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Last update 20 Mar 2025

Spironolactone

Last update 20 Mar 2025

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

SummarySpironolactone, also known by the trade name ALDACTONE®, is a drug that works as a mineralocorticoid receptor (MR) antagonist. It was first approved by Pfizer Inc. in the United States in 1960. ALDACTONE oral tablets contain 25 mg, 50 mg, or 100 mg of the aldosterone antagonist spironolactone, which is a specific pharmacologic antagonist of aldosterone. Spironolactone acts primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. This causes increased amounts of sodium and water to be excreted, while potassium is retained. Spironolactone is indicated for heart failure, hypertension, edema associated with hepatic cirrhosis or nephrotic syndrome, and primary hyperaldosteronism. It acts as a diuretic and an antihypertensive drug and may be given alone or with other diuretic agents that act more proximally in the renal tubule.

Drug Type

Small molecule drug

Synonyms

Spironolactone (JP17/USP/INN), Spironolattone

+ [8]

Target

Action

antagonists

Mechanism

MR antagonists(Mineralocorticoid receptor antagonists)

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesDigestive System Disorders+ [3]

Active Indication

Myocardial InfarctionStrokeNephrotic Syndrome+ [8]

Inactive Indication-

Originator Organization

G.D. Searle & Co., Inc.

Active Organization

Pfizer Japan, Inc.

Sinopharm Wuhan ZhongLian SiYao Pharmaceutical Co., Ltd.Nova Laboratories Ireland Ltd.

+ [2]

Inactive Organization

CMP Pharma, Inc.

Drug Highest PhaseApproved

First Approval Date

(01 Jan 1959),

EdemaHeart FailureHyperaldosteronism+ [2]

RegulationOrphan Drug (United States)

Structure/Sequence

Molecular FormulaC24H32O4S

InChIKeyLXMSZDCAJNLERA-ZHYRCANASA-N

CAS Registry52-01-7

319

Clinical Trials associated with Spironolactone

ChiCTR2500096253

/ SuspendedNot ApplicableIIT

Effect of 5% minoxidil foam in combination with spironolactone in the treatment of female pattern hair loss

Start Date01 Feb 2025

Sponsor / Collaborator

Xiangya Hospital Central South University

CTR20244928

/ CompletedNot Applicable

螺内酯片在健康受试者中随机、开放、单剂量、两制剂、交叉对照空腹和餐后状态下的生物等效性研究

[Translation] A randomized, open-label, single-dose, two-formulation, crossover controlled bioequivalence study of spironolactone tablets in healthy subjects under fasting and fed conditions

主要目的：研究空腹及餐后状态下单次口服受试制剂螺内酯片（规格：25mg，浙江亚太药业股份有限公司生产）与参比制剂螺内酯片（Aldactone®，规格：25mg，Pfizer Inc公司持证）在健康成年受试者体内的药代动力学，评价空腹及餐后状态下口服两种制剂的生物等效性。

[Translation]

Main objective: To study the pharmacokinetics of the test preparation spironolactone tablets (specification: 25 mg, produced by Zhejiang Asia Pacific Pharmaceutical Co., Ltd.) and the reference preparation spironolactone tablets (Aldactone®, specification: 25 mg, certified by Pfizer Inc.) in healthy adult subjects after a single oral dose in the fasting and fed state, and to evaluate the bioequivalence of the two preparations when taken orally in the fasting and fed state.

Start Date02 Jan 2025

Sponsor / Collaborator

Zhejiang Yatai Pharmaceutical Co., Ltd.

NCT03593317

/ RecruitingPhase 2IIT

Blockade of the Renin-angiotensin-aldosterone System in Patients with ARVD: a Double-blind Multicentre Prospective Randomized Study.

Arrhythmogenic right ventricular dysplasia (ARVD) is a rare cardiomyopathy characterized by the progressive replacement of cardiomyocytes by fatty and fibrous tissue in the right ventricle (RV). These infiltrations lead to cardiac electrical instability and ventricular arrhythmia.
Current treatment for ARVD is empirical and essentially based on treatment of arrhythmia. Thus, there is no validated treatment that will prevent the deterioration of the RV function in patients with ARVD.
The investigator's hypothesis is that the use of anti-fibrotic medications will prevent or at least reduce the deterioration of the RV function. The aim of this project is to evaluate the effect of spironolactone, a Potassium-sparing diuretic on ventricular myocardial remodeling and on arrhythmia burden in patients with ARVD.
The trial is a double-blind parallel multicenter prospective randomized phase II drug study. Patients will be randomized in the two groups: spironolactone or placebo. 13 centers in France will enroll the 120 patients (60 per group). Patients will be followed for 3 years (6 months, 1 year and 3 years) with all examinations (ECG, HA ECG, 24-hour Holter, trans-thoraciqc echocardiography (TTE), biological analyses) according to standard of care. A decrease in right and/or left ventricular deterioration and in arrhythmia burden are expected in ARVD patients treated with spironolactone. This reduction will improve the quality of life of patients and will reduce the number of hospitalizations and the risk of terminal heart failure.

