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Journal articles on the topic 'Sparsentan'

Author: Grafiati
Published: 7 June 2025
Last updated: 2 August 2025

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1

Dalal, Deepak. "Sparsentan a New Dual Endothelin Angiotensin Receptor Antagonist: Synpharyngitic Glomerulonephritis." Clinical Case Reports and Studies 3, no. 4 (2023): 1–5. http://dx.doi.org/10.59657/2837-2565.brs.23.074.

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Sparsentan a newly approved Dual Endothelin Angiotensin Receptor Antagonist for IgA nephropathy and glomerulosclerosis. Sparsentan drug known for its dual-action and high selectivity as it has the ability to target both Endothelin A receptor (ETAR) as well as Angiotensin II subtype 1 receptor (AT1R). According to EPPIK study (Phase-II), sparsentan's potential and safety for long-term Nephroprotection and Antiproteinuria in children with focal segmental glomerulosclerosis, IgA nephropathy, Alport syndrome will examined. IgA nephropathy, also known as synpharyngitic glomerulonephritis and Berger
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2

Dalal, Deepak, and Ravi Kant. "Sparsentan: A New Dual Endothelin Angiotensin Receptor Antagonist-Synpharyngitic Glomerulonephrities." Annals of Medical and Health Sciences Research 14, no. 4 (2024): 4. https://doi.org/10.5281/zenodo.14288332.

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Sparsentan is a newly approved Dual Endothelin Angiotensin Receptor Antagonist for glomerulosclerosis and IgA nephropathy. Sparsentan is dual-acting, highly selective antagonist has as its targets both the Endothelin A Receptor (ETAR) and the Angiotensin II Subtype 1 Receptor (AT1R). In the Phase 2 EPPIK study, sparsentan's potential and safety for long-term Nephroprotection and Antiproteinuria in children with focal segmental glomerulosclerosis, Minimal Change Disease (MCD), IgA nephropathy, IgAV, and Alport Syndrome (AS) will be examined. IgA nephropathy, also known as Berger's disease (vari
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3

Trachtman, Howard, Peter Nelson, Sharon Adler, et al. "DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGS." Journal of the American Society of Nephrology 29, no. 11 (2018): 2745–54. http://dx.doi.org/10.1681/asn.2018010091.

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BackgroundWe evaluated and compared the effects of sparsentan, a dual endothelin type A (ETA) and angiotensin II type 1 receptor antagonist, with those of the angiotensin II type 1 receptor antagonist irbesartan in patients with primary FSGS.MethodsIn this phase 2, randomized, double-blind, active-control Efficacy and Safety of Sparsentan (RE-021), a Dual Endothelin Receptor and Angiotensin Receptor Blocker, in Patients with Focal Segmental Glomerulosclerosis (FSGS): A Randomized, Double-blind, Active-Control, Dose-Escalation Study (DUET), patients aged 8–75 years with biopsy-proven FSGS, eGFR
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4

Chuang, Tzu-Hsien, Hsin-Yen Cho, and Sheng-Nan Wu. "The Evidence for Sparsentan-Mediated Inhibition of INa and IK(erg): Possibly Unlinked to Its Antagonism of Angiotensin II or Endothelin Type a Receptor." Biomedicines 10, no. 1 (2021): 86. http://dx.doi.org/10.3390/biomedicines10010086.

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Sparsentan is viewed as a dual antagonist of endothelin type A (ETA) receptor and angiotensin II (AngII) receptor and it could be beneficial in patients with focal segmental glomerulosclerosis. Moreover, it could improve glomerular filtration rate and augment protective tissue remodeling in mouse models of focal segmental glomerulosclerosis. The ionic mechanisms through which it interacts with the magnitude and/or gating kinetics of ionic currents in excitable cells were not thoroughly investigated. Herein, we aimed to examine the effects of varying sparsentan concentrations on ionic currents
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5

Kohan, Donald E., Patricia W. Bedard, Celia Jenkinson, Bruce Hendry, and Radko Komers. "Mechanism of protective actions of sparsentan in the kidney: lessons from studies in models of chronic kidney disease." Clinical Science 138, no. 11 (2024): 645–62. http://dx.doi.org/10.1042/cs20240249.

