered, highly selective aldosterone synthase inhibitor being developed for the treatment of uncontrolled hypertension and chronic kidney disease (CKD). Lorundrostat was designed to reduce aldosterone levels by inhibiting CYP11B2, the enzyme responsible for its production. Lorundrostat has 374-fold selectivity for aldosterone-synthase inhibition versus cortisol-synthase inhibition in vitro, an observed half-life of 10-12 hours and demonstrated approximately a 70 percent reduction in plasma aldosterone concentration in hypertensive subjects.
About Mineralys Therapeutics
Mineralys Therapeutics is a clinical-stage biopharmaceutical company focused on developing medicines to target hypertension, chronic kidney disease and other diseases driven by abnormally elevated aldosterone. Its initial product candidate, lorundrostat, is a proprietary, orally administered, highly selective aldosterone synthase inhibitor that Mineralys Therapeutics is developing for cardiorenal conditions affected by abnormally elevated aldosterone, including hypertension and CKD. Mineralys is based in
Forward-Looking Statements
Mineralys Therapeutics cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to, statements regarding: the potential therapeutic benefits of lorundrostat; the Company’s expectation that aldosterone synthase inhibitors with an SGLT2 inhibitor may provide additive clinical benefits to patients; the Company’s expectation that the Advance-HTN and the planned Phase 3 clinical trial of lorundrostat may serve as pivotal trials in any submission of a new drug application (NDA) to the
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