Start Date20 Dec 2024

Sponsor / Collaborator

Hospices Civils de Lyon

100 Clinical Results associated with Spironolactone

100 Translational Medicine associated with Spironolactone

100 Patents (Medical) associated with Spironolactone

11,592

Literatures (Medical) associated with Spironolactone

01 Apr 2025·Journal of Hypertension

Prevalence and correlates of uncontrolled hypertension and cardiovascular morbidity among patients with hypertension at the largest tertiary care hospital in Sri Lanka

Article

Author: Webb, David J. ; Manchanayake, Minura ; Perera, Thilina ; Ranasinghe, Priyanga ; Liyanage, Sandamini

Introduction:Hypertension is the leading preventable cause of cardiovascular morbidity and mortality globally, with a disproportionate impact on low-income and middle-income countries like Sri Lanka. Effective blood pressure (BP) control improves outcomes in patients with hypertension. This study aimed to assess the prevalence of uncontrolled hypertension, and its correlates among Sri Lankan patients with hypertension in clinic settings.Methods:A cross-sectional study was done at the largest tertiary care hospital in Sri Lanka and patients with hypertension presenting to its medical clinics over a 6-month period were recruited. An interviewer-administered questionnaire captured sociodemographic, morbidity, and medication details from records. BP measurements were taken following standard guidelines with OMRON-X7 BP monitors. Multivariate logistic regression was used to identify significant associations (P < 0.05).Results:Among 600 patients (mean age 64 ± 9 years, 43% men), 55% had uncontrolled hypertension. Most (62%) were on 1 or 2 antihypertensives, primarily renin–angiotensin blockers (91%), with minimal (<10%) thiazide use. Uncontrolled hypertension was less common among furosemide (10.5%) and spironolactone (21.5%) users but frequent among those on alpha-blockers (16.3%). Coronary artery disease (58%), heart failure (9%), and stroke (17%) were more common in men and those with longstanding hypertension. Beta-blockers were favoured in those with cardiac comorbidities, and dihydropyridines in those with stroke. Potential treatment resistance, seen in 11%, was associated with increased cardiac morbidity, while sociodemographic factors and family history had no significant impact on BP control or cardiovascular morbidity.Conclusion:Uncontrolled hypertension and cardiovascular morbidity were highly prevalent. The data suggest the need for optimized antihypertensive regimens, with reduced use of alpha-blockers and early and prioritized incorporation of diuretics.

01 Mar 2025·Acta Physiologica

Blocking the mineralocorticoid receptor prevents cardiac and mitochondrial dysfunction through the activation of NOX‐4 in female hormone deprivation rats

Article

Author: Ximenes, Carolina F. ; Eliezeck, Marcos ; Rodrigues, Samya Mere L. ; Varner, Kurt J. ; Scalzo, Sergio ; Ronconi, Karoline ; Ribeiro, Eduardo Hertel ; Rodrigues, Nathália ; Monteiro, André ; Stefanon, Ivanita ; Guatimosim, Silvia ; Costa, Anna Karolina Nascimento ; Vieira, Livia Barroca ; Sanches, Bruno ; da Silva, Maria Luiza Yago ; Fernandes, Aurélia Araújo ; Ferreira, Katyana K. S. ; Spalenza, Thiago

AbstractAimYoung women exhibit lower rates of cardiovascular disease (CVD) than age‐matched men, a protective effect often attributed to estrogen's influence on cardiac and mitochondrial function. The risk of CVD increases in post‐menopausal women, likely due to estrogen deficiency and aldosterone's negative effects, including those on mitochondria and other cellular targets. This study aimed to explore the link between estrogen deficiency and mitochondrial dysfunction in cardiac health. We hypothesized that in estrogen‐deprived conditions, aldosterone could stimulate NADPH oxidase, leading to mitochondrial dysfunction, and reduced cardiac contractility.MethodsWistar rats were divided into four groups: Sham, Ovariectomy‐induced hormone deprivation (Ovx), Ovx with apocynin treatment, and Ovx with spironolactone treatment for 60 days.ResultsBoth apocynin and spironolactone countered the adverse effects of hormone deprivation by preserving myocardial contractility, improving cellular responses to calcium and isoproterenol, and normalizing the expression of key mitochondrial proteins. These compounds also attenuated the increase in reactive oxygen species (ROS) and maintained mitochondrial respiration rates.ConclusionWe concluded that estrogen deficiency contributes to cardiac oxidative stress via the NADPH oxidase and mitochondrial pathways. Apocynin and spironolactone offer significant protective effects, opening new avenues for treating cardiac issues related to estrogen deficiency.

