Vanrafia (atrasentan) / AbbVie, Novartis - LARVOL DELTA

ENDOTHELIAL DNA DAMAGE ORCHESTRATES CARDIO-KIDNEY-METABOLIC DYSFUNCTION THROUGH ENDOTHELIN-1 SIGNALING (ISN-WCN 2026) - "Pharmacological ETAR blockade with Atrasentan reversed these phenotypes—normalizing blood pressure, resolving hepatic steatosis, restoring HDL-C, reducing visceral fat, and attenuating renal senescence—by interrupting the ET-1-ETAR-ACSS2 cascade...The EC response to DNA damage drives pathology primarily through endocrine dysregulation via the ET-1-ETAR-ACSS2 signaling cascade, rather than immune activation. Targeting this pathway with ETAR blockade offers a mechanism-based, comprehensive therapeutic strategy for age-related CKM syndrome."

Cardiovascular • Dyslipidemia • Hypertension • Metabolic Disorders • Renal Disease • ACSS2 • EDN1

EARLY INSIGHTS INTO CHARACTERISTICS AND TREATMENT PATTERNS OF US PATIENTS WITH COMPLEMENT 3 GLOMERULOPATHY WHO WERE PRESCRIBED IPTACOPAN: THE APPRISE-C3G DATA PLATFORM (ISN-WCN 2026) - "This interim analysis provides early insights into demographic and clinical characteristics and treatment patterns of patients enrolled in APPRISE-C3G to date.Methods The APPRISE data platform captures retrospective, longitudinal, deidentified patient-level data from patients with C3G, immunoglobulin A nephropathy (IgAN), or paroxysmal nocturnal hemoglobinuria treated with iptacopan and/or atrasentan. Median (IQR) latest reported pre-index urine protein-to-creatinine ratio (n=7) was 4.2 (2.7–7.3) g/g.Conclusion This interim analysis of APPRISE-C3G provides first insights into characteristics and treatment patterns of US patients with C3G prescribed iptacopan in a real-world setting. Recruitment for APPRISE-C3G is ongoing and will provide further valuable information about this patient population over time.I have potential conflict of interest to disclose.This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.I did not use generative AI and..."

Clinical • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • IgA Nephropathy • Lupus Nephritis • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

ATRASENTAN VS PLACEBO IN SUBGROUPS OF PATIENTS FROM EAST ASIA WITH IGA NEPHROPATHY (IGAN): INTERIM DATA FROM THE PHASE III ALIGN TRIAL (ISN-WCN 2026) - P3 | "Regardless of the individual or grouped components of the MEST-C scoring system, the relative percentage reduction in 24h-UPCR favored atrasentan over placebo (Figure).Download: Download high-res image (270KB)Download: Download full-size imageConclusion In pts from East Asia, clinically meaningful reductions in 24h-UPCR were observed with atrasentan vs placebo at Week 36 of the ALIGN trial, supporting atrasentan as a potential foundational treatment for pts from East Asia with IgAN. Despite small sample sizes across some of the subgroups, the benefits appeared consistent irrespective of BL proteinuria, hematuria and MEST-C score components at kidney biopsy.I have potential conflict of interest to disclose.Hiddo JL Heerspink has received consulting fees from AstraZeneca, Alexion, Amgen, Bayer, Boehringer Ingelheim, Biocity Pharmaceutics, Dimerix, Eli Lilly, Novartis, Novo Nordisk, Roche, and Travere Therapeutics; received research funding from AstraZeneca, Bayer,..."

Clinical • P3 data • P3 data: top line • Fibrosis • Focal Segmental Glomerulosclerosis • Glomerulonephritis • IgA Nephropathy • Immunology • Renal Disease

EFFICACY OF ATRASENTAN BY RENIN–ANGIOTENSIN SYSTEM INHIBITOR DOSE IN IGA NEPHROPATHY PATIENTS FROM EAST ASIA: POST HOC ANALYSIS FROM THE PHASE III ALIGN TRIAL (ISN-WCN 2026) - P3 | "These data support atrasentan as a potential IgAN treatment in pts from East Asia regardless of their RASi dose. Our findings further reinforce the potential of atrasentan as a foundational therapy in IgAN.I have potential conflict of interest to disclose.Hong Zhang reports consulting fees from Alexion/AstraZeneca, Alpine Immune Sciences/Vertex Pharmaceuticals, Calliditas Therapeutics, Chinook Therapeutics/Novartis, Everest Medicines, Emerald Clinical, Omeros, Otsuka Pharmaceuticals, Roche, and Vera Therapeutics.I did not use generative AI and AI-assisted technologies in the writing process."

