Vanrafia (atrasentan) / AbbVie, Novartis - LARVOL DELTA

Collateral Damage: IgA Nephropathy Complicating Long-Term Certolizumab Pegol Use in Crohn's Disease (ACG 2026) - "Case Description/ A 36-year-old male with CD diagnosed in 2010 (Paris classification: A2, L1, B2), underwent ileocolonic resection and was started on certolizumab pegol in 2011 after failing 5-aminosalicylic acid, 6-mercaptopurine, and infliximab therapy...Certolizumab pegol was stopped and CD treatment with vedolizumab was started. Treatment with corticosteroids, mycophenolate, losartan, and atrasentan was initiated...Targeted budesonide was not a treatment option in this case given prior bowel resection, which emphasizes a treatment consideration unique to CD patients. This case emphasizes the importance of routine renal monitoring in patients on long-term anti-TNF therapy. Figure: Light microscopy (PAS stain) demonstrating mesangial hypercellularity Figure: Immunofluorescence microscopy demonstrating diffuse mesangial IgA deposits"

Crohn's disease • Gastroenterology • Glomerulonephritis • IgA Nephropathy • Immunology • Inflammation • Inflammatory Bowel Disease • Nephrology • Renal Disease

Endothelin Receptor Antagonists in Resistant Hypertension and Proteinuric Kidney Disease: Receptor Strategy and Volume Management. (PubMed, J Clin Hypertens (Greenwich)) - "Aprocitentan is the first and only ERA approved for hypertension; in PRECISION, the approved 12.5-mg once-daily dose reduced placebo-corrected 24-h ambulatory systolic blood pressure by 4.2 mm Hg, with reductions of 4.2 to 5.9 mm Hg across the studied doses. In IgA nephropathy (IgAN), sparsentan reduces proteinuria and slows estimated glomerular filtration rate (eGFR) decline. Atrasentan has an established antiproteinuric effect and a favorable eGFR slope, although the prespecified week-136 eGFR contrast in the final ALIGN analysis did not reach statistical significance. Zibotentan plus dapagliflozin remains investigational. Across these settings, successful ERA use depends on careful patient selection, indication-specific interpretation of the evidence, optimized diuretic and cardiorenal therapy, and early surveillance for edema, anemia, liver-test abnormalities, and pregnancy risk, with treatment interruption or discontinuation when clinically significant..."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Glomerulonephritis • Hematological Disorders • Hypertension • IgA Nephropathy • Nephrology • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases

A-MECH: Mechanistic Evaluation of Atrasentan in Patients With IgA Nephropathy (IgAN) (clinicaltrials.gov) - P4 | N=20 | Not yet recruiting | Sponsor: University of Illinois at Chicago

New P4 trial • Glomerulonephritis • IgA Nephropathy • Renal Disease

Next-generation therapeutics and renaissance of legacy drugs targeting the endothelin system. (PubMed, Can J Physiol Pharmacol) - "Endothelin-1 (ET-1) was discovered in 1988, followed by identification of ETA and ETB receptors in 1990, enabling rapid development of the first endothelin receptor antagonists (bosentan, ambrisentan, and macitentan) for pulmonary arterial hypertension, a condition marked by elevated ET-1. Nearly a decade later, a new therapeutic wave began with the ETB agonist sovateltide (2021) for cerebral ischemic stroke, demonstrating the benefits of ETB activation...Clazosentan (ETA) for cerebral vasospasm and aprocitentan (ETA/ETB) for resistant hypertension extended endothelin-targeted therapy into more common diseases. In kidney disease, sparsentan (AT1/ETA) and atrasentan (ETA) have both been approved for IgA nephropathy, with atrasentan succeeding after earlier failed trials...This review outlines approaches for identifying legacy endothelin compounds suitable for new indications, using zibotentan, now combined with dapagliflozin to reduce fluid retention as an example. Kidney..."

