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Last update 24 Mar 2025

Digoxin

Last update 24 Mar 2025

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

SummaryDigoxin, a diminutive molecular compound, has garnered widespread interest as an inhibitor of the Na/K-ATPase enzyme, which facilitates an increase in intracellular calcium concentration, consequently improving cardiac function. Although primarily targeted for the treatment of heart failure, atrial fibrillation, and assorted cardiac arrhythmias, Digoxin's effectiveness and low-cost nature has garnered it significant acclaim since its first approval by GSK Plc in 1954, and continues to be prescribed frequently despite its age. However, caution must be exercised due to its slender therapeutic window and propensity for toxicity, necessitating frequent and thorough monitoring of patients taking Digoxin by their healthcare provider.

Drug Type

Small molecule drug

Synonyms

12β-hydroxydigitoxin, Digaoxin, Digoxin (JP17/USP)

+ [8]

Target

Na/K-ATPase

Action

inhibitors

Mechanism

Na/K-ATPase inhibitors(Sodium/potassium-transporting ATPase inhibitors)

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Arrhythmias, CardiacAcute congestive heart failureTachycardia+ [2]

Inactive Indication

Chemotherapy-induced nausea and vomitingDiabetes Mellitus, Type 2Epilepsy+ [2]

Originator Organization

GSK Plc

Active Organization

Hikma Pharmaceuticals International Ltd.

Shanghai Harvest Pharmaceutical Co., LtdTaiyo Pharma Co., Ltd.

+ [2]

Inactive Organization

Tesaro, Inc.

GSK Plc

Theracos, Inc.

+ [1]

Drug Highest PhaseApproved

First Approval Date

United States (16 Nov 1954),

Atrial FibrillationHeart Failure

Regulation-

Structure/Sequence

Molecular FormulaC41H64O14

InChIKeyLTMHDMANZUZIPE-PUGKRICDSA-N

CAS Registry20830-75-5

230

Clinical Trials associated with Digoxin

NCT06240403

/ Not yet recruitingPhase 2IIT

Digoxin: a New Senolytic to Repair Dysfunctional Adipose Tissue in Patients With Heart Failure and Type II Diabetes Mellitus

In pilot studies the investigators have shown that subcutaneous adipose tissue (SAT) from patients with reduced ejection fraction heart failure (HFrEF) and type 2 diabetes mellitus (T2DM) is dysfunctional. Endothelial cells from the adipose tissue from these patients are senescent and have deleterious effects on healthy human subcutaneous adipocytes, including increasing expression of IL-6 (gene and protein) and reducing glucose uptake. Digoxin, a well-established treatment for HFrEF, selectively clears these senescent endothelial cells and prevents adipocyte dysfunction. This study will examine the effect of digoxin on adipose tissue on the burden of senescent cells.

Start Date01 Sep 2025

Sponsor / Collaborator

University of Leeds

NCT06701812

/ Not yet recruitingPhase 2IIT

Evaluation of Digoxin for Relapsed Non-WNT, Non-SHH Medulloblastoma

The purpose of this study is to evaluate the efficacy of digoxin in treating relapsed non-SHH, non-WNT medulloblastoma in pediatric and young adult patients.

Start Date01 Mar 2025

Sponsor / Collaborator

H. Lee Moffitt Cancer Center & Research Institute, Inc.

NCT06813924

/ RecruitingPhase 1

An Open-Label, Fixed-Sequence Study to Evaluate the Effect of Etavopivat on the Single-Dose Pharmacokinetics of Midazolam, Digoxin, Rosuvastatin, Pitavastatin, and Metformin in Healthy Adult Participants

The study aims to test if a new medicine called etavopivat potentially affects other medicines in healthy participants. The purpose of the study is to investigate whether the use of etavopivat affects the breakdown and metabolism of commonly used medicines in the body. During the study, participants will receive etavopivat and five different medicines that are already approved and available on the market, and which can be prescribed by doctors. These marketed medicines are called substrate drugs and they are: digoxin, pitavastatin, metformin, midazolam, and rosuvastatin. During a period of the study, participants will take 2 tablets of etavopivat daily for 10 consecutive days. The study will last for about 34 to 64 days.

Start Date06 Feb 2025

Sponsor / Collaborator

Novo Nordisk A/S

100 Clinical Results associated with Digoxin

100 Translational Medicine associated with Digoxin

100 Patents (Medical) associated with Digoxin

18,107

Literatures (Medical) associated with Digoxin

31 Dec 2025·SCANDINAVIAN CARDIOVASCULAR JOURNAL

The use of antiarrhythmic drugs for atrial fibrillation in Finland 2007–2018

Article

Author: Marjamaa, Annukka ; Siponen, Rasmus ; Lehto, Mika ; Hartikainen, Juha ; Teppo, Konsta ; Putaala, Jukka ; Airaksinen, Juhani ; Aro, Aapo ; Mustonen, Pirjo ; Salmela, Birgitta ; Haukka, Jari ; Virrankorpi, Janne ; Linna, Miika ; Lappalainen, Antti ; Halminen, Olli

BACKGROUND:

Patients with atrial fibrillation (AF) are often treated with antiarrhythmic drugs (AADs) to maintain sinus rhythm and with heart rate-lowering drugs to achieve the optimal rate control. In this study, we investigated trends in the use of AADs and rate control drugs in Finnish patients with AF.