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Abstract Simultaneous inhibition of angiotensin II AT1 and endothelin ETA receptors has emerged as a promising approach for treatment of chronic progressive kidney disease. This therapeutic approach has been advanced by the introduction of sparsentan, the first dual AT1 and ETA receptor antagonist. Sparsentan is a single molecule with high affinity for both receptors. It is US Food and Drug Administration approved for immunoglobulin A nephropathy (IgAN) and is currently being developed as a treatment for rare kidney diseases, such as focal segmental glomerulosclerosis. Clinical studies have de
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6

P. Siva Krishna, M. M. Eswarudu, P. Srinivasa Babu, et al. "VALIDATED STABILITY INDICATING RP-HPLC METHOD FOR QUANTIFICATION OF SPARSENTAN IN PHARMACEUTICAL DOSAGE FORM: A 2023 USFDAAPPROVED DRUG." Rasayan J. Chem 17, no. 02 (2024): 631–41. http://dx.doi.org/10.31788/rjc.2024.1728805.

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The quantitative analysis of Sparsentan in the pharmaceutical dosage form has been accomplished through the development and validation of a simple rapid, precise, and sensitive reverse-phase high-performance liquid chromatography (RP-HPLC) method. Using a Zorbax SB 18 (150 x 4.6 mm, 3.5 µm) column and a mobile phase containing acetonitrile and potassium dihydrogen phosphate pH-3.0 adjusted with diluted orthophosphoric acid in a ratio of 40:60% v/v, Sparsentan was separated chromatographically using a Waters Alliance-e2695. The flow rate was 1.0 mL/min, and a photodiode array detector (PDA) ope
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7

Lerma, Edgar V. "A Closer Look at Sparsentan." Kidney News 17, no. 1 (2025): 16–17. https://doi.org/10.62716/kn.000422024.

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8

Kraus, Dagmar. "IgA-Nephropathie: erste Daten zu Sparsentan." Uro-News 27, no. 7-8 (2023): 38–39. http://dx.doi.org/10.1007/s00092-023-5754-3.

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9

Groothof, Dion, Reinold O. B. Gans, and Stephan J. L. Bakker. "Sparsentan and kidney protection: improved medullary oxygenation?" Lancet 404, no. 10465 (2024): 1808. http://dx.doi.org/10.1016/s0140-6736(24)01168-1.

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10

Iida, Yoshihito, Guihua Gao, Chadia Beaini, Ali Ghanem, Sandeep Varma, and Magdy Elsharkawy. "Efficacy of Antihypertensive Therapy in Primary IgA Nephropathy in Adults: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials." Journal of Clinical Question 2, no. 2 (2025): e69. https://doi.org/10.69854/jcq.2025.0010.

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Background: IgA nephropathy (IgAN) is a leading cause of chronic kidney disease, with proteinuria and hypertension accelerating the disease’s progression. While the renin-angiotensin-aldosterone system inhibitors remain the standard treatment, emerging therapies such as endothelin receptor antagonists (ERAs) offer potential renoprotective benefits. This study conducted a network meta-analysis (NMA) of randomized controlled trials (RCTs) to compare the efficacy of various antihypertensive agents in reducing proteinuria and preserving kidney function in adults with IgAN. Methods: A comprehensive
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11

Hendry, Bruce M., Donald E. Kohan, Rob Geletka, Celia P. Jenkinson, Charles Chen, and Patricia W. Bedard. "Sparsentan Receptor Occupancy Modeling, Clinical Actions, and Safety." Journal of the American Society of Nephrology 34, no. 11S (2023): 799. http://dx.doi.org/10.1681/asn.20233411s1799a.

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12

Gupta, Ratan Das, and Mesbah Uddin Noman. "Sparsentan: Sparsentan- A novel, non- immunosuppressive, dual action angiotensin II and endothelin A receptor antagonist -A new hope for glomerular disease." Journal of Shaheed Suhrawardy Medical College 14, no. 2 (2024): 58–62. http://dx.doi.org/10.3329/jssmc.v14i2.73180.

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13

Hunter‐Dickson, Mitchell, and Muh Geot Wong. "The role of endothelin receptor antagonists in IgA nephropathy." Nephrology 29, S2 (2024): 30–33. http://dx.doi.org/10.1111/nep.14364.