Journal • Review • Cardiovascular • Glomerulonephritis • Hypertension • IgA Nephropathy • Ischemic stroke • Nephrology • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases • EDN1

EDNRA Forms a Positive Feedback Loop with the Hippo/YAP Axis to Drive Triple-Negative Breast Cancer Progression. (PubMed, Adv Sci (Weinh)) - "Atrasentan also sensitized TNBC cells to paclitaxel and produced positive zero interaction potency (ZIP) synergy scores. EDNRA establishes a druggable positive feedback loop with Hippo/YAP signaling and represents a potential therapeutic vulnerability in YAP-driven TNBC."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CTGF • EDN1 • EDNRA • TEAD4

Sibeprenlimab (Voyxact) for primary immunoglobulin A nephropathy. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Glomerulonephritis • IgA Nephropathy • Renal Disease

Approved therapies in the IgA nephropathy armamentarium: a summary of the evidence. (PubMed, Kidney Int Suppl (2011)) - "Recent approvals include Nefecon, sparsentan, iptacopan, atrasentan, and sibeprenlimab. Nefecon, a targeted-release formulation of budesonide, is the only US Food and Drug Administration and European Medicines Agency fully approved agent that is designed to target the primary source of IgAN: galactose-deficient IgA1 production in the gut mucosa...Sparsentan demonstrated a significant reduction in proteinuria and estimated glomerular filtration rate decline compared with irbesartan...The endothelin A receptor antagonist atrasentan and A proliferation binding ligand inhibitor sibeprenlimab have also received accelerated US Food and Drug Administration approval, based on interim phase 3 results showing significant proteinuria reduction versus placebo in patients with IgAN. This expanded clinical armamentarium offers clinicians and patients greater choice and improved disease control in IgAN management."

Journal • Review • Fibrosis • Glomerulonephritis • IgA Nephropathy • Immunology • Inflammation • Renal Disease • CFB

Management of IgA nephropathy and the expanding role of immunomodulation. (PubMed, Kidney Int Suppl (2011)) - "Targeted therapies, such as Nefecon (targeted-release formulation budesonide) and iptacopan, which address the immune-mediated pathogenic triggers of nephron loss, are important additions. Lifestyle modification, renin-angiotensin system inhibition, sodium-glucose cotransporter-2 inhibitors, and newer agents, such as sparsentan and atrasentan, are also available to manage the generic responses to IgAN-induced nephron loss common to many forms of proteinuric chronic kidney disease. As our understanding of the pathogenic mechanisms underlying disease progression in IgAN has expanded, so has the recognition that IgAN-specific, targeted immunomodulatory therapies are needed, and that these can be used in combination with other agents addressing the more generic causes of nephron loss. These approaches together can help to modify the course of the disease in patients and avoid progression to kidney failure."

Journal • Review • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Immunology • Nephrology • Renal Disease

IgA nephropathy management: what does the future hold? (PubMed, Kidney Int Suppl (2011)) - "Two agents have been fully approved for use in patients with IgAN in some regions: Nefecon, an oral targeted-release formulation of budesonide, and sparsentan, a dual endothelin A and angiotensin II receptor antagonist. Iptacopan and atrasentan are conditionally approved on the basis of proteinuria data; full approval will be evaluated once data on kidney function are available...Combination therapies with different classes of drugs will likely become the new standard of care for chronic kidney disease as they target distinct pathogenic mechanisms or "hits" (namely, hemodynamic, immune, galactose-deficient IgA1-generating, inflammatory, and fibrotic processes involved in IgAN and chronic kidney disease progression). To improve personalized care for patients with IgAN, further research is needed to identify and validate noninvasive biomarkers for diagnosis, prognosis, treatment selection, and monitoring response."