METHODS AND RESULTS:

The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study is a nationwide study including all patients with AF in Finland from 2007 to 2018. The number of AAD purchases and the proportions of all prevalent AF patients in a certain year of interest were calculated. In total, 391030 AF patients were identified between 2007 and 2018, and 39,816 (10.2%) of them had purchased either class I or III AADs. The proportion of patients using classes I and III AADs decreased from 8.6% to 6.3%. Flecainide and amiodarone were the most often used AADs. The use of flecainide and amiodarone decreased from 4.9% to 3.9% and 1.9% to 1.5%, respectively. The proportion of patients on beta-blockers remained stable at 75%. Dronedarone became available in 2011 when it also was the most used (0.8% of patients), but the use decreased thereafter. The use of sotalol and digoxin decreased from 1.5% to 0.6% and 24.6% to 11.0% over the study period.

CONCLUSION:

The number of AAD purchases increased alongside with the increasing prevalence of AF, whereas the proportion of AF patients on classes I and III AADs and digoxin decreased between 2007 and 2018. Flecainide remained the most used AAD followed by amiodarone.

01 May 2025·JOURNAL OF CLINICAL EPIDEMIOLOGY

Potential interactions between digoxin and direct oral anticoagulants: application of cohort & novel case-crossover designs

Article

Author: Smeeth, Liam ; Leyrat, Clémence ; Banerjee, Amitava ; Warren-Gash, Charlotte ; Bhaskaran, Krishnan ; Douglas, Ian J ; Wong, Angel Ys

OBJECTIVE:

Direct oral anticoagulants(DOACs) are commonly co-prescribed with digoxin, but whether there is a drug interaction between them is unclear. We aimed to investigate potential drug-interactions between DOACs and digoxin.

STUDY DESIGN AND SETTING:

We identified DOAC users during 1/1/2011-31/12/2019 using data from Clinical Practice Research Datalink Aurum in cohort design with propensity-score to compare the hazards of effectiveness cardiovascular and mortality outcomes and safety bleeding outcomes, respectively in DOAC+digoxin users versus DOAC+beta-blockers users. A case-crossover design was conducted to compare odds of exposure to different drug initiation patterns in hazard period versus referent period.

RESULTS:

Of 397,459 DOAC users, we identified 25,251 co-prescribed digoxin and 109,779 co-prescribed beta-blockers in cohort study. A lower proportion of DOAC+digoxin users were men (46%) in contrast with that of DOAC+beta-blocker users (53%). Mean age of DOAC+digoxin users(77.1years) were higher than DOAC+beta-blockers users(74.5years). No increased risk of pharmacologically predictable DOAC safety outcomes or specific effectiveness outcomes was seen with DOAC+digoxin. A higher risk of all-cause mortality (hazard ratio[HR]:1.35; 99% CI:1.14-1.61) was observed with DOAC+digoxin, versus DOAC+beta-blockers. In the case-crossover study, a 24% higher odds of all-cause mortality was seen with initiating digoxin while taking DOAC (odds ratio[OR]:1.24; 99%CI:1.06-1.45); and a 63% higher odds was also seen with initiating DOAC while taking digoxin (OR:1.63; 99%CI:1.41-1.88).

CONCLUSION:

We found no increased risk of bleeding when DOACs are used with digoxin, suggesting combined use does not lead to drug-drug interaction. Future work is recommended to investigate the underlying mechanism of association with all-cause mortality.

01 Apr 2025·Pharmacological Reports

Paracetamol, its metabolites, and their transfer between maternal circulation and fetal brain in mono- and combination therapies

Article

Author: Saunders, Norman R ; Huang, Yifan ; Habgood, Mark D ; Dziegielewska, Katarzyna M ; Qiu, Fiona

Abstract:

Background:

Due to its availability and perceived safety, paracetamol is recommended even during pregnancy and for neonates. It is used frequently alone or in combination with other drugs required for the treatment of various chronic conditions. The aim of this study was to investigate potential effects of drug interactions on paracetamol metabolism and its placental transfer and entry into the developing brain.

Methods:

Sprague Dawley rats at postnatal day P4, pregnant embryonic day E19 dams, and non-pregnant adult females were administered paracetamol (15 mg/kg) either as monotherapy or in combination with one of seven other drugs: cimetidine, digoxin, fluvoxamine, lamotrigine, lithium, olanzapine, valproate. Concentrations of parent paracetamol and its metabolites (paracetamol-glucuronide, paracetamol-glutathione, and paracetamol-sulfate) in plasma, cerebrospinal fluid (CSF) and brain were measured by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and their entry into the brain, CSF and transfer across the placenta were estimated.