Clinical • P3 data • Retrospective data • Glomerulonephritis • IgA Nephropathy • Renal Disease

GLOMERULAR ENDOTHELIAL CELL-DERIVED ET-1 PROMOTES PODOCYTE INJURY VIA ETAR/PKM2 SIGNALING IN SUNITINIB-ASSOCIATED NEPHROTOXICITY (ISN-WCN 2026) - "Therapeutic experiments evaluated Atrasentan (ETAR antagonist) and Shikonin (PKM2 inhibitor) for 4 weeks, with renal pathology assessed by PAS staining and electron microscopy.Results Serum analysis of 31 mRCC patients showed significant circulating ET-1 elevation following sunitinib therapy, with higher levels observed in those with severe proteinuria. Mechanistically, GEC-derived ET-1 activated ETAR/β-arrestin-1 signaling in adjacent podocytes, promoting PKM2 dimerization and nuclear translocation, which in turn activated NF-κB signaling and oxidative stress. Pharmacological blockade of ETAR or inhibition of PKM2 attenuated podocyte injury and reduced proteinuria.Conclusion GEC-derived ET-1 promotes podocyte injury via ETAR/PKM2 signaling in sunitinib-induced nephrotoxicity.Targeting ET-1/ETAR signaling and PKM2-mediated glycolytic reprogramming may represent novel therapeutic strategies to mitigate sunitinib-associated nephrotoxicity, with potential implications for..."

Genito-urinary Cancer • Nephrology • Renal Cell Carcinoma • Solid Tumor • EDN1 • PKM

Efficacy and Safety Results of Atrasentan in Patients With IgA Nephropathy on Sodium' äìglucose Co-transporter 2 Inhibitors: Phase II, Randomized, Placebo-controlled, Crossover Trial (Assist) (ISN-WCN 2026) - No abstract available

Clinical • Late-breaking abstract • P2 data • Glomerulonephritis • IgA Nephropathy • Renal Disease

Efficacy and Safety Results of Atrasentan in Patients With Iga Nephropathy on Sodium'äìglucose Co-transporter 2 Inhibitors: Phase II, Randomized, Placebo-controlled, Crossover Trial (ASSIST) (ISN-WCN 2026) - No abstract available

Clinical • P2 data • Glomerulonephritis • IgA Nephropathy • Nephrology • Renal Disease

Novel protein biomarkers for risk stratification and personalized medicine. (PubMed, Nephrol Dial Transplant) - "Urinary clusterin and uEGF are mechanism-informed pharmacodynamic biomarkers reflecting distinct intrarenal pathways engaged by ERA and SGLT2i therapy, respectively. These biomarkers complement albuminuria by capturing tubular injury and repair, providing a more comprehensive biological assessment of treatment effects and heterogeneity in CKD."

Biomarker • Journal • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Glomerulonephritis • Lupus Nephritis • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • CLU • EDN1 • EGF

IgA Nephropathy Insights From Treatment Experience Among Patients Receiving Iptacopan and/or Atrasentan Using Primary Data Collection (clinicaltrials.gov) - P=N/A | N=80 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New trial • Glomerulonephritis • IgA Nephropathy • Renal Disease

Comparative Network Meta-Analysis (NMA) of Sibeprenlimab Efficacy in the Treatment of Immunoglobulin A Nephropathy (IgAN) (NKF-SCM 2026) - "Treatments analyzed were: sibeprenlimab, atacicept, atrasentan, sparsentan, cemdisiran, TRF-budesonide, ravulizumab, and iptacopan. CONCLUSION Sibeprenlimab demonstrates clinically significant reductions in uPCR compared with other treatments, suggesting potential in IgAN. Updated NMA will be conducted when full Phase 3 results for sibeprenlimab are available."

Retrospective data • Glomerulonephritis • IgA Nephropathy • Renal Disease

Overview of Characteristics and Treatment Patterns of US Patients (Pts) With Immunoglobulin A Nephropathy (IgAN) Prescribed Atrasentan: APPRISE-IgAN Data Platform (NKF-SCM 2026) - "INTRODUCTION The A Pt Platform for Real-world data on Iptacopan and Atrasentan in the United StatEs for pts with IgAN (APPRISE-IgAN) data platform captures real-world data on US pts with IgAN prescribed atrasentan (highly selective endothelin A receptor antagonist; accelerated FDA approval Apr 2025) and/or iptacopan (complement pathway factor B inhibitor; accelerated FDA approval Aug 2024). CONCLUSION This analysis highlights characteristics and treatment patterns of pts with IgAN receiving atrasentan. APPRISE-IgAN recruitment and data collection are ongoing and will provide further valuable insights into this population over time."