Journal • Review • Chronic Kidney Disease • Fibrosis • Glomerulonephritis • IgA Nephropathy • Nephrology • Renal Disease

Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN (clinicaltrials.gov) - P3 | N=28 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Glomerulonephritis • IgA Nephropathy • Nephrology • Pediatrics • Renal Disease

Improving the Cardiorenal Usability of Endothelin Receptor Antagonism in Albuminuric Chronic Kidney Disease: A Testable Role for SGLT2 Inhibitor-based Mitigation of Fluid Retention. (PubMed, Cardiovasc Drugs Ther) - "Combined ERA/SGLT2i therapy should be viewed as a mechanistically plausible and clinically testable positioning strategy, not an established treatment paradigm. Broader adoption requires confirmation of durable kidney benefit, cardiovascular safety, real-world feasibility, and reproducible tolerability across eGFR strata and congestion-prone CKD phenotypes."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

Characterization of Atrasentan Metabolic Pathway in Human Liver Microsomes Using Feature-Based Molecular Networking. (PubMed, Pharmaceutics) - "However, its direct translation to in vivo oxidative stress or covalent protein binding requires further studies. These findings demonstrate that feature-based molecular networking is a valuable strategy for metabolite characterization, underscoring the urgent need for further in vivo metabolism studies to definitively assess hepatotoxic risks associated with these reactive metabolites."

Journal • Chronic Kidney Disease • Diabetic Nephropathy • Glomerulonephritis • Hepatology • IgA Nephropathy • Liver Failure • Nephrology • Renal Disease

Long-term kidney protection in IgA nephropathy with atrasentan. (PubMed, Nat Rev Nephrol) - No abstract available

Journal • Glomerulonephritis • IgA Nephropathy • Renal Disease

Atrasentan: new molecule in the therapy of IgA nephropathy and other glomerulopathies. (PubMed, Ceska Slov Farm) - "Current studies confirm its benefit in reducing proteinuria. In combination with currently used renoprotective drugs, atrasentan may significantly contribute to reducing renal damage and thus slowing the progression of chronic kidney disease."

Journal • Review • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Nephrology • Renal Disease

Efficacy of telitacicept and nefecon in the treatment of IgA nephropathy supported by histologic evidence (ERA 2026) - "Introduction Novel agents like telitacicept (a BAFF/APRIL inhibitor) and nefecon (targeted-release formulation of budesonide) offer new therapeutic avenues for IgAN...By January 2024, following a 4-month regimen of prednisone 50 mg qd and mycophenolate mofetil (MMF) 0.75 g q12h, sCr decreased to 154 μmol/L and proteinuria reduced to 3.7 g/d...Therapy was then adjusted to telitacicept 160 mg qw plus atrasentan, with ongoing follow-up...Why this case is exeptional This case demonstrates the successful use of two mechanistically distinct novel therapies and provides a treatment optimization strategy for progressive IgAN. Image The patient's kidney pathological features and lab values."

Clinical • Glomerulonephritis • IgA Nephropathy • Renal Disease

Efficacy and safety of atrasentan treatment in participants with IgA nephropathy: 2.5-year eGFR results from the ALIGN trial (ERA 2026) - "Atrasentan was well tolerated with a safety profile consistent with previous reports. Image"

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

Atrasentan for the Management of Refractory Proteinuria in IgA Nephropathy: A Case Report (ERA 2026) - "Based on benefit–risk assessment, systemic glucocorticoids or targeted-release budesonide (Nefecon) may be added to address disease-specific pathogenic drivers...She was treated with guideline- recommended optimized supportive therapy, including glucocorticoids (prednisone 0.5 mg/kg/day), mycophenolate mofetil, an SGLT2 inhibitor (dapagliflozin 10 mg/day), an angiotensin receptor blocker (losartan potassium 50 mg/day), and hydroxychloroquine...Why this case is exeptional This case illustrates a real-world therapeutic dilemma in IgA nephropathy, where persistent high-risk proteinuria could not be adequately controlled due to intolerance to immunosuppressive therapy and limited up-titration of RAS inhibition. The rapid and substantial antiproteinuric response to atrasentan provides real-world evidence supporting ETA receptor antagonism as a viable treatment option beyond guideline-recommended supportive care."