Results:

In monotherapy, concentration of parent paracetamol in plasma, CSF, and brain remained similar and at all ages brain entry was unrestricted. In combination therapies, CSF entry of paracetamol increased following co-treatment with olanzapine. Placental transfer of parent paracetamol remained unchanged, however, transfer of paracetamol-sulfate increased with lamotrigine co-administration. Acutely administered paracetamol was more extensively metabolized in adults compared to younger ages resulting in increased concentration of its metabolites with age.

Conclusions:

Developmental changes in the apparent brain and CSF entry of paracetamol appear to be determined more by its metabolism, rather than by cellular control of its transfer across brain and placental barriers.

144

News (Medical) associated with Digoxin

27 Feb 2025

·www.prnewswire.com

Neurocrine Biosciences Reports Patient-Reported Outcome Data from KINECT-PRO™ Study for INGREZZA® (valbenazine) Capsules in Tardive Dyskinesia: Significant and Clinically Meaningful Improvements in Functionality and Quality of Life Measures

SAN DIEGO, Feb. 27, 2025 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced top-line data from a Phase 4 study, KINECT-PRO™, demonstrating clinically meaningful and sustained effects of INGREZZA® (valbenazine) capsules on the physical, social and emotional impacts experienced by patients living with tardive dyskinesia (TD), irrespective of TD severity or underlying psychiatric condition. KINECT-PRO is the first study to show patient-reported impact of a vesicular monoamine transporter 2 inhibitor, specifically INGREZZA, on TD using multiple clinically validated scales, including the Tardive Dyskinesia Impact Scale used to evaluate the physical, social and emotional impact of involuntary movements. These patient-reported outcome measures provide a more complete perspective on a patient's experience of living with TD and the broad range of improvements that occurred following treatment with INGREZZA. The results of KINECT-PRO will be shared at upcoming scientific conferences. "Tardive dyskinesia can significantly impact many aspects of patients' lives, including daily activities, work or school attendance and social interactions," said Eiry W. Roberts, M.D., Chief Medical Officer, Neurocrine Biosciences. "The data from the KINECT-PRO trial, which was designed to follow typical clinical practice, show that patients and clinicians observed substantial reduction in the impact and severity of TD, as well as improvement in overall quality of life with use of INGREZZA. Importantly, patients reported significant improvements across measures regardless of their underlying psychiatric conditions or the baseline severity of their TD involuntary movement symptoms." Fifty-nine patients were enrolled in the KINECT-PRO study and received once-daily INGREZZA (40 mg, 60 mg or 80 mg) for up to 24 weeks. Fifty-two patients completed the Week 24 visit. There were comparable numbers of patients across TD severity (mild vs. moderate/severe) and underlying psychiatric condition subgroups (schizophrenia or schizoaffective disorder vs. bipolar disorder or major depression). The primary objective of the KINECT-PRO study was to evaluate changes in patient-reported physical and socio-emotional impacts of TD, changes in a person's work, family, social life and overall sense of health and well-being during INGREZZA treatment. These outcomes were measured at Weeks 4, 8, 16 and 24 by the Tardive Dyskinesia Impact Scale (TDIS), the Sheehan Disability Scale (SDS) and the EQ Visual Analogue Scale (EQ-VAS), respectively. The secondary objective was to evaluate clinician- and patient-reported changes in TD severity as measured by the Abnormal Involuntary Movement Scale (AIMS), the Patient Global Impression of Change–TD (PGI-C) and Clinical Global Impression of Severity–TD (CGI-TD-S). Results showed significant and sustained improvements from baseline in all three patient-reported outcome measures, including patients with either mild or moderate/severe TD, with improvements observed as early as four weeks at the lowest dose (40 mg). AIMS scores also showed sustained reductions in involuntary movements, regardless of TD severity or underlying psychiatric condition. In the study, safety and tolerability of treatment was consistent with the known profile of INGREZZA, with no new concerns identified. About the KINECT-PRO™ Phase 4 Study The KINECT-PRO™ Phase 4, open-label study was designed to evaluate patient reported outcomes on the use of INGREZZA® (valbenazine) capsules in a tardive dyskinesia (TD) patient population reflective of real-world clinical practice. Participants had at least mild TD, were aware of and experiencing at least mild distress from their abnormal, involuntary movements and had a clinical diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder or major depression. The KINECT-PRO study included a four-week screening period, a 24-week treatment period during which participants received 40 mg of INGREZZA once-daily for the first four weeks, followed by flexible dosing of 40 mg, 60 mg or 80 mg once-daily based on individual treatment needs and a two-week safety follow-up period. Baseline socio-demographic and clinical characteristics of the participants were broadly similar to those of the KINECT®-3 and KINECT®-4 studies. About the Tardive Dyskinesia Impact Scale (TDIS) The Tardive Dyskinesia Impact Scale (TDIS) is a novel, psychometrically validated patient-reported outcome measure in TD. It was developed by Neurocrine Biosciences from qualitative studies and Phase 3 trials of INGREZZA for the treatment of TD (KINECT®-3 and KINECT®-4) as a comprehensive measure of impact and burden of TD from a patient's perspective. The TDIS consists of 11 questions evaluating physical and socio-emotional impact. Six domains are assessed: mouth/throat, dexterity, mobility, pain, social and emotional. The TDIS allows people with TD to rate how their symptoms affect daily activities and how their uncontrollable movements make them feel. The questionnaire captures relevant information about the impact of TD to provide a more holistic assessment of the condition. Validation of this scale was published in the Journal of Patient-Reported Outcomes. About Tardive Dyskinesia (TD) Tardive dyskinesia (TD) is a movement disorder that is characterized by uncontrollable, abnormal and repetitive movements of the face, torso and/or other body parts, which may be disruptive and negatively impact patients. The condition is associated with taking certain kinds of mental health medicines (antipsychotics) that help control dopamine receptors in the brain. Taking antipsychotics commonly prescribed to treat mental illnesses such as major depressive disorder, bipolar disorder, schizophrenia and schizoaffective disorder and other prescription medicines (metoclopramide and prochlorperazine) used to treat gastrointestinal disorders are associated with TD. In patients with TD, these treatments are thought to result in irregular dopamine signaling in a region of the brain that controls movement. The symptoms of TD can be severe and are often persistent and irreversible. TD is estimated to affect at least 800,000 adults in the U.S. About INGREZZA® (valbenazine) Capsules and INGREZZA® SPRINKLE (valbenazine) Capsules INGREZZA is a selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved by the U.S. Food and Drug Administration for the treatment of adults with tardive dyskinesia and the treatment of chorea associated with Huntington's disease (HD). Only INGREZZA offers a therapeutic dose from day one with no required titration. INGREZZA, developed by Neurocrine Biosciences, selectively inhibits VMAT2 with no appreciable binding affinity for VMAT1, dopaminergic (including D2), serotonergic, adrenergic, histaminergic or muscarinic receptors. While the specific way INGREZZA works to treat TD and HD chorea is not fully understood, INGREZZA is unique in that it selectively and specifically targets VMAT2 to inhibit the release of dopamine, a chemical in the brain that helps control movement. INGREZZA is believed to reduce extra dopamine signaling, which may lead to fewer uncontrollable movements. INGREZZA is always one capsule, once daily and can be taken together with most stable mental health regimens such as antipsychotics or antidepressants. Only INGREZZA offers the benefit of a sprinkle formulation, INGREZZA® SPRINKLE, for those who experience dysphagia, have difficulty swallowing or prefer not to swallow a pill. INGREZZA and INGREZZA SPRINKLE dosages approved for use are 40 mg, 60 mg and 80 mg capsules. Important Information Approved Uses INGREZZA® (valbenazine) capsules or INGREZZA® SPRINKLE (valbenazine) capsules are prescription medicines used to treat adults with: movements in the face, tongue, or other body parts that cannot be controlled (tardive dyskinesia). involuntary movements (chorea) of Huntington's disease. INGREZZA or INGREZZA SPRINKLE do not cure the cause of involuntary movements, and do not treat other symptoms of Huntington's disease, such as problems with thinking or emotions. It is not known if INGREZZA or INGREZZA SPRINKLE is safe and effective in children. IMPORTANT SAFETY INFORMATION INGREZZA or INGREZZA SPRINKLE can cause serious side effects in people with Huntington's disease, including: depression, suicidal thoughts, or suicidal actions. Tell your healthcare provider before you start taking INGREZZA or INGREZZA SPRINKLE if you have Huntington's disease and are depressed (have untreated depression or depression that is not well controlled by medicine) or have suicidal thoughts. Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is especially important when INGREZZA or INGREZZA SPRINKLE is started and when the dose is changed. Call your healthcare provider right away if you become depressed, have unusual changes in mood or behavior, or have thoughts of hurting yourself. Do not take INGREZZA or INGREZZA SPRINKLE if you: are allergic to valbenazine, or any of the ingredients in INGREZZA or INGREZZA SPRINKLE. INGREZZA or INGREZZA SPRINKLE can cause serious side effects, including: Allergic reactions. Allergic reactions, including an allergic reaction that causes sudden swelling called angioedema can happen after taking the first dose or after many doses of INGREZZA or INGREZZA SPRINKLE. Signs and symptoms of allergic reactions and angioedema include: trouble breathing or shortness of breath, swelling of your face, lips, eyelids, tongue, or throat, or other areas of your skin, trouble with swallowing, or rash, including raised, itchy red areas on your skin (hives). Swelling in the throat can be life-threatening and can lead to death. Stop taking INGREZZA or INGREZZA SPRINKLE and go to the nearest emergency room right