Clinical • Glomerulonephritis • IgA Nephropathy • Renal Disease

Real World Treatment Patterns Among Adult Patients with IgA Nephropathy in the US (NKF-SCM 2026) - "The proportion of patients with ≥ 1 administration or fill of any of the following treatments was reported: SGLT2 inhibitors (SGLT2i), GLP-1 agonists, and more recent therapies specifically approved for IgAN - budesonide, sparsentan, iptacopan, and atrasentan. A large proportion of patients have moderate to severe disease, despite currently available treatments. More options are warranted to potentially better meet the needs of patients with IgAN in the US."

Clinical • HEOR • Real-world • Real-world evidence • Cardiovascular • Chronic Kidney Disease • Chronic Obstructive Pulmonary Disease • Glomerulonephritis • Hypertension • IgA Nephropathy • Immunology • Infectious Disease • Pulmonary Disease • Renal Disease • Respiratory Diseases

Update on Characteristics and Treatment Patterns of US Patients (Pts) With Immunoglobulin A Nephropathy (IgAN) Prescribed Iptacopan: APPRISE-IgAN Data Platform (NKF-SCM 2026) - "INTRODUCTION A Pt Platform for Real-world data on Iptacopan and Atrasentan in the United StatEs for pts with IgAN (APPRISE-IgAN) is a data platform capturing real-world data on US pts with IgAN prescribed iptacopan (alternative complement pathway factor B inhibitor) and/or atrasentan (selective endothelin A receptor antagonist)...Other common prior therapies were sodium-glucose cotransporter-2 inhibitors (78%) and delayed-release budesonide (48%)...CONCLUSION This analysis highlights characteristics and treatment patterns of pts with IgAN prescribed iptacopan. Ongoing APPRISE-IgAN recruitment and data collection will provide further valuable insights into this population over time."

Clinical • Glomerulonephritis • IgA Nephropathy • Renal Disease

Urinary clusterin as a biomarker of human kidney disease progression and response to the endothelin receptor antagonist atrasentan: An exploratory analysis from the SONAR trial. (PubMed, Nat Commun) - P3 | "Early uCLU changes independently predict improved kidney outcomes. In summary, uCLU is associated with kidney disease progression and response to atrasentan treatment, supporting its potential as a pharmacodynamic biomarker to target therapy."

Biomarker • Journal • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • CLU

ASSIST: Randomized, Double-blind, Placebo-controlled, Crossover Study of Atrasentan in Subjects With IgA Nephropathy (clinicaltrials.gov) - P2 | N=54 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed | Trial completion date: Aug 2026 ➔ Oct 2025 | Trial primary completion date: Oct 2025 ➔ Jun 2025

Trial completion • Trial completion date • Trial primary completion date • Glomerulonephritis • IgA Nephropathy • Renal Disease

Managed Access Programs for EXV811, Atrasentan (clinicaltrials.gov) - P=N/A | N=0 | Temporarily Not Available | Sponsor: Novartis Pharmaceuticals

New trial • Glomerulonephritis • IgA Nephropathy • Renal Disease

Effects of Atrasentan on Kidney Gene Transcription, Mesangial Cell Proliferation, and Proteinuria in Immunoglobulin A Nephropathy. (PubMed, Kidney360) - "The acute mechanistic effects of atrasentan demonstrated in vitro and in vivo support the therapeutic potential of atrasentan in IgAN. The ongoing AFFINITY and ASSIST phase 2 trials, and the ALIGN phase 3 trial in patients with IgAN will further evaluate the translation of these mechanistic effects to the clinical efficacy and safety of atrasentan."

Journal • Chronic Kidney Disease • Fibrosis • Glomerulonephritis • IgA Nephropathy • Immunology • Inflammation • Lupus Nephritis • Nephrology • Renal Disease • EDN1 • THY1

From RAAS blockade to regenerative medicine: evolving treatment strategies in Alport syndrome. (PubMed, Pediatr Nephrol) - "Adjunctive commercially available metabolic modulators, including SGLT2i, mineralocorticoid receptor antagonists, ezetimibe and GLP-1 receptor agonists, may offer additional kidney protection. Ameliorating therapies being tested in Phase II trials include endothelin receptor antagonists (e.g., atrasentan), dual endothelin receptor antagonist and angiotensin II receptor inhibition (e.g., sparsentan) FXR agonists (e.g., vonafexor), inducers of cholesterol efflux (e.g., VAR200 and R3R01), and NOX1/4 inhibitors (e.g., setanaxib), several of which are currently being evaluated in clinical trials. Novel strategies such as exon skipping, gene editing, and nonsense mutation readthrough (e.g., ELX-02) are advancing toward precision medicine approaches as disease modifying agents targeting the genetic cause of AS...This review summarizes the current landscape of AS classification and treatment, highlighting both standard interventions and experimental therapies. Emphasis is placed..."

