lorundrostat (MT-4129) / Mineralys Therapeutics - LARVOL DELTA

Results from the Phase 2 Explore-CKD Trial of lorundrostat, a novel aldosterone synthase inhibitor, in participants with uncontrolled hypertension, chronic kidney disease, and albuminuria. (PubMed, Kidney Int) - "Lorundrostat added to SGLT2i reduced AOSBP and albuminuria in patients with uHTN and CKD, and was associated with an acceptable safety profile. The observed reduction in albuminuria may suggest a potential cardiorenal benefit. However, longer-term studies are needed to determine whether these findings translate into durable kidney or cardiovascular outcomes."

Clinical • Journal • P2 data • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Diabetes • Hypertension • Metabolic Disorders • Nephrology • Renal Disease • Retinal Disorders • Type 2 Diabetes Mellitus • CST3

Pharmacokinetics of novel drugs for the treatment of Diabetic nephropathy. (PubMed, Expert Opin Drug Metab Toxicol) - "Evidence was synthesized for sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), dual incretin agonists, nonsteroidal mineralocorticoid receptor antagonists (nsMRA), endothelin receptor antagonists (ERA), aldosterone synthase inhibitors (vicadrostat, baxdrostat, and lorundrostat), avenciguat, and ziltivekimab, emphasizing exposure, clearance, metabolism, elimination, and dosing implications. In reduced kidney function, SGLT2i show modest exposure increases but attenuated glucose-lowering effects, finerenone shows modest exposure increases despite minimal renal clearance, and ERA may have larger increases that narrow the therapeutic window. Newer incretin therapies generally maintain stable exposure, while eGFR alone may incompletely capture PK risk because uremia, altered protein binding, and nonrenal clearance can influence exposure. The next advance is likely to be drug-specific decision support integrating estimated..."

Journal • PK/PD data • Review • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Comparative Efficacy of Aldosterone-Related Sodium-Retention Pathway Therapies for Resistant Hypertension: A Drug-Level Network Meta-Analysis of Randomized Controlled Trials. (PubMed, J Clin Hypertens (Greenwich)) - "In the primary drug-level analysis, amiloride, spironolactone, baxdrostat, eplerenone, and lorundrostat significantly reduced office systolic BP compared with placebo, with mean differences (MDs) of -14.08, -10.78, -9.09, -8.14, and -6.80 mmHg, respectively. Osilodrostat showed a statistically uncertain effect, with an MD of -2.61 mmHg...MRAs remain the established reference add-on therapy, whereas newer ASIs and amiloride may represent pathway-based alternatives for selected patients. Trial Registration: INPLASY202670099."

Clinical • Journal • Retrospective data • Cardiovascular • Hypertension

Efficacy and safety of lorundrostat in uncontrolled hypertension: a systematic review, meta-analysis, and meta-regression. (PubMed, Ann Med Surg (Lond)) - "Lorundrostat demonstrates significant antihypertensive efficacy and a manageable safety profile in UH patients. Larger, long-term trials are warranted to further validate its safety across broader populations and complete its efficacy profile, emphasizing the unknown long-term cardiovascular outcomes of the intervention."

Journal • Retrospective data • Cardiovascular • Hypertension • Hypotension

24-hour blood pressure burden: aldosterone, cardiorenal risk, and the next generation of blood pressure control (ESC 2026) - "Sponsored by AcademicCME - Supported by an independent educational grant from AstraZeneca To review the physiologic functions of aldosterone and explain how aldosterone excess and dysregulation contribute to sustained day and night time hypertension, nocturnal blood pressure elevation, morning surge, blood pressure variability, and the cumulative 24 hour blood pressure burden that drives cardiovascular and cardiorenal organ damage; To describe how 24 hour ambulatory blood pressure monitoring detects and confirms biologically meaningful blood pressure phenotypes, including nocturnal hypertension, non and reverse dipping, morning surge, and high blood pressure variability, and correlate these ambulatory blood pressure monitoring detected patterns with underlying mechanisms such as renin-angiotensin-aldosterone system activation, aldosterone excess, sodium retention, obstructive sleep apnel, and sympathetic overactivity; To summarise 24 hour and nocturnal blood pressure..."

Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension

Efficacy and safety of selective aldosterone synthase inhibitors for blood pressure reduction in patients with CKD: a meta-analysis of randomized controlled trials. (PubMed, J Hypertens) - "Five RCTs (1,148 patients) were included; 2 used baxdrostat, 2 lorundrostat, and 1 study used vicadrostat. The risk of hyperkalemia was higher with ASIs, but with high heterogeneity (risk ratio, 4.04 [95% CI 0.94 to 17.35], I2 = 76%). In conclusion, selective ASIs present a potential treatment option for BP control and albuminuria reduction in patients with CKD."

Journal • Retrospective data • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Hypertension • Nephrology • Renal Disease

Efficacy and Safety of Selective Aldosterone Synthase Inhibitors in Uncontrolled Hypertension: A Systematic Review and Dose-Specific Network Meta-Analysis of Randomized Controlled Trials. (PubMed, Cardiol Rev) - "Selective aldosterone synthase inhibitors (ASIs), including baxdrostat and lorundrostat, target CYP11B2 while sparing cortisol synthesis, offering a novel strategy for resistant and uncontrolled hypertension. ASIs lowered serum aldosterone and raised plasma renin activity. Safety signals included reduced eGFR (MD -6.91 mL/min/1.73 m2), hyperkalemia [risk ratio (RR) 5.04], hyponatremia (RR 2.11), and symptomatic hypotension (RR 3.17), with dose-dependent risks most pronounced for lorundrostat 100 mg."

Journal • Retrospective data • Cardiovascular • Heart Failure • Hypertension • Hypotension

Selective Aldosterone Synthase Inhibition in Resistant and Uncontrolled Hypertension: Focus on Lorundrostat. (PubMed, J Cardiovasc Pharmacol) - No abstract available

Journal • Cardiovascular • Hypertension

Efficacy and safety of lorundrostat in resistant hypertension: a dose-based systematic review and meta-analysis with GRADE assessment. (ESC 2026) - No abstract available

Retrospective data • Review • Cardiovascular • Hypertension

When Methods Matter: An Umbrella Review of Lorundrostat and the Impact of Analytical Decisions on Reported Blood Pressure and Safety Outcomes. (PubMed, Am J Cardiovasc Drugs) - "Lorundrostat produces a modest blood pressure reduction in uncontrolled hypertension. Current evidence is constrained by methodological heterogeneity, limited long-term data, and inadequate safety reporting. Standardized analytical approaches and greater transparency are essential. The proposed effect size concordance index (ECI) may complement overlap metrics by capturing agreement in effect magnitude and precision; however, further validation is required."

Journal • Review • Cardiovascular • Hypertension

Open-Label Extension (OLE) Study to Assess Safety, Efficacy, and Tolerability of Lorundrostat in Subjects With Hypertension (clinicaltrials.gov) - P3 | N=1076 | Active, not recruiting | Sponsor: Mineralys Therapeutics Inc. | Trial completion date: Dec 2026 ➔ May 2027

Trial completion date • Cardiovascular • Hypertension

Targeting Aldosterone Biosynthesis in Uncontrolled and Resistant Hypertension: A Systematic Review and Meta-Analysis of Randomized Trials of Lorundrostat and Baxdrostat. (PubMed, J Cardiovasc Pharmacol Ther) - "Hyperkalemia emerged as the principal safety concern, whereas serious adverse events were not significantly increased. Larger and longer-term studies are needed to define long-term safety and cardiovascular outcomes."