away if you develop these signs and symptoms of allergic reactions and angioedema. Sleepiness and tiredness that could cause slow reaction times (somnolence and sedation). Do not drive a car or operate dangerous machinery until you know how INGREZZA or INGREZZA SPRINKLE affects you. Drinking alcohol and taking other medicines may also cause sleepiness during treatment with INGREZZA or INGREZZA SPRINKLE. Heart rhythm problems (QT prolongation). INGREZZA or INGREZZA SPRINKLE may cause a heart rhythm problem known as QT prolongation. You have a higher chance of getting QT prolongation if you also take certain other medicines during treatment with INGREZZA or INGREZZA SPRINKLE. Tell your healthcare provider right away if you develop any signs or symptoms of QT prolongation, including: fast, slow, or irregular heartbeat (heart palpitations), shortness of breath, dizziness or lightheadedness, or fainting or feeling like you are going to faint. Neuroleptic Malignant Syndrome (NMS). NMS is a serious condition that can lead to death. Call a healthcare provider right away or go to the nearest emergency room if you develop these symptoms and they do not have another obvious cause: high fever, stiff muscles, problems thinking, irregular pulse or blood pressure, increased sweating, or very fast or uneven heartbeat. Parkinson-like symptoms. Symptoms include: body stiffness, drooling, trouble moving or walking, trouble keeping your balance, shaking (tremors), or falls. Before taking INGREZZA or INGREZZA SPRINKLE, tell your healthcare provider about all of your medical conditions including if you: have liver or heart problems, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Make sure you tell all of your healthcare providers that you are taking INGREZZA or INGREZZA SPRINKLE. Taking INGREZZA or INGREZZA SPRINKLE with certain other medicines may cause serious side effects. Especially tell your healthcare provider if you: take digoxin or take or have taken a monoamine oxidase inhibitor (MAOI) medicine. You should not take INGREZZA or INGREZZA SPRINKLE if you are taking, or have stopped taking, a MAOI within the last 14 days. The most common side effects of INGREZZA or INGREZZA SPRINKLE in people with tardive dyskinesia are sleepiness and tiredness. The most common side effects of INGREZZA or INGREZZA SPRINKLE in people with chorea associated with Huntington's disease include sleepiness and tiredness, raised itchy red areas on your skin (hives), rash, and trouble getting to sleep or staying asleep. These are not all of the possible side effects of INGREZZA or INGREZZA SPRINKLE. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at or call 1-800-FDA-1088. Dosage Forms and Strengths: INGREZZA and INGREZZA SPRINKLE are available in 40 mg, 60 mg, and 80 mg capsules. Please see full Prescribing Information, including Boxed Warning, and Medication Guide. About Neurocrine Biosciences, Inc. Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine and neuropsychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, classic congenital adrenal hyperplasia, endometriosis* and uterine fibroids*, as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders, because you deserve brave science. For more information, visit LinkedIn, X and Facebook. (*in collaboration with AbbVie) The NEUROCRINE BIOSCIENCES Logo, NEUROCRINE, YOU DESERVE BRAVE SCIENCE, KINECT and INGREZZA are registered trademarks of Neurocrine Biosciences, Inc. Forward-Looking Statements In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. These statements include, but are not limited to, statements regarding the potential benefits to be derived from INGREZZA and the value INGREZZA may bring to patients. Factors that could cause actual results to differ materially from those stated or implied in the forward-looking statements include, but are not limited to, the following: risks and uncertainties associated with Neurocrine Biosciences' business and finances in general, as well as risks and uncertainties associated with the commercialization of INGREZZA; whether INGREZZA receives adequate reimbursement from third-party payors; risks and uncertainties relating to competitive products and technological changes that may limit demand for INGREZZA; risks associated with the Company's dependence on third parties for development and manufacturing activities related to INGREZZA, and the ability of the Company to manage these third parties; risks that additional regulatory submissions for INGREZZA or other product candidates may not occur or be submitted in a timely manner; risks that the FDA or other regulatory authorities may make adverse decisions regarding INGREZZA; risks that post-approval INGREZZA commitments or requirements may be delayed; risks that INGREZZA may be precluded from commercialization by the proprietary or regulatory rights of third parties, or have unintended side effects, adverse reactions or incidents of misuse; and other risks described in the Company's periodic reports filed with the Securities and Exchange Commission, including without limitation the Company's annual report on Form 10-K for the year ended December 31, 2024. Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof other than required by law. © 2025 Neurocrine Biosciences, Inc. All Rights Reserved. CAP-VBZ-US-0047 02/2025 SOURCE Neurocrine Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultPhase 3Drug ApprovalPhase 2