01 Mar 2025·American Journal of Kidney Diseases

Another Note of Caution for Spironolactone: Implications of the BARACK-D Study

Author: Kumar, Akshat U ; Rifkin, Dena E

News (Medical) associated with Spironolactone

15 Oct 2024

·www.biospace.com

Lantern Pharma’s Investigational Drug-Candidate, LP-184, Receives Fast-Track Designation in Glioblastoma from the FDA

Fast Track Designation is designed to expedite FDA review of important new drugs to treat serious conditions and fill an unmet medical need. Fast Track Designation for LP-184 (STAR-001) recognizes Glioblastoma (GBM) as a serious condition impacting more than 13,000 U.S. adults each year and approximately 300,000 globally. A phase 1b/2a clinical trial for recurrent GBM is targeted to start in late 2024/early 2025. LP-184, which will be developed as STAR-001 for CNS and other neuro-oncology indications by Starlight Therapeutics , a wholly owned subsidiary of Lantern Pharma, has the potential to be the first new drug for treating GBM in more than 20 years. DALLAS--(BUSINESS WIRE)--Lantern Pharma Inc. (NASDAQ: LTRN), an artificial intelligence (AI) company dedicated to developing cancer therapies and transforming the cost, pace, and timeline of oncology drug discovery and development, today announced that the FDA has granted Fast Track Designation for investigational drug candidate, LP-184, for treatment of Glioblastoma. LP-184 is currently in a Phase 1A clinical trial designed to evaluate the safety and tolerability of the synthetically lethal investigational drug candidate in a broad range of solid tumors, including Glioblastoma (GBM) . LP-184 was optimized and advanced in part with Lantern’s AI platform, RADR®, to aid in the validation of mechanisms that could be exploited in the clinical setting to eradicate challenging cancers, and uncover insights in targeted patient populations. RADR® is Lantern’s AI platform for cancer therapy discovery, development and rescue with over 100 billion data points and aiding in the development of both Lantern’s portfolio and development initiatives with Lantern’s collaborators. About GBM and the need for improved and novel therapies. Glioblastoma (GBM) affects nearly 13,000 patients annually in the US and approximately 300,000 globally, with a mortality rate of 94%. Current standard of care therapies result in a life expectancy in GBM patients of less than 15 months. A major limitation to development of new drugs in the treatment of GBM is the need for potential drugs to have the ability to cross the blood brain barrier (BBB) as well as the ability to counteract the inherent and adaptive resistance of GBM cancer cells to temozolomide, the current standard of care in GBM. This resistance is largely derived from the expression of the DNA repair enzyme MGMT 1 . LP-184 activity is agnostic to MGMT expression, meaning it does not depend on the under or over-expression of MGMT in GBM and has shown in-vivo, preclinical activity in both types of GBM models. No new drugs for GBM have been approved in over two decades. Lantern Pharma is advancing LP-184, a molecule which demonstrates synthetic lethality when combined with agents that cause DNA damage repair deficiency. 2 Additionally, LP-184 has shown that it causes double-stranded breaks in the DNA of recurrent GBM (rGBM) cancer cells in multiple in-vivo models and is currently being advanced in early clinical stage studies. “Receiving FDA Fast Track Designation for Lantern Pharma’s LP-184 in GBM reinforces our belief that this drug-candidate can help in the critical need to find effective treatment options for patients with GBM and further supports the potential of LP-184 to address the challenges in aggressive CNS cancers, where patients have a critical need for novel and life extending therapies” said Panna Sharma, President and CEO of Lantern Pharma. Current status of LP-184 & STAR-001 in clinical trials & development LP-184 is currently being studied in a phase 1A clinical trial to evaluate the safety, tolerability and maximum tolerated dose (MTD) of the potential therapy in a wide range of tumors, including GBM. The full study design can be viewed here (clinicaltrials.gov) . Once the MTD has been established, Lantern has plans to advance the drug-candidate LP-184 as STAR-001 through its wholly owned subsidiary, Starlight Therapeutics, in GBM and other CNS and brain cancers. Lantern also anticipates further using RADR® to determine potential additional suitability for LP-184 in combination with other approved agents for the control of cancer progression in multiple other patient subgroups. Lantern has provided information on the development of LP-184 in GBM and has also discussed its plan to advance STAR-001 (LP-184 for CNS cancers) in multiple publicly available webinars, including on: June 26, 2024 — STAR-001 in Multiple Brain and CNS Cancers with Dr. Marc Chamberlain, and July 31, 2024 — Born from AI, Lighting The Way in CNS Cancer Treatment with Mr. Panna Sharma. The proposed goals for the development of Phase 1b/2a clinical studies are targeting a rGBM specific trial to begin in late 2024 or early 2025. This trial is being planned to assess LP-184 in a Phase 1b/2a study as mono-therapy and in combination with spironolactone in rGBM to assess safety, pharmacokinetics and preliminary efficacy. Concurrently, Lantern will conduct a retrospective correlative analysis of multiple key markers of DNA damage as exploratory endpoints. EGFR expression or mutation status, MGMT status and expression of DNA damage repair pathway are also planned to be studied as potential response predictors to help inform and guide future late-stage trials and to stratify enrollment. About the FDA Fast Track process The FDA’s Fast Track process is designed to facilitate development and expedite the review of therapies intended to treat serious conditions and address unmet medical needs to potentially bring important new medicines to patients sooner. Companies whose programs are granted Fast Track Designation are eligible for more frequent interactions with the FDA during clinical development. For more information on Fast Track designation, please visit the FDA’s website at . About Lantern Pharma: Lantern Pharma (NASDAQ: LTRN) is an AI company transforming the cost, pace, and timeline of oncology drug discovery and development. Our proprietary AI and machine learning (ML) platform, RADR ® , leverages over 100 billion oncology-focused data points and a library of 200+ advanced ML algorithms to help solve billion-dollar, real-world problems in oncology drug development. By harnessing the power of AI and with input from world-class scientific advisors and collaborators, we have accelerated the development of our growing pipeline of therapies that span multiple cancer indications, including both solid tumors and blood cancers and an antibody-drug conjugate (ADC) program. On average, our newly developed drug programs have been advanced from initial AI insights to first-in-human clinical trials in 2-3 years and at approximately $1.0 - 2.5 million per program. Our lead development programs include a Phase 2 clinical program and multiple Phase 1 clinical trials. We have also established a wholly-owned subsidiary, Starlight Therapeutics, to focus exclusively on the clinical execution of our promising therapies for CNS and brain cancers, many of which have no effective treatment options. Our AI-driven pipeline of innovative product candidates is estimated to have a combined annual market potential of over $15 billion USD and have the potential to provide life-changing therapies to hundreds of thousands of cancer patients across the world. Please find more information at: Website: LinkedIn: X: @lanternpharma Forward-looking Statements: This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements include, among other things, statements relating to: future events or our future financial performance; the potential advantages of our RADR ® platform in identifying drug candidates and patient populations that are likely to respond to a drug candidate; our strategic plans to advance the development of our drug candidates and antibody drug conjugate (ADC) development program; estimates regarding the development timing for our drug candidates and ADC development program; expectations and estimates regarding clinical trial timing and patient enrollment; our research and development efforts of our internal drug discovery programs and the utilization of our RADR ® platform to streamline the drug development process; our intention to leverage artificial intelligence, machine learning and genomic data to streamline and transform the pace, risk and cost of oncology drug discovery and development and to identify patient populations that would likely respond to a drug candidate; estimates regarding patient populations, potential markets and potential market sizes; sales estimates for our drug candidates and our plans to discover and develop drug candidates and to maximize their commercial potential by advancing such drug candidates ourselves or in collaboration with others. Any statements that are not statements of historical fact (including, without limitation, statements that use words such as “anticipate,” “believe,” “contemplate,” “could,” “estimate,” “expect,” “intend,” “seek,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “target,” “model,” “objective,” “aim,” “upcoming,” “should,” “will,” “would,” or the negative of these words or other similar expressions) should be considered forward-looking statements. There are a number of important factors that could cause our actual results to differ materially from those indicated by the forward-looking statements, such as (i) the risk that our research and the research of our collaborators may not be successful, (ii) the risk that observations in preclinical studies and early or preliminary observations in clinical studies do not ensure that later observations, studies and development will be consistent or successful, (iii) the risk that we may not be successful in licensing potential candidates or in completing potential partnerships and collaborations, (iv) the risk that none of our product candidates has received FDA marketing approval, and we may not be able to successfully initiate, conduct, or conclude clinical testing for or obtain marketing approval for our product candidates, (v) the risk that no drug product based on our proprietary RADR ® AI platform has received FDA marketing approval or otherwise been incorporated into a commercial product, and (vi) those other factors set forth in the Risk Factors section in our Annual Report on Form 10-K for the year ended December 31, 2023, filed with the Securities and Exchange Commission on March 18, 2024. You may access our Annual Report on Form 10-K for the year ended December 31, 2023 under the investor SEC filings tab of our website at or on the SEC’s website at . Given these risks and uncertainties, we can give no assurances that our forward-looking statements will prove to be accurate, or that any other results or events projected or contemplated by our forward-looking statements will in fact occur, and we caution investors not to place undue reliance on these statements. All forward-looking statements in this press release represent our judgment as of the date hereof, and, except as otherwise required by law, we disclaim any obligation to update any forward-looking statements to conform the statement to actual results or changes in our expectations. 1 In patients with glioblastoma (GBM) an aggressive and severe type of brain tumor, the cancer medicine temozolomide is more effective in those with a methylation of the gene’s promoter . Overall, MGMT methylation or hyper-methylation is associated with prolonged patient survival in clinical prediction models, while under-methylation or no-methylation can be derived as a result of exposure to temozolomide and cause resistance to temozolomide therapy and therefore no benefit from the use of temozolomide in GBM. 2 Bachchu Lal, Aditya Kulkarni, Joseph McDermott, Rana Rais, Jesse Alt, Ying Wu, Hernando Lopez-Bertoni, Sophie Sall, Umesh Kathad, Jianli Zhou, Barbara S. Slusher, Kishor Bhatia, John Laterra; Preclinical Efficacy of LP-184, a Tumor Site Activated Synthetic Lethal Therapeutic, in Glioblastoma. Clin Cancer Res 15 October 2023; 29 (20): 4209 4218. Contacts Investor Relations mailto: ir@lanternpharma.com ph: (972) 277-1136