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AbstractThere is growing evidence of endothelin receptor antagonists (ERAs) in renoprotection in proteinuric kidney disease including IgA nephropathy (IgAN). Here, we review current evidence, including the use of sparsentan, atrasentan and zibotentan in IgAN. Recent trails of combination therapy including SGLT2 inhibitors and ERAs suggest possible benefit in further reduction of proteinuria and reducing ERA fluid‐retention side effects although more evidence is needed for clinical applications.
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14

Kohan, Donald, Jula Inrig, Brad H. Rovin, and Radko Komers. "Sparsentan and kidney protection: improved medullary oxygenation? – Authors' reply." Lancet 404, no. 10465 (2024): 1809. http://dx.doi.org/10.1016/s0140-6736(24)01167-x.

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15

Hendry, Bruce, Donald Kohan, Rob Geletka, Celia Jenkinson, Shang-Chiung Chen, and Patricia W. Bedard. "WCN24-846 SPARSENTAN RECEPTOR OCCUPANCY MODELING, CLINICAL ACTIONS, AND SAFETY." Kidney International Reports 9, no. 4 (2024): S146. http://dx.doi.org/10.1016/j.ekir.2024.02.301.

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16

Cuéllar Rodríguez, Santiago. "Novel Drugs Recently Authorized by EMA and FDA (Q1, 2023)." Anales de la Real Academia Nacional de Farmacia 89, no. 89(01) (2023): 127–34. http://dx.doi.org/10.53519/analesranf.2023.89.01.07.

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EMA (EUROPEAN MEDICINES AGENCY): (L) AGENTES ANTINEOPLÁSICOS E INMUNOMODULADORES: Loncastuximab Tesirina (Zynlonta®): linfoma B.FDA (U.S. FOOD & DRUG ADMINISTRATION): (A) TRACTO ALIMENTARIO Y METABOLISMO: Bexagliflozina (Brenzavy®): diabetes mellitus tipo 2. (B) SANGRE Y SISTEMA HEMATOPOYÉTICO: Daprodustat (Jesduvroq®): anemia asociada a insuficiencia renal.(C) SISTEMA CARDIOVASCULAR: Sparsentan (Filspari®): nefropatía por inmunoglobulina A. (L) AGENTES ANTINEOPLÁSICOS E INMUNOMODULADORES: Elacestrant (Orserdu®): cáncer de mama. Pirtobrutinib (Jaypirica®): leucemia de células del manto. (N
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17

Eddy, Sean, Felix H. Eichinger, Brad A. Godfrey, et al. "Development of a Treatment Response Prediction Strategy for Sparsentan in Glomerular Disease." Journal of the American Society of Nephrology 33, no. 11S (2022): 520. http://dx.doi.org/10.1681/asn.20223311s1520c.

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18

ARBAOUI, Ibtissame. "Therapeutic advances in the management of chronic kidney disease: A look at the last 10 years." Batna Journal of Medical Sciences (BJMS) 11, no. 2 (2024): 216–19. https://doi.org/10.48087/bjmsra.2024.11219.

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Over the last ten years, nephrology has experienced several therapeutic advances which have changed the management of patients with chronic kidney disease, their quality of life and their prognoses. Among these treatments we cite Hypoxia-Inducible Factor stabilizer which is an oral treatment for anemia, tolvaptan, treatment of autosomal dominant polycystic kidney disease, budesonide and sparsentan for the treatment of IgA nephropathy, denervation renal disease proposed for resistant arterial hypertension and a molecule which has revolutionized the management of diabetic kidney disease with and
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19

Mareedu, Neeharik, and Praveen Errabelli. "WCN24-2219 TRF-BUDESONIDE AND SPARSENTAN AS AN INITIAL THERAPY FOR PRIMARY IgA NEPHRITIS." Kidney International Reports 9, no. 4 (2024): S183—S184. http://dx.doi.org/10.1016/j.ekir.2024.02.377.

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20

Diefenhardt, Paul, Thomas Osterholt, and Paul Brinkkötter. "Nephrotisches Syndrom: Überblick und Basis." DMW - Deutsche Medizinische Wochenschrift 147, no. 06 (2022): 332–36. http://dx.doi.org/10.1055/a-1334-2135.

