Vanrafia (atrasentan) / AbbVie, Novartis - LARVOL DELTA

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

IgA Nephropathy: An Overview of the Clinical Trials. (PubMed, Kidney Med) - "The approval of the first treatments evaluated specifically for IgAN (including delayed-release budesonide, sparsentan, atrasentan, and iptacopan) represent meaningful advancements in the management landscape, and promisingly, many more treatments seem poised to arrive. This review compiles a list of current active trials for IgAN and highlights the necessity for ongoing research to optimize therapeutic strategies to further improve outcomes for those living with IgAN."

Journal • Review • Glomerulonephritis • IgA Nephropathy • Inflammation • Renal Disease

Atrasentan: First Approval. (PubMed, Drugs) - "It has not been established whether atrasentan slows kidney function decline in patients with IgAN. This article summarizes the milestones in the development of atrasentan leading to this first approval for the reduction of proteinuria in adults with primary IgAN at risk of rapid disease progression."

Journal • Glomerulonephritis • IgA Nephropathy • Renal Disease

14,15-epoxyeicosatrienoic acid analog augments hypotensive effect of an endothelin-A receptor blocker antrasentan and prevents oedema and organ hypertrophy in spontaneously hypertensive rats. (PubMed, J Physiol Pharmacol) - "We evaluated the effectiveness of atrasentan (ATR) combined with 14,15-EET analog, EET-A, on BP, kidney function and heart morphology, and ATR-dependent oedema in conscious spontaneously hypertensive rats (SHR)...Our results suggest that addition of EET-A prolongs the hypotensive effect of ATR and prevents post-ATR water retention. Importantly, EET-A given orally, alone or combined with ATR, shows strong cardio- and renoprotective activity."

Journal • Preclinical • Cardiovascular • Hypertension • EDN1

ALIGN post-hoc analyses: Reduction in proteinuria with atrasentan across subgroups by MEST-C score, baseline hematuria and baseline UPCR (ERA 2025) - "Consistent with the primary endpoint findings, atrasentan shows favorable efficacy versus placebo in patients with IgAN regardless of baseline UPCR (<1g/g and ≥1g/g), MEST-C score, and baseline hematuria. These results add to previously presented subgroup analysis data, and further support the efficacy of atrasentan across a broad range of IgAN patients."

Retrospective data • Glomerulonephritis • IgA Nephropathy • Renal Disease

Quantifying Spillover Impacts: Effect of Novel Therapies for IgA Nephropathy on Patients Awaiting Kidney Transplant (ISPOR 2025) - "IgAN interventions included therapies with FDA approval or phase 3 proteinuria reduction results (targeted-release budesonide, sparsentan, iptacopan, dapagliflozin, and atrasentan) in addition to nonspecific IgAN therapies (including renin-angiotensin-aldosterone system inhibitors and systemic corticosteroids); the comparator was nonspecific IgAN therapies alone. IgAN interventions may provide health benefits beyond the direct clinical benefits to affected patients. These additional societal benefits should be considered when conducting value assessment of novel IgAN treatments."

Clinical • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Renal Disease • Transplantation

A Mobile App-Based Study to Evaluate Disease Burden and Treatment Patterns in Immunoglobulin A Nephropathy (IgAN) in the US (clinicaltrials.gov) - P=N/A | N=300 | Recruiting | Sponsor: Novartis Pharmaceuticals

New trial • Glomerulonephritis • IgA Nephropathy • Renal Disease

AFFINITY: Atrasentan in Patients With Proteinuric Glomerular Diseases (clinicaltrials.gov) - P2 | N=103 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jul 2026 ➔ Oct 2026

Pan tumor • Trial completion date • Diabetic Nephropathy • Focal Segmental Glomerulosclerosis • Genetic Disorders • Glomerulonephritis • IgA Nephropathy • Nephrology • Renal Disease

ASSIST: Randomized, Double-blind, Placebo-controlled, Crossover Study of Atrasentan in Subjects With IgA Nephropathy (clinicaltrials.gov) - P2 | N=54 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Glomerulonephritis • IgA Nephropathy • Renal Disease

Crosstalk Between Gastric Cancer and Adjacent Mucosa Reveals EDN1-EDNRA-Mediated Regulation of Cancer Stemness and Immunomodulation Networks. (PubMed, J Cell Mol Med) - "Conversely, pharmacological inhibition of EDNRA using ABT-627 suppressed both NCI-N87 and MKN-28 gastric cancer cells proliferation...These findings reveal a previously unidentified connection between gastric mucosa and tumour progression, positioning EDNRA not only as a molecular target, but also as a critical mediator of tissue-specific cancer communication. In conclusion, EDNRA functions as both a regulatory factor and therapeutic target, offering a promising therapeutic avenue for gastric cancer intervention."

Journal • Gastric Cancer • Immunology • Oncology • Solid Tumor • EDN1 • EDNRA

CareMed Has Been Selected as a National Specialty Pharmacy Partner for VANRAFIA (atrasentan) (GlobeNewswire) - "CareMed, an independent specialty pharmacy, is in the Limited Distribution Network for Vanrafia (atrasentan), for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) and are at risk of rapid disease progression."

