– New analysis on serum leptin levels among patients in the Target-HTN Phase 2 trial adds to emerging evidence of positive feedback loop linking obesity, leptin and aldosterone –
– Excess aldosterone in patients with visceral obesity defines a unique hypertensive endotype with potential for an enhanced response to aldosterone-targeted therapy with lorundrostat –
– Early identification and intervention with lorundrostat may result in improved clinical outcomes for obese patients with uncontrolled or resistant hypertension –
Data previously presented from Target-HTN showed that elevated body mass index (BMI) was predictive of an enhanced reduction in systolic blood pressure (BP) from lorundrostat treatment. The poster presented at the AHA Scientific Sessions 2023 included a new analysis of serum leptin levels among subjects in the trial, which showed that increased BMI was correlated with increased leptin circulation. This is consistent with emerging evidence of a leptin-driven, positive feedback loop between obesity, aldosterone and hypertension.1
“Through our ongoing analyses of data from the Target-HTN trial, a profile of which patients can benefit the most from lorundrostat is emerging. After examining serum leptin levels across participants, we now have evidence that this hormone, along with elevated BMI, could be a biomarker for patients who may experience a meaningful blood pressure reduction from lorundrostat treatment,” stated
A pre-specified analysis from Target-HTN showed that subjects with a BMI >30kg/m2 experienced placebo-adjusted reductions in systolic BP of 16.7mmHg (p=0.002) and 12.3mmHg (p=0.03) with lorundrostat 50mg and 100mg once-daily (QD) doses, respectively. Findings from the new analysis showed that the same BMI range was associated with a 75% increase in mean serum leptin (21.6 ±1.9ng/mL in subjects with a BMI ≤30kg/m2 compared to 37.8 ±2.4ng/mL in subjects with a BMI >30kg/m2; p<0.001), indicating that increased circulating leptin may be a useful biomarker to identify lorundrostat-responsive individuals.
The Target-HTN trial demonstrated that treatment with lorundrostat at doses of 50mg and 100mg QD led to a statistically and clinically significant reduction of systolic BP in uncontrolled hypertensive individuals on at least two background antihypertensive medications. Full results from the trial were published in the
Target-HTN trial results support the transition to late-stage development of lorundrostat as a treatment for uncontrolled or resistant hypertension. The Company’s ongoing pivotal development program for lorundrostat to treat uncontrolled or resistant hypertension is currently enrolling subjects in the pivotal Advance-HTN trial, and the second pivotal trial, Launch-HTN, trial is expected to be initiated in the second half of 2023.
The poster at AHA Scientific Sessions 2023 titled, “Lorundrostat for Treatment of Obesity-Related, Aldosterone-Dependent Hypertension - An Endotype-Specific, Targeted Approach to the Treatment of Uncontrolled Hypertension,” 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 approximately 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 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% 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, CKD 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
References:
1 Faulkner JL, et al. Curr Opin Nephrol Hypertens. 2081;27(2):63-69.
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