Filspari (sparsentan) / Travere Therap, Ligand, CSL Behring - LARVOL DELTA

CARI Guidelines Commentary on the KDIGO Clinical Practice Guideline for the Management of Glomerular Diseases. (PubMed, Nephrology (Carlton)) - "Our commentary underscores the need for increased participation in clinical trials to validate regional applicability and improve long-term outcomes for people with GD in Australia and New Zealand. Clinical trials of new medications have led to more treatment options that are awaiting approval."

Clinical guideline • Journal • Focal Segmental Glomerulosclerosis • Glomerulonephritis • IgA Nephropathy • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Pediatrics • Renal Disease • Vasculitis

In brief: Embryotoxicity REMS removal for endothelin receptor antagonists. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Travere Therapeutics Provides Update on FDA Advisory Committee Meeting for FILSPARI (sparsentan) in FSGS (Businesswire) - "Travere Therapeutics, Inc...announced that the U.S. Food and Drug Administration (FDA) has informed the Company that following further review of the supplemental New Drug Application (sNDA) for FILSPARI (sparsentan) in focal segmental glomerulosclerosis (FSGS), an advisory committee is no longer needed. The sNDA remains under review by the FDA with a Prescription Drug User Fee Act (PDUFA) target action date of January 13, 2026....The sNDA is supported by two of the largest and most rigorous head-to-head interventional studies conducted to date in FSGS, the Phase 3 DUPLEX Study and the Phase 2 DUET Study."

FDA event • PDUFA • Focal Segmental Glomerulosclerosis

Travere Therapeutics Announces U.S. FDA Approves REMS Modification for FILSPARI (sparsentan) in IgA Nephropathy (Yahoo Finance) - "The reduction of FILSPARI liver monitoring REMS from monthly to every three months from the onset of treatment was supported by safety data from post-marketing surveillance as well as the Phase 3 PROTECT Study in IgAN, the Phase 3 DUPLEX Study, and the Phase 2 DUET Study in focal segmental glomerulosclerosis (FSGS)."

FDA approval • IgA Nephropathy

The disordered structure of sparsentan: energy calculations for competing chain conformations. (PubMed, Acta Crystallogr C Struct Chem) - "The SST molecule displays positional disorder in three different sections. Viability tests of alternative disorder models involved the calculation of energetic contributions to analyse each possible molecular conformation within its crystal environment and identify the energetically most favourable conformations in the lattice."

Journal

Successful targeting of the alternative complement cascade with iptacopan for the treatment of IgA nephropathy: a case report. (PubMed, Swiss Med Wkly) - "To the best of our knowledge, our case report is the first in Switzerland to show that selective inhibition of the alternative complement pathway in IgA nephropathy results in significant and ongoing reduction of proteinuria after six months of therapy, supporting the innovative concept of targeting the alternative complement pathway with iptacopan to treat IgA nephropathy."

Journal • Glomerulonephritis • IgA Nephropathy • Renal Disease • CFB

Opportunities and challenges in the treatment of IgA nephropathy. (PubMed, Front Pharmacol) - "With the emerging opportunities in IgAN treatment, achieving individualized precision therapy is a key challenge currently facing research institues. This review summarizes recent advances in the treatment of IgAN and discusses possible therapeutic strategies for IgAN patients."

Journal • Review • Glomerulonephritis • IgA Nephropathy • Renal Disease

Sparsentan for Halting Renal Disease Progression in Transplant Recipients with Recurrent IgA Nephropathy (WTC 2025) - "Maintenance immunosuppression included mycophenolate mofetil, tacrolimus, and prednisone. The stability in renal function on Sparsentan proves its efficacy even in kidney transplant recipients and should be considered more frequently in cases of IgAN recurrence post-transplant."

Clinical • Acute Kidney Injury • Cardiovascular • Glomerulonephritis • Hypertension • IgA Nephropathy • Infectious Disease • Lupus Nephritis • Nephrology • Novel Coronavirus Disease • Renal Disease • Transplantation • EDN1

Sparsentan, a Novel Dual Endothelin Angiotensin Receptor Antagonists (DEARAs) for Post Transplant Proteinuria - A Single Center Outcomes Analysis (WTC 2025) - "Proteinuria in KTR is a risk factor that impacts patient and graft survival. Dual Endothelin Angiotensin receptor antagonists (DEARA) may represent a novel therapy to reduce proteinuria post Tx. Our study of Sparsentan in patients observed under a strict FDA mandated REMS protocol demonstrated a significant proteinuria reduction in most patients with over 40 % achieving complete remission."

Clinical • Post-transplantation • Cardiovascular • Glomerulonephritis • IgA Nephropathy • Renal Disease • Transplantation

Recurrent IgA Nephropathy in a Kidney Transplant Recipient Treated with Sparsentan (WTC 2025) - "IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide and is associated with a significant risk of end-stage renal disease. A common manifestation includes episodic hematuria following an upper respiratory tract infection. The degree of proteinuria has been established as the best measure of disease progression and response to treatment."

Clinical • Cardiovascular • Glomerulonephritis • Hypertension • IgA Nephropathy • Infectious Disease • Lupus Nephritis • Nephrology • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases • Transplantation

Targeted Therapy for De Novo IgA Nephropathy in a Kidney Transplant Recipient: A Case Report and Emerging Therapeutic Strategies (WTC 2025) - "This case highlights the potential of targeted therapies in treating de novo IgAN post-transplant. The combination of budesonide and sparsentan resulted in significant proteinuria reduction and stabilization of allograft function. Future research should focus on expanding on the role and benefits of these agents."