Clinical • Journal • Retrospective data • Review • Cardiovascular • Hypertension

Effect of Fourth-Line Antihypertensive Therapy on Clinic Systolic Blood Pressure in Resistant Hypertension: A Systematic Review and Meta-Analysis. (PubMed, Blood Press) - "Pairwise comparisons against placebo showed that aldosterone targeted therapies produced the largest reductions in SBP, with lorundrostat (MD -11.70 mmHg [95% CI -16.07, -7.33]) and baxdrostat 2 mg (MD -10.10 [-12.63, -7.58]) showing comparable effects, while baxdrostat 1 mg (MD -8.56 [-11.08 to -6.04]) demonstrated reductions similar in magnitude to spironolactone (MD -7.95 [-10.10, -5.80]). β-blockers, including bisoprolol (MD = -6.71 mm Hg), also demonstrated modest SBP reductions, while aprocitentan 12.5 mg reduced SBP by -3.80 mmHg [-6.65, -0.95]...Significant increases in any adverse events were observed with aprocitentan 25 mg (RR 1.89 [1.39, 2.57]) and doxazosin (RR 1.55 [1.09, 2.20])...Due to transitivity violations across trials, indirect comparative rankings remain invalid. Future trials are required to establish efficacy and assess outcomes."

Journal • Retrospective data • Review • Cardiovascular • Hypertension

New Drugs on the Horizon for Hypertension. (PubMed, Adv Kidney Dis Health) - "This includes the nonselective endothelin receptor antagonist aprocitentan, which was Food and Drug Administration approved in 2024 for uncontrolled hypertension. Aldosterone synthase inhibitors including baxdrostat, lorundrostat, and vicadrostat are in phase 1 or 2 trials for hypertension or chronic kidney disease with evidence of significant blood pressure lowering. Finally, the novel small-interfering RNA-based zilebesiran targeting angiotensinogen represents a new class of antihypertensive medications with durable blood pressure-lowering dosing only every 3 or 6 months. Each of these medications has unique properties that can potentially contribute to improvement in blood pressure control for individual patients and at the population level. Development of these novel antihypertensives promises a welcome set of new options for the treatment of hypertension."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Hypertension • Nephrology • Renal Disease

Safety and Efficacy of Lorundrostat in Uncontrolled Hypertension: A Systematic Review and Meta-Analysis. (PubMed, J Cardiovasc Pharmacol) - "In conclusion, Lorundrostat demonstrates clinically meaningful blood pressure reduction in uncontrolled hypertension compared with placebo, but with an increased risk of electrolyte disturbances and hypotension. Cautious use and close monitoring are warranted, and larger, long-term trials are needed to further define its safety and therapeutic role."

Journal • Retrospective data • Cardiovascular • Heart Failure • Hypertension • Hypotension

Efficacy and Safety of Lorundrostat for Uncontrolled and Treatment-resistant Hypertension: A Systematic Review and Meta-analysis of Randomized Controlled Trials. (PubMed, J Cardiovasc Pharmacol) - "Lorundrostat effectively reduced blood pressure; however, its use was accompanied by increased adverse events, hyperkalemia, and symptomatic hypotension. Efficacy must therefore be weighed carefully against safety, taking into account the patients' baseline characteristics."

Journal • Retrospective data • Cardiovascular • Hypertension • Hypotension

Dose-Response Relationships and Comparative Efficacy of Aldosterone Synthase Inhibitors in Resistant Hypertension: A Comprehensive Network Meta-Analysis and Meta-Regression. (PubMed, J Clin Med) - "This study aimed to synthesize evidence regarding the comparative efficacy, optimal dosing, and dose-response relationships of three ASIs-baxdrostat, lorundrostat, and osilodrostat-for the treatment of resistant hypertension. The strong linear dose-response relationships suggest these agents have a favorable therapeutic window for titration. While effective, clinical implementation requires careful monitoring for adverse events."

Journal • Retrospective data • Review • Cardiovascular • Hypertension

Adrenocortical cell model allowing rapid testing of aldosterone synthase inhibitors. (ENDO 2026) - "ASI activity was examined in the HAC13, HAC15 and HAC50 clones using three ASI: Osilodrostat (30 nM), Baxdrostat (300 nM), and Lorundrostat (300 nM) in 3h incubations with and without DOC. Incubation of adrenal HAC clonal cell lines with DOC acutely enhanced aldosterone production. This approach shortened experimental times needed for testing ASI effects on aldosterone production. These findings support the potential for adrenal cell DOC precursor incubation as a practical and easily applicable approach for early-stage in vitro ASI screening."