24 Jan 2025

·www.prnewswire.com

Clinical trial published in Nature Medicine shows proof of concept of PAGE's Therapeutics approach

BASEL, Switzerland, Jan. 24, 2025 /PRNewswire/ -- PAGE Therapeutics, a biotech company focused on tackling metastatic cancer spread at its root, is pleased to announce the publication of the results of a clinical study conducted by Prof. Nicola Aceto's team at ETH Zurich in collaboration with University Hospitals in Zurich, Liestal and Basel, Switzerland. The study design comprised measuring the effect of the cardiotonic agent digoxin (a widely used Na+/K+ ATPase inhibitor) in reducing the size of circulating tumor cells clusters, i.e. aggregates of tumor cells that travel in the bloodstream. The presence of CTC clusters in patients' blood is associated with poor prognosis, and preclinical studies conducted by Prof Aceto and other groups have shown how CTCs have much higher potential to seed metastases when travelling as clusters rather than when traveling as single cells. Furthermore, in preclinical cancer models, treatment with Na+/K+ ATPase inhibitors enables the reduction of CTC clusters and metastases, opening up a new potential cancer treatment paradigm based on which PAGE Therapeutics was founded. The present clinical study, published in the top-tier scientific journal Nature Medicine (link), has shown for the first time that the same effect on clusters can be achieved in humans. A cohort of 9 metastatic breast cancer patients were treated with digoxin for one week and evaluated against a control group. The primary endpoint – a reduction in size of CTC clusters – was met, with a statistically significant average reduction of 2.2 cells per cluster. The study has previously been listed by Nature Medicine as one of the 11 clinical trials that could shape medicine in 2023. PAGE Therapeutics owns an exclusive license on the use of digoxin and other existing Na+/K+ ATPase inhibitors in the prevention or treatment of metastasis, and, moreover, is developing new proprietary compounds purposely designed to maximize the dissolution of CTC clusters, which are showing much higher activity compared to digoxin in preclinical models. "This trial is a remarkable proof-of-mechanism for the use of Na+/K+ ATPase inhibitors to disrupt CTC clusters in breast cancer," said Prof. Aceto, principal investigator of the study and co-founder of PAGE Therapeutics. "We administered a low digoxin dose for just one week, and yet we have seen a statistically significant result. With PAGE Therapeutics' new compounds, we are already able to dissolve clusters and block the formation of metastases in preclinical models far more efficiently than with digoxin, and with these results we are confident that we can translate these effects in humans. We are extremely excited to bring forward the development of this potentially game changing approach." About Page PAGE Therapeutics AG (' Page') is a Swiss preclinical-stage biotech company spun out of the ETHZ and founded on the groundbreaking science of Prof. Nicola Aceto. Page targets the vulnerabilities of tumor cells circulating in the bloodstream and is developing novel therapies that can disrupt their clusters, inhibiting their ability to form metastases. Contact: [email protected] Logo: SOURCE PAGE Therapeutics AG WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

License out/inClinical Study

22 Jan 2025

·www.rigel.com

Rigel's Fostamatinib Being Studied by National Institute of Health in Patients with Sickle Cell Disease

