Vanrafia (atrasentan) / AbbVie, Novartis - LARVOL DELTA

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

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

ALIGN post-hoc analyses: Reduction in proteinuria with atrasentan across subgroups by MEST-C score, baseline hematuria and baseline UPCR (ERA 2025) - No abstract available

Retrospective data • 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

AFFINITY study: 1-year results of atrasentan in IgA nephropathy (IgAN) (ISN-WCN 2025) - P3 | "The ongoing global Phase 3 ALIGN study (NCT04573478) is evaluating the effect of atrasentan on proteinuria and kidney function in patients with IgAN. This abstract was also submitted for the ASN Kidney Week 2024: Barratt J, et al.: AFFINITY study: 1-year results of atrasentan in IgA nephropathy (IgAN) [Abstract FR-PO855]."

Glomerulonephritis • IgA Nephropathy • Pain • Renal Disease

QUANTITATIVE IMAGE ANALYSIS UNCOVERS THE EFFICACY OF THE SELECTIVE ENDOTHELIN A RECEPTOR ANTAGONIST ATRASENTAN IN A RAT MODEL OF IGA NEPHROPATHY (ISN-WCN 2025) - "This experimental setting will help evaluating the efficacy of drugs targeting IgA nephropathy. The content of this abstract has been submitted to ASN Kidney Week 2024."

Preclinical • Glomerulonephritis • IgA Nephropathy • Inflammation • Lupus Nephritis • Renal Disease • CST3 • KIM1 • THY1

Study Design and Baseline Characteristics of ALIGN, a Randomized Controlled Study of Atrasentan in Patients With IgA Nephropathy. (PubMed, Kidney Int Rep) - P3 | "At baseline in the main stratum, mean age was 44.7 years, 42.4% were female, mean eGFR and median UPCR were 58.9 ml/min per 1.73 m2 and 1.4 g/g, respectively. The ongoing ALIGN trial evaluates the efficacy and safety of atrasentan in a representative global IgAN population at risk for disease progression despite optimized RAS inhibitor therapy and includes an exploratory stratum evaluating atrasentan use in combination with an SGLT2i."

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

ALIGNing the treatment of IgA nephropathy: Reducing proteinuria with endothelin A receptor inhibition. (PubMed, Med) - "The ALIGN trial1 demonstrates that atrasentan, an endothelin A (ETA) receptor antagonist, reduces proteinuria in patients with IgA nephropathy (IgAN), a key goal to slow progressive renal disease. These results are consistent with those from sparsentan,2,3 a combined ETA and angiotensin inhibitor, in IgAN, suggesting two-year data will show atrasentan improves renal outcomes."

Journal • Glomerulonephritis • IgA Nephropathy • Nephrology • Renal Disease

Endothelin receptor antagonists in chronic kidney disease. (PubMed, Nat Rev Nephrol) - "In patients with type 2 diabetes and CKD, the selective ETA ERA, atrasentan, reduced albuminuria and kidney function decline...Moreover, combined administration of a low dose of the ETA-selective ERA, zibotentan, with the sodium-glucose cotransporter 2 (SGLT2) inhibitor, dapagliflozin, enhanced albuminuria reduction and mitigated fluid retention in patients with CKD. Notably, sparsentan and aprocitentan have received FDA approval for the treatment of IgA nephropathy and treatment-resistant hypertension, respectively. This Review describes our current understanding of the use of ERAs in patients with CKD to guide their optimal safe and effective use in clinical practice."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Glomerulonephritis • Heart Failure • Hypertension • IgA Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • EDN1

Sex differences in response to the endothelin receptor antagonist atrasentan in individuals with type 2 diabetes and chronic kidney disease: a post hoc analysis of the SONAR trial. (PubMed, Diabetologia) - P3 | "Atrasentan showed greater kidney protection in female than in male participants but also induced more heart failure events in the female participants. These data suggest that sex-specific dosing regimens may be considered to optimise ERA treatment."

Journal • Retrospective data • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Heart Failure • Metabolic Disorders • Nephrology • Renal Disease • Transplantation • Type 2 Diabetes Mellitus

Effects of Cacna1d D307G mutation on blood pressure and kidney function in rats with salt loading. (PubMed, Kidney Blood Press Res) - "Activation of ET-1/ETA system in D307G mutation rats might contributed to increased sensitivity to salt loading, augmented hypertension, and exacerbated the renal injury."

Journal • Preclinical • Cardiovascular • Fibrosis • Hypertension • Immunology • Inflammation • Renal Disease • KIM1

Urinary Clusterin as a Pharmacodynamic Response Biomarker for the Endothelin Receptor Antagonist Atrasentan (KIDNEY WEEK 2024) - "Our study identified and validated uCLU as a promising pharmacodynamic biomarker for assessing treatment response to atrasentan. This calls for further clinical evaluation and implementation, and fosters indivdualized treatment through molecular stratification."

Biomarker • PK/PD data • Chronic Kidney Disease • Diabetic Nephropathy • Nephrology • Renal Disease • CLU • EDN1

AFFINITY Study: 1-Year Results of Atrasentan in IgA Nephropathy (KIDNEY WEEK 2024) - P3 | "Atrasentan, in addition to standard of care, was well tolerated and resulted in a clinically meaningful, stable reduction in proteinuria over 1 year of treatment, supporting its therapeutic potential in IgAN. The ongoing global Phase 3 ALIGN study (NCT04573478) is evaluating the effect of atrasentan on proteinuria and kidney function in pts with IgAN."

Glomerulonephritis • IgA Nephropathy • Pain • Renal Disease

Atrasentan in Patients with IgA Nephropathy. (PubMed, N Engl J Med) - P3 | "In this prespecified interim analysis, atrasentan resulted in a significant and clinically meaningful reduction in proteinuria as compared with placebo in patients with IgA nephropathy. (Funded by Novartis; ALIGN ClinicalTrials.gov number, NCT04573478.)."

Journal • Cardiovascular • Congestive Heart Failure • Glomerulonephritis • Heart Failure • IgA Nephropathy • Renal Disease

The effect of the endothelin receptor antagonist atrasentan on insulin resistance in phenotypic clusters of patients with type 2 diabetes and chronic kidney disease. (PubMed, Diabetes Obes Metab) - "Atrasentan significantly improved insulin sensitivity in patients with T2D and CKD, especially in those characterized by high insulin resistance (SIRD cluster). Further studies are warranted to investigate the long-term clinical outcomes of atrasentan treatment in these distinct phenotypic clusters."

Journal • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Genetic Disorders • Metabolic Disorders • Nephrology • Obesity • Renal Disease • Type 2 Diabetes Mellitus