Journal • Review • Fibrosis • Gene Therapies • Genetic Disorders • Glomerulonephritis • Immunology • Renal Disease • COL4A5

Novartis will present new data from 33 abstracts across its Cardiovascular, Renal, and Metabolic (CRM) disease portfolio at the upcoming American Society of Nephrology (ASN) Kidney Week 2025 in Houston, Texas and American Heart Association’s (AHA) Scientific Sessions 2025 in New Orleans, Louisiana, advancing scientific insight into these critical disease areas (Novartis Press Release)

Clinical data • Autosomal Dominant Polycystic Kidney Disease • Cardiovascular • Chronic Kidney Disease • IgA Nephropathy

New Era for FSGS Treatment (KIDNEY WEEK 2025) - "Participating nephrologists currently estimate 60% of their FSGS patients will be candidates for sparsentan and 58% for atrasentan, if/when they are approved and available. Conclusion Nephrologists are eager to begin using new FSGS treatment options and will look to clinical trial data (for FSGS and other glomerular diseases if available) that prove efficacy in reducing proteinuria and slowing eGFR decline."

Chronic Kidney Disease • Focal Segmental Glomerulosclerosis • Glomerulonephritis • IgA Nephropathy • Nephrology • Renal Disease

Efficacy and Safety of Atrasentan in Patients (Pts) with IgAN from East (E) Asia: Phase 3 ALIGN Interim Data (KIDNEY WEEK 2025) - P3 | "Data were consistent for all pts of Asian race. Conclusion Atrasentan was well tolerated and led to a clinically meaningful 24h-UPCR reduction vs pbo in pts from E Asia, supporting the potential of atrasentan as a foundational treatment for Asian pts with IgAN."

Clinical • P3 data • P3 data: top line • Glomerulonephritis • IgA Nephropathy • Renal Disease

Renin-Angiotensin System Inhibitor (RASi) Use and Atrasentan in IgAN: Post Hoc Analysis from the ALIGN Trial (KIDNEY WEEK 2025) - P3 | "These data support the potential for atrasentan to be seamlessly added onto a variety of existing RASi treatment and dose regimens. The results add to the available data for atrasentan, which has the potential to be a foundational therapy in IgAN."

Retrospective data • Glomerulonephritis • IgA Nephropathy • Renal Disease

Effect of Selective Endothelin A Receptor Antagonists on Proteinuria in IgAN: Systematic Review and Meta-Analysis (KIDNEY WEEK 2025) - "Atrasentan and SC0062 were well tolerated, with low rates of edema and no major safety signals. These results, supported by observational data, warrant further research on long-term renal outcomes and integration into treatment protocols."

Retrospective data • Review • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Nephrology • Pediatrics • Renal Disease

Baseline Characteristics of ASSIST: Phase 2 Crossover Trial of Atrasentan in Adults with IgAN on SGLT2 Inhibitors (KIDNEY WEEK 2025) - P2, P3 | "Conclusion ASSIST includes pts who remain at an increased risk of kidney failure despite maximally tolerated RASi and SGLT2i with urine protein >0.5g/d at BL. The study will provide evidence for the efficacy and safety of atrasentan in combination with SGLT2i in IgAN pts with a broad range of proteinuria levels."

Clinical • P2 data • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Renal Disease

Cancer-Induced Cardiac Dysfunction: Mechanisms, Diagnostics, and Emerging Therapeutics in the Era of Onco-Cardiology. (PubMed, Cancers (Basel)) - "Cardiac complications may arise directly from cancer itself or as adverse effects of oncologic therapies such as anthracyclines, trastuzumab, and immune checkpoint inhibitors...Current preventive and therapeutic strategies include pharmacological interventions such as ACE inhibitors, beta-blockers, statins, dexrazoxane, and endothelin receptor antagonists like atrasentan...Given the heterogeneity of cancer types and cardiovascular responses, a personalized and multidisciplinary approach is essential. Continued research and close collaboration between oncologists, cardiologists, and basic scientists will be the key to advancing care, reducing treatment-related morbidity, and ensuring that improvements in cancer survival are matched by preservation of cardiovascular health."

Journal • Review • Cachexia • Cardiovascular • Congestive Heart Failure • Heart Failure • Metabolic Disorders • Oncology • EDN1 • IL6 • TNFA