First patient enrolled in NIH/NHLBI-sponsored Phase 1 Study of fostamatinib, Rigel's oral SYK inhibitor SOUTH SAN FRANCISCO, Calif., Jan. 22, 2025 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today announced the first patient has been enrolled in a Phase 1 study evaluating the safety and tolerability of escalating doses of fostamatinib, the company's oral spleen tyrosine kinase (SYK) inhibitor, in patients with sickle cell disease (SCD). The study is being sponsored by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institute of Health (NIH). Fostamatinib, marketed in the U.S. as TAVALISSE® (fostamatinib disodium hexahydrate) tablets, is approved for the treatment of adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. "Our Phase 1 study evaluating fostamatinib in patients with sickle cell disease is an opportunity to explore a potential new treatment option for a disease that is associated with a high degree of recurrent acute pain events and other acute and chronic potentially life-threatening complications," stated Richard Childs, M.D., scientific director of the NHLBI. "Preclinical research conducted by NIH/NHLBI investigators lead us to believe that SYK inhibition may have the potential to reduce complications related to red cell sickling and thrombo-inflammation in this patient population." "We are excited to support another important study conducted by the NIH/NHLBI for fostamatinib, as they investigate SYK inhibition and its potential to benefit patients with sickle cell disease, a devasting, lifelong condition," said Raul Rodriguez, Rigel's president and CEO. "The study focuses on an area of critical unmet need and contributes to Rigel's mission to improve the lives of patients with hematologic disorders and cancer." This open label Phase 1 dose-escalation study is expected to enroll approximately 20 patients with SCD (NCT05904093). The trial is led by principal investigator Swee Lay Thein, M.D., senior investigator and chief of the Sickle Cell Branch at the NHLBI. Patients will receive oral fostamatinib at a dose of 100 mg twice daily for 14 days, which will be escalated to 150 mg twice daily for an additional 28 days if tolerated. The primary objective of the study is to evaluate the safety and tolerability of fostamatinib. The secondary and exploratory objectives are to assess the mechanism of action of fostamatinib in SCD and mechanistic effects of fostamatinib mediated SYK inhibition on red blood cell membrane integrity and deformability, rate of sickling kinetics, platelet activation and aggregation, and neutrophil activation and neutrophil extracellular trap (NET) formation. The clinical study is being conducted at the NIH Clinical Center in Bethesda, Maryland and is being funded and sponsored by the NIH/NHLBI, with study material provided by Rigel. About SCD & SYK Inhibition Sickle cell disease (SCD) is a genetic hemoglobinopathy that leads to the production of abnormal hemoglobin, the protein that carries oxygen through the body. Normally, red blood cells are disc-shaped and flexible enough to move easily through the blood vessels. In sickle cell disease, red blood cells become rigid and crescent – or "sickle" – shaped, leading to strokes, infections, vaso-occlusive crises (VOC), and multi-organ dysfunction. The condition affects more than 100,000 people in the United States1 and an estimated 7-8 million people worldwide.2 In preclinical studies, R406, the active metabolite of fostamatinib, was shown to inhibit production of neutrophil extracellular traps (NETs) by neutrophils in vitro.3 In a humanized SCD mouse model, R406 treatment significantly decreased platelet ATP secretion and aggregation in response to collagen without a significant effect on bleeding time.4 Fostamatinib could potentially ameliorate SCD-related prothrombic state without an increase in bleeding, addressing an important unmet need. Furthermore, tyrosine phosphorylation of red blood cell (RBC) Band 3 (the anion exchanger 1, of the SLC4A1 gene) compromises the RBC's integrity, leading to shedding of red cell derived microparticles and release of hemoglobin and mitochondrial DNA, key contributors to thrombo-inflammation pathophysiology. By impacting phosphorylation of RBC Band 3 protein, fostamatinib offers the potential for enhanced RBC membrane stability and reduced sickling of RBCs.5 About TAVALISSE® Indication TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. Important Safety Information Warnings and Precautions Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required. Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to ≥3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation. Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE. Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation. TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose. Drug Interactions Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose. It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406. Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug. Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug. Adverse Reactions Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%). Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia. Please see www.TAVALISSEUSPI.com for Full Prescribing Information. To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088). TAVALISSE is a registered trademark of Rigel Pharmaceuticals, Inc. Disclaimer The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. About Rigel Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology company dedicated to discovering, developing and providing novel therapies that significantly improve the lives of patients with hematologic disorders and cancer. Founded in 1996, Rigel is based in South San Francisco, California. For more information on Rigel, the Company's marketed products and pipeline of potential products, visit www.rigel.com. Forward Looking Statements This press release contains forward-looking statements relating to, among other things, evaluating fostamatinib in patients with sickle cell disease and the potential of SYK inhibition to reduce complications related to red cell sickling and thrombo-inflammation. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements can be identified by words such as "explore", "potential", "may", "expected", "will" and similar expressions in reference to future periods. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Rigel's current beliefs, expectations, and assumptions and hence they inherently involve significant risks, uncertainties and changes in circumstances that are difficult to predict and many of which are outside of our control. Therefore, you should not rely on any of these forward-looking statements. Actual results and the timing of events could differ materially from those anticipated in such forward looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the development and commercialization of fostamatinib; risks that the FDA, European Medicines Agency, PMDA or other regulatory authorities may make adverse decisions regarding fostamatinib; risks that clinical trials may not be predictive of real-world results or of results in subsequent clinical trials; risks that fostamatinib may have unintended side effects, adverse reactions or incidents of misuses; the availability of resources to develop Rigel's product candidates; market competition; as well as other risks detailed from time to time in Rigel's reports filed with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2023 and subsequent filings. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. Rigel does not undertake any obligation to update forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise, and expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein, except as required by law. Contact for Investors & Media: Investors: Rigel Pharmaceuticals, Inc. 650.624.1232 ir@rigel.com Media: David Rosen Argot Partners 646.461.6387 david.rosen@argotpartners.com View original content to download multimedia:https://www.prnewswire.com/news-releases/rigels-fostamatinib-being-studied-by-national-institute-of-health-in-patients-with-sickle-cell-disease-302356919.html SOURCE Rigel Pharmaceuticals, Inc.