Commercial • IgA Nephropathy

Novartis receives FDA accelerated approval for Vanrafia (atrasentan), the first and only selective endothelin A receptor antagonist for proteinuria reduction in primary IgA nephropathy (IgAN) (GlobeNewswire) - "Novartis...announced the US Food and Drug Administration (FDA) has granted accelerated approval for Vanrafia (atrasentan), a potent and selective endothelin A (ETA) receptor antagonist, for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression....Vanrafia was granted accelerated approval based on a prespecified interim analysis of the Phase III ALIGN study measuring the reduction of proteinuria at 36 weeks compared to placebo....The continued approval of Vanrafia may be contingent upon the verification of clinical benefit from the ongoing Phase III ALIGN study evaluating whether Vanrafia slows disease progression as measured by estimated glomerular filtration rate (eGFR) decline at week 136. The eGFR data are expected in 2026 and intended to support traditional FDA approval."

Accelerated approval • FDA approval • P3 data • IgA Nephropathy

Efficacy and safety of endothelin A receptor antagonists in IgA nephropathy: a systematic review and meta-analysis. (PubMed, Clin Kidney J) - "EARAs can significantly reduce UPCR, lower both systolic and diastolic BP, and delay eGFR decline in IgAN patients. However, they may cause anemia, cough, dizziness, hypotension, fluid retention and acute kidney injury."

Journal • Retrospective data • Acute Kidney Injury • Cough • Fibrosis • Glomerulonephritis • Hematological Disorders • Hypotension • IgA Nephropathy • Immunology • Inflammation • Lupus Nephritis • Nephrology • Renal Disease • Respiratory Diseases

Design of A Patient (pt) Platform for Real-World Data (RWD) on Iptacopan and/or Atrasentan in the United StatEs (APPRISE) for Pts With Immunoglobulin A Nephropathy (IgAN) and Complement 3 Glomerulopathy (C3G) (NKF-SCM 2025) - P3 | "Recruitment of pts with IgAN began after iptacopan approval in 2024 and will expand with future approvals. The study period will extend from treatment initiation for the first pt to end of follow-up for the last pt.Results Analyses, including of clinical characteristics and treatment patterns, adherence, and effectiveness, will be conducted continuously and refined as sample sizes become sufficient.Conclusion APPRISE will enable rapid collection of varied RWD from pts prescribed iptacopan and/or atrasentan to overcome limitations of existing RWD sources, characterize real-world disease progression and treatment patterns, and support future studies to provide valuable insights into IgAN and C3G outcomes."

Clinical • Real-world • Real-world evidence • Glomerulonephritis • IgA Nephropathy • Renal Disease

AFFINITY study: 1y results of atrasentan in IgAN in patients with UPCR <1 and ≥1g/g (NKF-SCM 2025) - P2 | "One pt discontinued treatment (tx) at Wk 13 due to an AE of headache considered tx-related. There were no tx-related serious AEs or deaths.Conclusion Atrasentan was well tolerated and resulted in a stable, clinically meaningful reduction in proteinuria over 1y of tx, comparable between pts with BL UPCR <1 and ≥1g/g."

Clinical • Glomerulonephritis • IgA Nephropathy • Nephrology • Pain • Renal Disease

ASSIST: Randomized, Double-blind, Placebo-controlled, Crossover Study of Atrasentan in Subjects With IgA Nephropathy (clinicaltrials.gov) - P2 | N=54 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals

New P2 trial • Glomerulonephritis • IgA Nephropathy • Renal Disease

Selective endothelin A receptor antagonism in chronic kidney disease: improving clinical application. (PubMed, Nephrol Dial Transplant) - "The first ERA (sparsentan) is now available for use in patients with immunoglobulin A (IgA) nephropathy, a specific type of kidney disease. Concomitant use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) may mitigate these adverse effects through their diuretic actions. The development of highly selective ETA antagonists, such as atrasentan and zibotentan, and the opportunities of combining these with SGLT2i, holds promise to optimize efficacy and safety of ERAs in clinical practice."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Fibrosis • Focal Segmental Glomerulosclerosis • Genetic Disorders • Glomerulonephritis • Heart Failure • IgA Nephropathy • Immunology • Inflammation • Metabolic Disorders • Nephrology • Obesity • Renal Disease • Type 2 Diabetes Mellitus • EDN1

ALIGN SUBGROUP ANALYSES: CLINICALLY MEANINGFUL UPCR REDUCTIONS SEEN ACROSS SUBGROUPS (ISN-WCN 2025) - "Atrasentan is a potent and selective ETA receptor antagonist...ALIGN subgroup analyses: clinically meaningful UPCR reductions seen across subgroups [Abstract FR-OR62]. Download: Download high-res image (329KB) Download: Download full-size image"

Clinical • Fibrosis • Glomerulonephritis • IgA Nephropathy • Immunology • Inflammation • Nephrology • Renal Disease