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Was ist neu? Einteilung der Minimal-Change-Disease und fokalen und segmentalen Glomerulosklerose Das zunehmende Wissen über die verschiedenen Auslöser der MCD und FSGS spiegelt sich in den neuen KDIGO-Leitlinien wider, welche eine klare Einteilung der (MCD und) FSGS in primäre, sekundäre und genetische Ursachen vorsieht. Die korrekte Klassifizierung ist wichtig und hat eine direkte Auswirkung auf die Therapie. Therapie Die Therapie besteht bei der primären MCD und FSGS weiterhin aus Steroiden oder – bei Nichtansprechen bzw. Kontraindikationen – aus Calcineurin-Inhibitoren, Mycophenolatmofetil
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21

Nagasawa, Hajime, Hitoshi Suzuki, Celia P. Jenkinson, et al. "Sparsentan Protects Against Development of Albuminuria and Glomerulosclerosis in the gddY Mouse Model of IgA Nephropathy." Journal of the American Society of Nephrology 31, no. 10S (2020): 564. http://dx.doi.org/10.1681/asn.20203110s1564c.

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22

Campbell, Kirk N., Siân Griffin, Howard Trachtman, Rob Geletka, and Muh Geot Wong. "Practical Considerations for the Use of Sparsentan in the Treatment of Patients with IgAN in Clinical Practice." International Journal of Nephrology and Renovascular Disease Volume 16 (December 2023): 281–91. http://dx.doi.org/10.2147/ijnrd.s430377.

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23

Mareedu, Neeharik, and Praveen Errabelli. "WCN24-2352 Improved Proteinuria Reduction with the use of Sparsentan and Targeted Release Budesonide in advanced IgAN." Kidney International Reports 9, no. 4 (2024): S188—S189. http://dx.doi.org/10.1016/j.ekir.2024.02.389.

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24

Cheung, Chee Kay, Colleen Burns, Neeraj Dhaun, et al. "Sparsentan as First-Line Treatment of Incident Patients with IgA Nephropathy: Preliminary Findings from the SPARTAN Trial." Journal of the American Society of Nephrology 34, no. 11S (2023): 978–79. http://dx.doi.org/10.1681/asn.20233411s1978c.

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25

Komers, Radko, Ulysses Diva, Jula K. Inrig, Andrea Loewen, Howard Trachtman, and William E. Rote. "Study Design of the Phase 3 Sparsentan Versus Irbesartan (DUPLEX) Study in Patients With Focal Segmental Glomerulosclerosis." Kidney International Reports 5, no. 4 (2020): 494–502. http://dx.doi.org/10.1016/j.ekir.2019.12.017.

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26

Pan-Zhou, Xin-ru, and Kevin Leach. "SP124IN VITRO EVALUATION OF INDUCTION OF CYTOCHROME P450 ENZYMES BY SPARSENTAN AND EFFECTS OF ITS METABOLISM BY POTENTIAL." Nephrology Dialysis Transplantation 32, suppl_3 (2017): iii146—iii147. http://dx.doi.org/10.1093/ndt/gfx141.sp124.

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27

Wong, M. G., H. J. Heerspink, R. Komers, A. Mercer, and J. Radhakrishnan. "WCN23-1087 SPARSENTAN REDUCES PROTEINURIA IN PATIENTS WITH IMMUNOGLOBULIN A NEPHROPATHY (IGAN): INTERIM RESULTS OF THE PROTECT STUDY." Kidney International Reports 8, no. 3 (2023): S126—S127. http://dx.doi.org/10.1016/j.ekir.2023.02.286.

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28

Lieberman, Kenneth V., Howard Trachtman, Rosanna Coppo, et al. "Preliminary Findings from the Phase 2 EPPIK Study of Sparsentan in Pediatric Patients with Selected Proteinuric Glomerular Diseases." Journal of the American Society of Nephrology 34, no. 11S (2023): 84–85. http://dx.doi.org/10.1681/asn.20233411s184c.