Phase 1Fast Track

03 Sep 2024

·synapse.patsnap.com

Cardiovascular Mortality Risk Reduced by 16%! Bayer Announces Latest Analysis Data from Finerenone FINE-HEART Study

On September 1, 2024, at the European Society of Cardiology (ESC) Congress, Bayer published the pooled analysis of the Phase III FINE-HEART study on finerenone, along with the latest data from the FINEARTS-HF trial. The results showed that finerenone significantly reduces all-cause mortality, cardiovascular, and renal outcomes. The findings were simultaneously published in 《Nature Medicine》. About the FINE-HEART StudyFINE-HEART is a pooled patient-level analysis, incorporating the FINEARTS-HF, FIDELIO, and FIGARO studies. This analysis aims to explore the impact of finerenone (brand name: Kerendia/Firialta) on cardiovascular and renal outcomes in approximately 19,000 patients with heart failure (HF) and/or chronic kidney disease (CKD) and type 2 diabetes (T2D), including those with a high burden of comorbidities—a characteristic of HF patients with left ventricular ejection fraction (LVEF) ≥40%. The FIDELIO-DKD and FIGARO-DKD trials randomized approximately 13,000 CKD and T2D patients with albuminuria (UACR≥30mg/g) from 48 countries. FINEARTS-HF included around 6,000 patients from 37 countries with symptomatic HF, LVEF ≥40%, elevated natriuretic peptides, and structural heart disease evidence. The results indicated: Primary Endpoint: ··Finerenone vs. Placebo: Cardiovascular (CV) mortality was numerically lower but not statistically significant (11% relative risk reduction, HR 0.89 [95% CI, 0.78-1.01; p=0.076]). ·Pre-specified Sensitivity Analysis: Involving CV death and unspecified death, finerenone reduced relative risk by 12% (HR 0.88 [95% CI, 0.79-0.98; p=0.025]). ·The effect of finerenone on cardiovascular (CV) death was generally consistent across the six subgroups. ·Compared to placebo, finerenone significantly reduced all-cause mortality as well as cardiovascular and renal outcomes. Secondary Endpoints: ·All-Cause Mortality Reduction: 9% (HR 0.91 [95% CI, 0.84-0.99; p=0.027]). ·Composite Renal Endpoint Reduction: Including time to first occurrence of renal failure, sustained eGFR decline ≥50% (≥4 weeks), or renal death, reduced by 20% (HR 0.80 [95% CI, 0.72-0.90; p<0.001]).HF Hospitalization Reduction: 17% (HR 0.83 [95% CI, 0.75-0.92; p<0.001]). About FinerenoneFinerenone (BAY948862) is an investigational non-steroidal selective mineralocorticoid receptor antagonist (MRA) that can block the overactivation of mineralocorticoid receptors (MR). Overactivation of MR can lead to fibrosis and inflammation, contributing to permanent structural damage in the kidneys. In July 2021, the FDA approved finerenone to reduce the risk of renal failure, slow down the decline in estimated glomerular filtration rate (eGFR), reduce cardiovascular death, non-fatal myocardial infarction, and hospitalization due to heart failure in patients with T2D and CKD. FINEARTS-HF Study:A randomized, double-blind, placebo-controlled, multi-center, event-driven Phase III clinical trial for patients diagnosed with symptomatic heart failure (NYHA class II-IV) and LVEF ≥40% measured within the past 12 months, who also received at least 30 days of diuretics before randomization. According to the latest data disclosed at the 2024 ESC, finerenone significantly reduced the risk of cardiovascular death and total HF events (defined as HF hospitalization or urgent HF visits), by 16% (RR 0.84 [95% CI, 0.74-0.95; p=0.0072]). Approximately half of the HF patients had mildly reduced or preserved LVEF. Finerenone is the first MRA to demonstrate clear cardiovascular benefits in this category of heart failure patients in a Phase III study. Based on these positive results, Bayer plans to discuss regulatory applications with the FDA to expand finerenone's indications. FIGARO-DKD:In August 2021, Bayer announced that finerenone achieved its primary endpoint in the Phase 3 clinical trial FIGARO-DKD, conducted among patients with type 2 diabetes and chronic kidney disease (CKD). Unlike previous Phase 3 trials, FIGARO-DKD primarily included patients with milder CKD classified as stages 1-2. In this study, finerenone reduced the risk of the first occurrence of cardiovascular death or non-fatal cardiovascular events by 13% in type 2 diabetes patients with CKD who were already receiving the maximum tolerated dose of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). FIDELIO-DKD:The FIDELIO-DKD study is a randomized, double-blind, placebo-controlled, parallel-group, multicenter, event-driven Phase 3 clinical trial. It enrolled patients with type 2 diabetes and CKD (including 372 Chinese patients) who were randomly assigned in a 1:1 ratio to receive either finerenone or placebo once daily. According to the data prominently released at the American Society of Nephrology's Kidney Week in 2020, finerenone significantly reduced the risk of the composite renal endpoint by 18% compared to placebo (HR=0.82, 95% CI 0.73-0.93, P=0.001), and significantly reduced the risk of the composite cardiovascular endpoint by 14% (HR=0.86, 95% CI 0.75-0.99, P=0.03). Four months of treatment with finerenone led to a 31% reduction in the urine albumin-to-creatinine ratio from baseline, which remained consistently low, significantly reducing the secondary renal endpoint (HR=0.76; 95% CI 0.65-0.90). Additionally, multiple studies are underway to investigate the broader use of finerenone in heart failure and chronic kidney disease patients, including the