Case report • Clinical • Chronic Kidney Disease • Glomerulonephritis • Hypotension • IgA Nephropathy • Infectious Disease • Inflammation • Renal Disease • Respiratory Diseases

Update on the Characteristics of Patients With Immunoglobulin A Nephropathy (IgAN) Receiving Iptacopan and Atrasentan: APPRISE-IgAN Data Platform (ERA 2026) - "As part of the study design, e xperience with IgAN-specific therapy was defined as prior treatment with ACEi /ARBs and/or SGLT2i , and included the branded therapies budesonide, sparsentan , iptacopan, and/or atrasentan. Ongoing APPRISE-IgAN recruitment and data collection will provide further valuable insights into th ese population s over time . Image"

Clinical • Glomerulonephritis • IgA Nephropathy • Renal Disease

Atrasentan in patients with IgA nephropathy (ALIGN): final 2·5-year results from a randomised, double-blind, placebo-controlled, phase 3 trial. (PubMed, Lancet) - P3 | "Atrasentan reduced proteinuria and preserved kidney function after 2·5 years. This effect was present with or without concomitant SGLT2 inhibitor use. Atrasentan was well tolerated."

Journal • P3 data • Glomerulonephritis • IgA Nephropathy • Renal Disease

ALIGN: Atrasentan in Patients With IgA Nephropathy (clinicaltrials.gov) - P3 | N=404 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Dec 2026 ➔ Apr 2028 | Trial primary completion date: Dec 2026 ➔ Apr 2028

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

Novartis IgAN data in The Lancet show clinically meaningful slowing of kidney function decline with Vanrafia over 2.5 years (Novartis Press Release) - "Phase III ALIGN study results showed reduced rate of kidney function decline by ~34% with Vanrafia vs placebo, based on supportive eGFR slope analysis; Vanrafia reduced protein in urine by 38.3% vs placebo at 9 months, with reductions sustained through end of treatment; Patients additionally receiving background SGLT2 inhibitors also consistently showed slower kidney function decline with Vanrafia vs placebo"

P3 data • IgA Nephropathy

Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN (clinicaltrials.gov) - P3 | N=28 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jan 2031 ➔ Dec 2032 | Trial primary completion date: Nov 2030 ➔ Sep 2031

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

Progress in mechanistic and clinical translational research of endothelin A receptor antagonists in the treatment of diabetic kidney disease: a narrative review. (PubMed, Front Endocrinol (Lausanne)) - "In clinical settings, the SONAR trial showed that atrasentan significantly reduced the risk of renal events (hazard ratio ~0.65) and achieved approximately 30-40% reduction in urinary albumin-to-creatinine ratio (UACR) in selected responders...ETA receptor antagonists represent a promising mechanism-based adjunctive therapy for DKD. Their future role is likely to be integrated within combination regimens alongside SGLT2 inhibitors and MRAs, guided by biomarker-driven precision medicine approaches to optimize efficacy while minimizing adverse effects."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetic Nephropathy • Fibrosis • Heart Failure • Hypertension • Immunology • Inflammation • Nephrology • Renal Disease • EDN1

Novartis will present data from 15 abstracts from its kidney portfolio at this year’s European Renal Association (ERA) Congress in Glasgow, June 3-6. (The Manila Times)

Clinical protocol • P1/2 data • P3 data • Autosomal Dominant Polycystic Kidney Disease • IgA Nephropathy

New and Emerging Nonimmunosuppressive Drug Therapies for Primary Adult Glomerular Diseases. (PubMed, Kidney Med) - "Given the safety concerns associated with immunosuppressive therapies, we discuss the future role of newer nonimmunosuppressive agents including finerenone (a nonsteroidal mineralocorticoid receptor antagonist), sparsentan (a dual endothelin-angiotensin II receptor antagonist), atrasentan (an endothelin receptor antagonist), and iptacopan (complement inhibitor), which are currently Food and Drug Administration approved or are under investigation in clinical trials for primary GDs. Our review focuses on nonimmunosuppressive drugs for GD. We consider nonimmunosuppressive drugs already available for treating GD, ones that have only recently been made available, and drugs that are being tested in large clinical trials involving people with GD."

Journal • Review • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Hypertension • IgA Nephropathy • Nephrology • Renal Disease