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29

Trachtman, Howard, Moin Saleem, Rosanna Coppo, Michelle N. Rheault, Ping He, and Radko Komers. "Sparsentan for Treatment of Pediatric Patients with Selected Proteinuric Glomerular Diseases: Design of the Phase 2 EPPIK Study." Journal of the American Society of Nephrology 32, no. 10S (2021): 609. http://dx.doi.org/10.1681/asn.20213210s1609c.

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30

Longhitano, Elisa, Vincenzo Calabrese, Chiara Casuscelli, et al. "Proteinuria and Progression of Renal Damage: The Main Pathogenetic Mechanisms and Pharmacological Approach." Medicina 60, no. 11 (2024): 1821. http://dx.doi.org/10.3390/medicina60111821.

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The integrity of the glomerular filtration barrier maintains protein excretion below 150 mg/day. When urinary proteins increase, this indicates damage to the filtration barrier. However, proteinuria is not only a marker of kidney damage but also exacerbates it through various mechanisms involving the glomerular and tubulointerstitial compartments. Therefore, it is essential to intervene with renoprotective action that reduces the proteinuria. In this context, Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are cornerstone treatments. Recent advancements include sodiu
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31

Bulanov, N., A. A. Efimova, T. Bochkareva, D. Bulavina, E. A. Makarov, and S. Moiseev. "Treatment of primary IgA nephropathy. Part 1. Supportive therapy." Clinical pharmacology and therapy 35, no. 2 (2025): 7–12. https://doi.org/10.32756/0869-5490-2025-2-7-12.

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IgA nephropathy (IgAN), the most common form of chronic glomerulonephritis, may be associated with unfavorable longterm outcomes. Recently, new agents slowing the progression of the disease and improving kidney survival have been developed. Supportive therapy with antihypertensive drugs and renin-angiotensin-aldosterone system (RAAS) blockers remains the first line treatment in patients without rapidly progressive glomerulonephritis. Most patients receive angiotensin-converting enzyme inhibitors and angiotensin receptor blockers that reduce proteinuria, whereas the data regarding their effects
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32

Cheung, Chee Kay, Stephanie Moody, Neeraj Dhaun, et al. "WCN24-773 SPARSENTAN AS FIRST-LINE TREATMENT OF INCIDENT PATIENTS WITH IgA NEPHROPATHY: PRELIMINARY FINDINGS FROM THE SPARTAN TRIAL." Kidney International Reports 9, no. 4 (2024): S142. http://dx.doi.org/10.1016/j.ekir.2024.02.293.

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33

Roberts, Eleanor. "Sparsentan, a Dual Endothelin Type A and Angiotensin II Subtype 1 Receptor Antagonist for the Treatment of Immunoglobulin A Nephropathy: Latest Trial Results, Pharmacokinetic Considerations, and Binding Profile." European Medical Journal, March 14, 2024, 13–21. http://dx.doi.org/10.33590/emj/11000020.

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Immunoglobulin A nephropathy (IgAN) is one of the most common forms of primary glomerulonephritis. In some patients, it can progress rapidly, leading to proteinuria, kidney failure, and death. Standard of care is traditionally with an angiotensin converting enzyme inhibitor (ACEi), or an angiotensin II (Ang II) receptor blocker (ARB). More recently, drugs targeting both endothelin 1 (ET-1) and Ang II receptors have been developed, as overactivation of such is implicated in IgAN. Sparsentan is a dual ET Type A (ETAR) and Ang II subtype 1 receptor (AT1R) antagonist. The PROTECT study compared sp
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34

"Sparsentan." American Journal of Health-System Pharmacy, May 4, 2023. http://dx.doi.org/10.1093/ajhp/zxad073.

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35

Patel, Nikunjkumar K., Kuan‐Fu Chen, Shang‐Chiung Chen, and Kai Liu. "Physiologically‐based pharmacokinetic model of sparsentan to evaluate drug–drug interaction potential." CPT: Pharmacometrics & Systems Pharmacology, December 2, 2023. http://dx.doi.org/10.1002/psp4.13086.