MOONRAKER project and the FIND-CKD study. The MOONRAKER project encompasses four studies—FINEARTS-HF, REDEFINE-HF, CONFIRMATION-HF, and FINALITY-HF—involving over 15,000 patients. It is one of the largest heart failure research projects to date, aiming to evaluate the efficacy and safety of finerenone in a wide range of heart failure patients, including those with HFrEF, HFmrEF, HFpEF, and heart failure patients regardless of left ventricular ejection fraction. The FIND-CKD study is a multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial. It will include non-diabetic CKD patients from 270 centers across 19 countries, including China. The study aims to explore the efficacy and safety of finerenone as an add-on therapy to guideline-recommended treatments for non-diabetic chronic kidney disease. About Mineralocorticoid Receptor Antagonists:Mineralocorticoids are a class of steroid hormones secreted by the zona glomerulosa of the adrenal cortex, with aldosterone being the most common. Aldosterone secretion is regulated by various factors, mainly including the renin-angiotensin-aldosterone system (RAAS), as well as other influences such as adrenocorticotropic hormone, sodium (Na+), and potassium (K+) levels. When the concentration of Na+ in the tubular fluid decreases, blood pressure drops, or renal blood flow decreases, these factors stimulate the release of renin into the bloodstream, activating angiotensin II, which, in turn, stimulates the synthesis and secretion of aldosterone. Aldosterone enhances Na+-K+ exchange and increases membrane permeability to Na+, promoting the reabsorption of Na+ in the renal tubules, accompanied by increased water reabsorption, thereby maintaining water and electrolyte balance. However, excessive aldosterone release can cause metabolic disturbances, including hypokalemia and sodium/water retention. It also promotes the generation of inflammatory factors, leading to inflammation and fibrosis in target organs. Additionally, excessive aldosterone can over-activate the mineralocorticoid receptor (MR) and mediate pathological damage to target organs. Aldosterone binds to mineralocorticoid receptors (MR) to exert its effects. MR is widely distributed in multiple tissues, playing a significant role in local substance metabolism and the regulation of pathological injuries, with the most notable expression in the kidneys and cardiovascular system. Overactivation of MR promotes the generation of reactive oxygen species (ROS) and triggers the activation of pro-inflammatory transcription factors such as activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB), leading to inflammatory responses. Furthermore, MR overactivation participates in the expression of pro-fibrotic molecules, including transforming growth factor-β1 (TGF-β1) and plasminogen activator inhibitor-1 (PAI-1), which collectively promote tissue fibrosis. In addition to triggering inflammation and fibrosis, MR overactivation can activate the immune system, leading to leukocyte infiltration among other responses. In the kidneys, overactivation of MR exacerbates oxidative stress, inflammation, and fibrosis, inducing podocyte injury and constricting glomerular vessels, which leads to a gradual decline in renal function, ultimately progressing to end-stage renal disease (ESRD). In the heart, aldosterone-mediated MR overactivation induces similar inflammatory, fibrotic, and oxidative stress responses, eventually leading to adverse outcomes such as heart failure, malignant arrhythmias, and myocardial infarction. Therefore,Mineralocorticoid receptor antagonists (MRAs), as diuretics, help regulate water and electrolyte balance and are used to treat conditions such as primary aldosteronism, hypertension, heart failure (HF), and chronic kidney disease (CKD). Currently, the most commonly used MRA in clinical practice is spironolactone, which belongs to the steroid class. Due to its low selectivity for MR, its concentration in the kidneys is six times higher than in the heart, resulting in a high incidence of hyperkalemia when administered. Eplerenone, a second-generation MRA, also has a steroid structure but exhibits higher selectivity for MR, stronger anti-aldosterone activity than spironolactone, and fewer side effects. The third generation MRA, represented by non-steroidal finerenone, shows high selectivity for MR and balanced distribution in both the heart and kidneys, making it less likely to cause hyperkalemia. Regarding Diabetic NephropathyDiabetic nephropathy is one of the most significant complications of diabetes and a principal cause of chronic kidney disease and ESRD. Approximately one-third of diabetic patients develop diabetic nephropathy, and if coupled with substantial proteinuria, it progresses to ESRD within roughly five years. According to the International Diabetes Federation (IDF) data from 2021, around 537 million adults (age 20-79) worldwide had diabetes, constituting one-tenth of the adult population, and this number is projected to increase to 783 million by 2045, accounting for 12.2%. According to a report by Kenneth Research, the global market size for diabetic nephropathy treatment drugs was $2.7 billion in 2018. By 2024, the compound annual growth rate (CAGR) is expected to be maintained at 5.9%, reaching a market value of $3.8 billion. How to obtain the latest research advancements in the field of biopharmaceuticals? In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. 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05 Aug 2024