Late-breaking abstract • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Solid Tumor

Lorundrostat Modulates Heart Failure Risk Biomarkers in Participants with Uncontrolled Hypertension (ENDO 2026) - "Proteomic analyses suggest that lorundrostat is associated with favorable broad, system-level effects on vascular biology and matrix remodeling networks implicated in HF. Although based on circulating biomarkers rather than clinical HF outcomes, these results provide biological plausibility and support further evaluation of the therapeutic potential of lorundrostat in HFpEF."

Biomarker • Late-breaking abstract • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Metabolic Disorders • MMP2 • NOTCH3 • NRP1 • PDGFRA • PDGFRB • SPON1 • SVEP1

Efficacy and safety of selective aldosterone synthase inhibitors for blood pressure reduction in CKD patients: a systematic review and meta-analysis (ERA 2026) - "Results Five RCTs involving 1,148 patients were included in the analysis for the primary outcome; 2 used baxdrostat, 2 lorundrostat and 1 study used vicadrostat. Image Figure 1. Pooled analyses for the placebo-adjusted SBP change."

Retrospective data • Review • Cardiovascular • Chronic Kidney Disease • Hypertension

Combined Aldosterone Synthase and SGLT2 Inhibition: A Recipe for Success in CKD with Uncontrolled Blood Pressure? (PubMed, Curr Hypertens Rep) - "ASIs such as baxdrostat and lorundrostat demonstrate clinically meaningful reductions in systolic blood pressure, with early evidence suggesting favorable effects on albuminuria. The combination of ASIs and SGLT2 inhibitors represents a mechanistically complementary approach to targeting RAAS dysregulation, volume status, and metabolic pathways. This strategy has the potential to redefine treatment paradigms for CKD-associated uncontrolled hypertension, pending evaluation of long-term outcome benefits."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Hypertension • Nephrology • Renal Disease

Safety and efficacy of lorundrostat, an aldosterone synthase inhibitor, in patients with uncontrolled hypertension: A systematic review and meta-analysis. (PubMed, Medicine (Baltimore)) - "Lorundrostat effectively manages uncontrolled HTN but increases the risk of some AEs. More RCTs involving diverse populations are needed to improve clinical decision-making."

Journal • Retrospective data • Cardiovascular • Hypertension • Hypotension

Aldosterone synthase inhibitors in uncontrolled and resistant hypertension: A phenotype-stratified systematic review and network meta-analysis of randomized trials. (PubMed, PLoS One) - "ASIs provide clinically meaningful BP reduction across both hypertension phenotypes; however, short-term use is associated with hypotension and electrolyte disturbances, necessitating careful monitoring. Phenotype-specific efficacy and long-term safety require validation in outcome-driven trials. Systematic Review Registration: PROSPERO CRD420251266257."

Journal • Retrospective data • Cardiovascular • Heart Failure • Hypertension • Hypotension

Aldosterone synthase inhibitors: a new option for antihypertensive, cardio-renal protection. (PubMed, Hypertens Res) - "In recent years, research into selective aldosterone synthase inhibitors has progressed, resulting in the development of drugs such as baxdrostat, lorundrostat, and vicadrostat. In non-epithelial tissues, aldosterone actions are not major, and ASIs do not affect the physiological actions of cortisol via MR. Further investigation is needed to determine the pharmacological effects of this mechanism, and how it differs from MR antagonists (The recruitment of co-activators and co-repressors in transcriptional activity is omitted)."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Hypertension • Hypotension • Nephrology • Renal Disease

Optimal Dose of Lorundrostat in Uncontrolled Hypertension: A Dose Response Meta-Analysis. (PubMed, Dose Response) - "Lorundrostat effectively lowers BP with a manageable safety profile. The modeling-based insights suggest 60 mg as the optimal dose, delineating a clearer therapeutic window."

Journal • Retrospective data • Cardiovascular • Hypertension