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AbstractSparsentan is a dual endothelin/angiotensin II receptor antagonist indicated to reduce proteinuria in patients with primary IgA nephropathy at high risk of disease progression. In vitro data indicate that sparsentan is likely to inhibit or induce various CYP enzymes at therapeutic concentrations. Sparsentan as a victim and perpetrator of CYP3A4 mediated drug–drug interactions (DDIs) has been assessed clinically. A mechanistic, bottom‐up, physiologically‐based pharmacokinetic (PK) model for sparsentan was developed based on in vitro data of drug solubility, formulation dissolution and p
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36

Chiu, Ada W., and Nina Bredenkamp. "Sparsentan: A First-in-Class Dual Endothelin and Angiotensin II Receptor Antagonist." Annals of Pharmacotherapy, September 14, 2023. http://dx.doi.org/10.1177/10600280231198925.

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Objective: To provide an overview of the guidelines on the management of immunoglobulin A nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS), review the evidence for sparsentan, and discuss its place in therapy. Data Sources: A literature search was conducted using MEDLINE, EMBASE, and clinicaltrials.gov using the search terms “sparsentan” and “RE-021” up to the end of Jun 2023. Study Selection and Data Extraction: English studies were included if they evaluated the pharmacology, pharmacokinetics, efficacy, and safety of sparsentan in human subjects. Information from the Food and
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37

Gyarmati, Georgina, Urvi Shroff, Audrey Izuhara, Radko Komers, Patricia Bedard, and Janos Peti-Peterdi. "FC 016SPARSENTAN IMPROVES GLOMERULAR BLOOD FLOW AND AUGMENTS PROTECTIVE TISSUE REMODELING IN MOUSE MODELS OF FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS)." Nephrology Dialysis Transplantation 36, Supplement_1 (2021). http://dx.doi.org/10.1093/ndt/gfab138.002.

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Abstract Background and Aims Preliminary preclinical and emerging clinical evidence indicates strong antiproteinuric actions of dual endothelin type A (ETA) and angiotensin II type 1 (AT1) receptor antagonism with sparsentan. These nephroprotective effects have been more pronounced in different experimental and clinical settings compared to current standard of care using an AT1 receptor blocker (ARB). Considering the broad spectrum of renal actions of endothelin (ET) and angiotensin II (Ang II), inhibition of both pathways using sparsentan is postulated to target multiple renal cell types via
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38

Nagasawa, Hajime, Seiji Ueda, Hitoshi Suzuki, et al. "Sparsentan is superior to losartan in the gddY mouse model of IgA nephropathy." Nephrology Dialysis Transplantation, January 25, 2024. http://dx.doi.org/10.1093/ndt/gfae021.

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Abstract Background The mechanism leading to the development of IgA nephropathy (IgAN) remains to be completely understood. Endothelin-1 (ET-1) as well as angiotensin II (AngII) promote glomerular injury, tubulointerstitial inflammation, and fibrosis leading to chronic kidney disease. Sparsentan, a dual endothelin angiotensin receptor antagonist (DEARA), recently received accelerated approval in United States for the reduction of proteinuria in adults with IgAN at high risk of disease progression. To elucidate the mechanisms by which sparsentan is efficacious in IgAN, we examined the effect of
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39

Rovin, Brad H., Radko Komers, Chris Scroggins, and Jonathan Barratt. "Sparsentan in IgA nephropathy: a plain language summary of publication for the PROTECT study." Therapeutic Advances in Rare Disease 6 (July 2025). https://doi.org/10.1177/26330040251355613.

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Summary What is this summary about? Sparsentan (FILSPARI ® ) is a once-daily pill for people with Immunoglobulin A (IgA) nephropathy who are at high risk for worsening kidney disease. Early results from a research study (clinical trial) called PROTECT showed that after 9 months of treatment, sparsentan lowered proteinuria more than irbesartan , a blood pressure medication commonly used to treat IgA nephropathy . These results contributed to sparsentan receiving approval in the United States, the European Union, Switzerland, and the United Kingdom in 2024. This is a plain language summary of pu
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40

Mane, Sudam S., Manoj Ghaste, and David V. Dearden. "Mass spectrometry‐based gas phase intramolecular benzyl migration in sparsentan, a novel endothelin and angiotensin II receptor antagonist." Journal of Mass Spectrometry 58, no. 11 (2023). http://dx.doi.org/10.1002/jms.4980.