·www.biospace.com

Bayer’s Finerenone Hits Primary Endpoint in Phase III Heart Failure Trial

Bayer’s global pharmaceuticals headquarters in Germany iStock/ Umut Tolga Pehlivan With the late-stage win, Bayer announced Monday that it plans to talk to regulators about seeking approval in an indication that is central to its $3 billion-plus peak sales forecast. Bayer said Monday its Phase III cardiovascular outcomes trial hit the primary endpoint, positioning the company to discuss with regulators filing for approval of finerenone in heart failure. The FDA approved finerenone in adults with chronic kidney disease associated with type 2 diabetes in 2021. Bayer, which sells the drug as Kerendia in the kidney indication, also identified the potential for the non-steroidal, selective mineralocorticoid receptor antagonist to improve outcomes in people with heart failure with mildly reduced or preserved ejection fraction. Bayer put that idea to the test in the FINEARTS-HF study. Investigators randomized around 6,000 people with symptomatic heart failure to take finerenone or placebo once a day for up to 42 months. Monday, Bayer said finerenone significantly reduced the composite of cardiovascular death and total heart failure events compared to placebo. The significant reduction caused the trial to hit its primary endpoint. Bayer is yet to share data from the study but is sufficiently encouraged by the results to outline plans to talk to regulatory agencies about filing for approval. Finerenone was well tolerated in the study, according to Bayer. While the company did not share data on safety and tolerability, the positive topline finding is encouraging for a molecule with a mechanism of action that has proven problematic in the past. Mineralocorticoid receptor antagonists such as spironolactone and eplerenone are used to treat heart failure with reduced ejection fraction. In that population, the drugs have improved outcomes in clinical trials. However, spironolactone was less impressive in a trial in heart failure with preserved ejection fraction, failing to reduce cardiovascular mortality while raising the risk of elevated potassium levels. Bayer’s trial program, which has enrolled more than 15,000 patients, and real-world finerenone use in kidney disease patients suggest the risk of elevated potassium levels may be lower for its molecule. The combination of improved cardiovascular outcomes and acceptable tolerability underpins Bayer’s hopes of turning finerenone into a blockbuster. The company is targeting peak sales of more than 3 billion euros ($3.3 billion). Bayer has retained the sales target even as Kerendia has made a slow start in kidney disease. Talking on an earnings call in May, Stefan Oelrich, head of Bayer’s pharmaceuticals unit, said “I think we’ve all been a little underwhelmed with the development of the renal market.” Oelrich said the market is “definitely not progressing at a speed that we had wished for” but predicted heart failure “will ultimately ... allow us to get to peak sales.” Finerenone is one of a clutch of key growth products at Bayer. The drugmaker shared positive Phase III data on another key product, prostate cancer drug Nubeqa, in July.