Drug ApprovalPhase 1Clinical ResultImmunotherapy

100 Deals associated with Digoxin

External Link

KEGG	Wiki	ATC	Drug Bank
D00298	Digoxin	C01AA05	DB00390

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Arrhythmias, Cardiac	China	Shanghai Harvest Pharmaceutical Co., Ltd	01 Jan 1995
Acute congestive heart failure	Japan	Taiyo Pharma Co., Ltd.	10 Sep 1957
Tachycardia	Japan	Taiyo Pharma Co., Ltd.	10 Sep 1957
Atrial Fibrillation	United States	Covis Pharma Holdings BV	16 Nov 1954
Heart Failure	United States	Covis Pharma Holdings BV	16 Nov 1954

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Phase 1	United States	ViiV Healthcare Ltd.	16 Dec 2020
Chemotherapy-induced nausea and vomiting	Phase 1	United States	Tesaro, Inc.	01 May 2015
Epilepsy	Phase 1	United States	GSK Plc	16 Jan 2012
Diabetes Mellitus, Type 2	Phase 1	United States	GSK Plc	11 Jun 2010
Metastatic human epidermal growth factor 2 positive carcinoma of breast	Phase 1	United States	GSK Plc	23 Apr 2008
Metastatic human epidermal growth factor 2 positive carcinoma of breast	Phase 1	Canada	GSK Plc	23 Apr 2008
Metastatic human epidermal growth factor 2 positive carcinoma of breast	Phase 1	South Korea	GSK Plc	23 Apr 2008

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03928210 (Nature) Manual	Early Phase 1	Metastatic breast cancer	9	Digoxin	rfdpunnoqp(xubwijknhi) = bkogxjlgpf swgllbfbkm (lqmliynpkn ) View more	Positive	24 Jan 2025
NCT05540600 (DIGOBET-AF, Pubmed \| Am J Cardiovasc Drugs)	Phase 3	Atrial Fibrillation	60	Digoxin 0.25 mg	grsyudsent(gnypvlkart) = fxjrotfhxm vgtuwqzbch (cdlekiddbp, 3.2)	Positive	26 Dec 2024
				Bisoprolol 5-10 mg	grsyudsent(gnypvlkart) = jqgdpcxngc vgtuwqzbch (cdlekiddbp, 3.4)
NCT04834557 (Pubmed \| Front Pharmacol)	Phase 2	Rheumatoid Arthritis IL-17A \| IL-23 \| HIF-1α ... View more	60	Digoxin 0.25 mg every other day	rfweqxrzjg(znousmvpsz) = fwmewszdjp fpacwfkfbl (rosabcqjkw )	Positive	21 Oct 2024
				Placebo	rfweqxrzjg(znousmvpsz) = wtxdoxtzce fpacwfkfbl (rosabcqjkw )
ESC2024	Not Applicable	Atrial Fibrillation	-	Intravenous Digoxin Loading Dose	grsfvttcyx(nbpxkhnxin) = mipxoneatb ggtcatwian (pknsgdcboh, 0.9 - 1.7) View more	-	30 Aug 2024
ESC2024	Not Applicable	Chronic heart failure \| Atrial Fibrillation	-	Digoxin	ihgfhmfuit(qjdhjqggnb) = vcjsgytuyi ujrgfzawad (zavckzbjsh, 17.2)	-	30 Aug 2024
NCT03559868 (CTgov)	Phase 1	Inflammation	45	digoxin (Digoxin 3 mcg/Kg/Day)	apnwawiuuf(qisyyhuadk) = zuunpczdxw xudqkvrytu (wuajousomn, 237) View more	-	12 Jul 2024
				digoxin (Digoxin 0.15 mcg)	apnwawiuuf(qisyyhuadk) = poyxtldzga xudqkvrytu (wuajousomn, 483) View more
ESC2023	Not Applicable	-	-	Digoxin	vbapfjgoyp(lrfyfdndzp) = jucciztcgz qpvludebtx (gvdnjtppsu ) View more	-	21 May 2023
NCT03909529 (CTgov)	Phase 1	Medication interactions	28	Carospir+digoxin (Drug-Drug Interaction Study)	abvecfomqy(jyxjxsbgup) = vmhcqztlrp ybngvnpbks (rptxfqiksw, 502.810) View more	-	01 May 2023
				Digoxin (LANOXIN) (Treatment-A- Single Dose of Digoxin (LANOXIN))	yyssxgajtb(dgvixcoocw) = pwmsulhudv zwsmuxiqyv (awxpgcerxq, uhpwigkvbr - whwnrmiuah) View more
NCT02391337 (RATE-AF, ESC 12022 \| ESC 22022) Manual	Phase 4	Heart failure with normal ejection fraction \| Atrial Fibrillation	130	Diazepam	fvlluurals(okazaxyzxn): AMD = 1.1 (95% CI, 1.0 - 1.2), P-Value = 0.003 View more	Positive	29 Aug 2022
				beta-blockers
NCT04425902 (CTgov)	Phase 1	HIV Infections	20	pravastatin+metoprolol+omeprazole+midazolam+montelukast+digoxin+caffeine+flurbiprofen (Treatment A: Probe Substrates)	wgkpouhuch(yteaxuryru) = lbjtymzfnv fdfthcuvim (ibkcxockkh, 31.1) View more	-	23 May 2022
				GSK3640254 (Treatment C: Probe Substrates + GSK3640254 200 mg)	wgkpouhuch(yteaxuryru) = odcnocquhx fdfthcuvim (ibkcxockkh, 32.4) View more

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