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AbstractWe report a collision‐induced dissociation (CID) based gas phase rearrangement study using quadrupole time‐of‐flight mass spectrometry coupled with liquid chromatography on a novel endothelin and angiotensin II receptor antagonist, sparsentan. We performed tandem mass spectrometry to identify precursor and fragment ion relationships and assigned structures for major fragment ions. We propose a benzyl migration mechanism based on bond length measurements in density functional theory (B3LYP/6‐31+G*) optimized geometries of protonated sparsentan and its m/z 547 fragment. Protonated sparse
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41

Syed, Yahiya Y. "Sparsentan: First Approval." Drugs, April 6, 2023. http://dx.doi.org/10.1007/s40265-023-01864-x.

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42

Roberts, Eleanor. "Addressing Proteinuria in Patients with Immunoglobulin A Nephropathy Through Concomitant Use of Sparsentan and Sodium-Glucose Cotransporter-2 Inhibitors." European Medical Journal, December 12, 2024, 28–36. https://doi.org/10.33590/emj/rmah5090.

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IgA nephropathy (IgAN) can impact life expectancy in those affected, thus efficacious treatment is key. Endothelin 1 (ET-1) and angiotensin II (Ang II) are instrumental in the development of IgAN-associated renal damage. Use of sparsentan, a dual ET Type A receptor (ETAR) and Ang II subtype 1 receptor (AT1R) antagonist (DEARA), can lead to reductions in proteinuria and thereby help to slow kidney function decline in patients with IgAN. Sparsentan is included in the 2024 draft Kidney Disease Improving Global Outcome (KDIGO) guidelines for patients with IgAN at risk of progressive kidney functio
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43

Chai, Xinglei, Mark Bensink, Sophie Gao, et al. "#4499 MATCHING-ADJUSTED INDIRECT COMPARISON OF SPARSENTAN VS DELAYED-RELEASE FORMULATION BUDESONIDE FOR PROTEINURIA REDUCTION IN ADULTS WITH IGA NEPHROPATHY." Nephrology Dialysis Transplantation 38, Supplement_1 (2023). http://dx.doi.org/10.1093/ndt/gfad063c_4499.

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Abstract Background and Aims Immunoglobulin A (IgA) nephropathy is a rare kidney disorder characterized by deposition of IgA in the glomeruli and associated with a reduction in renal function and increased risk of kidney failure [1,2]. In the absence of head-to-head trials, this study used matching-adjusted indirect comparison (MAIC)[3] of randomized control trial data to compare 9-month efficacy outcomes between potential treatment options for IgA nephropathy, sparsentan and recently FDA and EMA approved delayed-release formulation budesonide [4,5]. Method An unanchored MAIC was conducted usi
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Kaduk, James A., Anja Dosen, and Thomas Blanton. "Crystal structure of sparsentan, C32H40N4O5S." Powder Diffraction, March 26, 2025, 1–5. https://doi.org/10.1017/s0885715625000132.

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Abstract The crystal structure of sparsentan has been solved and refined using synchrotron X-ray powder diffraction data and optimized using density functional theory techniques. Sparsentan crystallizes in space group P-1 (#2) with a = 11.4214(8), b = 12.0045(9), c = 14.1245(12) Å, α = 97.6230(22), β = 112.4353(16), γ = 110.2502(11)°, V = 1599.20(6) Å3, and Z = 2 at 298 K. The crystal structure consists of an isotropic packing of dimers of sparsentan molecules, linked by N–H···O=S hydrogen bonds. Several intra- and intermolecular C–H···O and C–H···N hydrogen bonds also link the molecules. The
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Schanz, Moritz, Claudia Seikrit, Bernd Hohenstein, et al. "First real-world evidence of sparsentan efficacy in patients with IgA nephropathy treated with SGLT2 inhibitors." Clinical Kidney Journal, December 3, 2024. https://doi.org/10.1093/ckj/sfae394.