Phase 3Drug ApprovalClinical Result

100 Deals associated with Spironolactone

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KEGG	Wiki	ATC	Drug Bank
D00443	Spironolactone	C03DA01	DB00421

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Myocardial Infarction	United States	CMP Development LLC	04 Aug 2017
Stroke	United States	CMP Development LLC	04 Aug 2017
Nephrotic Syndrome	United States	Pfizer Inc.	30 Jun 1981
Ascites	United States	Pfizer Inc.	21 Jan 1960
Essential Hypertension	United States	Pfizer Inc.	21 Jan 1960
Liver Cirrhosis	United States	Pfizer Inc.	21 Jan 1960
Edema	-	Pfizer Inc.	01 Jan 1959
Heart Failure	-	Pfizer Inc.	01 Jan 1959
Hyperaldosteronism	-	Pfizer Inc.	01 Jan 1959
Hypertension	-	Pfizer Inc.	01 Jan 1959
Hypokalemia	-	Pfizer Inc.	01 Jan 1959

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Heart Failure	Discovery	India	CMP Pharma, Inc.	08 Mar 2019
Hypertension	Discovery	India	CMP Pharma, Inc.	06 Mar 2019
Edema	Discovery	India	CMP Pharma, Inc.	28 Feb 2019

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05010707 (TREAT, CTgov)	Phase 2	-	39	Hormone Profile+Spironolactone+Transdermal patch (Transdermal Estradiol Plus Spironolactone)	gnywwimopp(oqhzgtfisw) = tfdugmewic lgjydkmxyb (jrwfxrmxwl, yvihpsitgk - mizsxmtxse) View more	-	26 Nov 2024
				Hormone Profile+Spironolactone+Daily Sublingual Tablet (Daily Sublingual Estradiol Plus Spironolactone)	gnywwimopp(oqhzgtfisw) = miohcruxew lgjydkmxyb (jrwfxrmxwl, hvovoivtjf - rkrstacoda) View more
ESC2024	Not Applicable	Heart Failure \| Tachycardia, Ventricular Maintenance	405	Spironolactone	eavfralzlq(esrtklsccw): HR = 0.59, P-Value = 0.023	Positive	02 Sep 2024
				Eplerenone
NCT02169089 (MAGMA, Pubmed \| Circulation) Manual	Phase 4	Diabetes Mellitus, Type 2 \| Chronic Kidney Diseases	79	Spironolactone 25 mg	joadgwvgdb(vqcesdjilp) = bkykthdqdi uktkjlvvvl (fmlmaaqrhh, 10.0) View more	Positive	27 Aug 2024
				Placebo	joadgwvgdb(vqcesdjilp) = nyfnasudgj uktkjlvvvl (fmlmaaqrhh, 10.7) View more
ENDO2024	Not Applicable	Hypertension	-	Licorice Root Supplement	ddmoleikgd(uvubgtdzbd) = A tentative diagnosis of licorice-induced hyperaldosteronism was made and the patient was treated with a taper of spironolactone hcwwwfajce (zqorzainss ) View more	-	01 Jun 2024
				Hydrochlorothiazide
ENDO2024	Not Applicable	-	-	Cyproterone Acetate 12.5mg	bhbpoinjre(vckertbqac) = gsdmupimli duhaerrnsi (ivdoksntkq, 158.6) View more	-	01 Jun 2024
				Spironolactone 100mg	bhbpoinjre(vckertbqac) = ekumclroah duhaerrnsi (ivdoksntkq, 112.03) View more
NCT00094302 (TOPCAT, ESC2024)	Phase 3	Heart failure with normal ejection fraction serum creatinine	-	Spironolactone	sqpdiuzflh(leovlqyiyz) = gkzhkoshar idkwlmjlyq (stqboldrgo )	Positive	13 May 2024
				Placebo	sqpdiuzflh(leovlqyiyz) = tvoxavutmi idkwlmjlyq (stqboldrgo )
HOMAGE trial (ESC2024)	Not Applicable	matrix metallopeptidase-2 (MMP-2) \| insulin like growth factor binding protein-2 (IGFBP-2) \| N-terminal pro-b-type natriuretic peptide (NT-proBNP) ... View more	421	Spironolactone	oigxhdqdwh(tegvatmopg) = cynvabiqit xgoqblgjaj (xsbicldcwj )	Positive	11 May 2024
				Control	oigxhdqdwh(tegvatmopg) = mawqiwsmev xgoqblgjaj (xsbicldcwj )
NCT02556450 (HOMAGE, Pubmed) Manual	Phase 2	Heart Failure carboxyterminal propeptide of procollagen I (PICP) \| carboxyterminal telopeptide of collagen I (CITP)	290	Spironolactone 2Spironolactone	ctsbvadpje(rrlskwdrhq) = jmdevjxoof tzovkirafr (vrumcwtarh )	Positive	09 May 2024
				Usual therapy	ctsbvadpje(rrlskwdrhq) = alrcuscaub tzovkirafr (vrumcwtarh )
ESC2024	Not Applicable	Myocardial Ischemia \| Tachycardia, Ventricular	563	Eplerenone	ptxesmkawn(bfhohjikun): HR = 0.48, P-Value = 0.003	Positive	09 Apr 2024
				Spironolactone
ISRCTN12892056 (Pubmed \| BMJ Open)	Phase 3	Acne Vulgaris	-	Spironolactone 50 mg/day	oobeqzqasg(ropqictsro) = uiprjifpfx bgdfuiuhwc (ruwoythrrg )	-	01 Dec 2023

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