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Abstract Background Sparsentan, a dual-acting antagonist for both the angiotensin II receptor type 1 and the endothelin receptor type A, has emerged as a promising therapeutic agent for the treatment of IgA nephropathy (IgAN). Following the publication of the PROTECT trial, sparsentan recently received approval for the treatment of IgAN in Europe. However, it remains uncertain whether an additive effect can be observed in the context of existing treatment with sodium-glucose co-transporter 2 (SGLT2) inhibitors, given that the PROTECT study did not investigate this dual therapy approach. Method
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Gong, Wu, Ulysses Diva, Mark Bensink, et al. "#367 PROTECT and NefIgArd two-year proteinuria and eGFR outcomes in adults with IgA nephropathy: matching-adjusted indirect comparison." Nephrology Dialysis Transplantation 39, Supplement_1 (2024). http://dx.doi.org/10.1093/ndt/gfae069.453.

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Abstract Background and Aims Immunoglobulin A (IgA) nephropathy is a rare kidney disorder characterized by deposition of IgA in the glomeruli causing progressive loss of kidney function and increased risk of kidney failure. In the absence of a head-to-head trial, this study used unanchored matching-adjusted indirect comparison (MAIC) of clinical trial data to compare two-year efficacy outcomes between Sparsentan in PROTECT and targeted-release formulation (TRF) budesonide plus real-world optimized and stable renin-angiotensin system inhibition (RASi) standard-of-care (SoC) in NefIgArd. Method
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Barratt, Jonathan, Hiddo Lambers Heerspink, Muh Wong, Radko Komers, Alex Mercer, and Jai Radhakrishnan. "#4057 SUPERIOR PROTEINURIA REDUCTION WITH SPARSENTAN IN IMMUNOGLOBULIN A NEPHROPATHY (IGAN): A PROTECT STUDY INTERIM ANALYSIS." Nephrology Dialysis Transplantation 38, Supplement_1 (2023). http://dx.doi.org/10.1093/ndt/gfad063a_4057.

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Abstract Background and Aims IgAN is the most common glomerular disease worldwide. Despite optimized standard of care, most patients with IgAN progress to kidney failure within 10-15 years, consequently seriously affecting their quality of life and mortality. Treatments that reduce proteinuria and risk of kidney disease progression are urgently needed for IgAN. Sparsentan is a novel, oral, non-immunosuppressive, single molecule that is a dual endothelin and angiotensin receptor antagonist being investigated for IgAN and focal segmental glomerulosclerosis. The Phase 3 PROTECT study is examining
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Crompton, Michael, Judy J. Watson, Elizabeth Colby, et al. "#457 Sparsentan has direct effects on the glomerular capillary wall to attenuate increased permeability after exposure to nephrotic syndrome plasma." Nephrology Dialysis Transplantation 39, Supplement_1 (2024). http://dx.doi.org/10.1093/ndt/gfae069.015.

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Abstract Background and Aims The glomerular endothelial glycocalyx (eGlx), a luminal layer of proteoglycans, glycoproteins and glycolipids, forms the first part of the glomerular filtration barrier (GFB). Nephrotic syndrome (NS) describes a group of pathologies of the renal glomerulus that result in proteinuria and is associated with glomerular endothelial dysfunction. Current treatments are broad and non-specific. Sparsentan is a single-molecule dual endothelin type-A and angiotensin II type 1 receptor antagonist that has received accelerated approval in the United States for the reduction of
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Syed, Yahiya Y. "Correction to: Sparsentan: First Approval." Drugs, June 6, 2023. http://dx.doi.org/10.1007/s40265-023-01900-w.

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Reily, Colin, Zina Moldoveanu, Tiziano Pramparo, et al. "Sparsentan ameliorates glomerular hypercellularity and inflammatory-gene networks induced by IgA1-IgG immune complexes in a mouse model of IgA nephropathy." American Journal of Physiology-Renal Physiology, March 21, 2024. http://dx.doi.org/10.1152/ajprenal.00253.2023.

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IgA nephropathy (IgAN), is characterized by glomerular deposition of immune complexes (IC) consisting of IgA1 with O-glycans deficient in galactose (Gd-IgA1) and Gd-IgA1-specific IgG autoantibodies. These ICs induce kidney injury, and in the absence of disease-specific therapy, up to 40% of IgAN patients progress to kidney failure. IgA1 with its clustered O-glycans is unique to humans, which hampered development of small-animal models of IgAN. Here, we used a model wherein engineered IC (EIC) formed from human Gd-IgA1 and recombinant human IgG autoantibody are injected into nude mice to induce
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