Case report • Clinical • Cardiovascular • Chronic Kidney Disease • Glomerulonephritis • Hypertension • IgA Nephropathy • Nephrology • Renal Disease • Transplant Rejection • Transplantation

Expanding the Donor Pool; Utilization of Kidneys from Donors with Lupus Nephritis - Case Report and Review of Literature (WTC 2025) - "We present our successful outcome of transplanting a kidney from a donor with Lupus related Nephrotic syndrome inducing a post Tx remission with Sparsentan therapy. Literature review of others experience like our case suggests that with careful selection - kidneys from donors with lupus nephritis can be successfully transplanted, potentially expanding the donor pool."

Case report • Clinical • Review • Atherosclerosis • Chronic Kidney Disease • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

Sparsentan in IgA nephropathy: a plain language summary of publication for the PROTECT study. (PubMed, Ther Adv Rare Dis) - "The original article reported on how well sparsentan worked to lower proteinuria and slow the worsening of kidney function (measured by estimated glomerular filtration rate (eGFR)) in people with IgA nephropathy compared with the highest possible dose of irbesartan over an approximately 2-year treatment period. The article also described the side effects that people enrolled in this study had with either sparsentan or irbesartan."

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

Safety of Drugs in Breastfeeding Women With CKD. (PubMed, Kidney Int Rep) - "Among renin-angiotensin system inhibitors, enalapril and captopril are safe for breastfeeding. Based on limited evidence, quinapril, benazepril, candesartan, and valsartan are likely acceptable for use during breastfeeding. We found no compelling human data regarding the safety of other renin-angiotensin system inhibitors or sodium-glucose cotransporter type 2 (SGLT2) inhibitors, finerenone, sparsentan, or glucagon-like peptide-1 receptor agonists (GLP1RAs) in lactation. Immunosuppressive agents, including azathioprine, cyclosporine, tacrolimus, budesonide, rituximab, and eculizumab are acceptable for use during breastfeeding. Belimumab is most likely safe; however, data are limited...No studies were found on the safety of breastfeeding while on the newer complement inhibitors, including avacopan, ravulizumab, iptacopan, and pegcetacoplan...Human lactation data on the safety of most drugs used in the treatment of CKD are limited, making evidence-based recommendations..."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Sparsentan: a dual endothelin and angiotensin II receptor antagonist approved for IgA nephropathy. (PubMed, Expert Rev Clin Pharmacol) - "As an agent that impacts the glomeruli directly, sparsentan is able to limit damage in mechanisms that previous RASi and steroids have not. Including sparsentan in the combination treatment for IgAN must be considered for adequate kidney protection."

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

Efficacy and safety of agents for IgA nephropathy: a network meta-analysis of randomized controlled trials. (PubMed, Front Med (Lausanne)) - "Clinical remission (26 RCTs included in the analysis): The CR for tonsillectomy combined with steroids pulse therapy (TSP) (RR = 8.23, 95% CI 4.11-16.45), anti-APRIL monoclonal antibody sibeprenlimab (RR = 10.00, 1.34-74.48), and steroids combined with renin-angiotensin system inhibitors (STE + RASI) (RR = 5.03, 2.61-9.68) were significantly superior to placebo. Proteinuria control (36 studies assessing 24-h UPE): The BLyS/APRIL dual-target inhibitor telitacicept (SMD = -5.21, -7.55 to -2.87) and STE + RASI (SMD = -1.98, -3.15 to -0.82) significantly reduced 24-h UPE, outperforming the mycophenolate mofetil combined with steroids regimen (SMD = -0.97, -2.74 to 0.80)...Safety (36 studies reporting adverse events): The complement inhibitor iptacopan (88.4%) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) (85.4%) had the lowest incidence of adverse events, significantly better than immunosuppressive regimens...Telitacicept, sparsentan, and TSP can be considered as..."

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

Advances in the pathophysiology and treatment of focal segmental glomerulosclerosis: The importance of a timely and tailored approach. (PubMed, World J Nephrol) - "Advances include novel biomarkers, genetic testing, and innovative therapeutics such as transient receptor potential ion channel blockers and antisense oligonucleotides for apolipoprotein 1-related FSGS. Effective management of FSGS requires a combination of timely diagnosis, evidence-based therapeutic strategies, and ongoing research to optimize patient outcomes and address gaps in the current understanding of the disease."

Journal • Chronic Kidney Disease • CNS Disorders • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Lupus Nephritis • Nephrology • Renal Disease

Clinical study outcomes in IgA nephropathy: A systematic literature review and narrative synthesis. (PubMed, PLoS One) - P3 | "Until recently, the evidence has been mixed or inconsistent across studies for the efficacy of IgAN treatments in reducing proteinuria or slowing eGFR decline due to a high risk of bias in many included studies. The latest large, phase 3 NefIgArd (NCT03643965) and PROTECT (NCT03762850) clinical trials have demonstrated a meaningful reduction in proteinuria and eGFR decline for patients with IgAN receiving targeted-release formulation budesonide (TRF-B) or sparsentan. Results from other high-quality randomized controlled trials with a follow-up period of at least 2 years are still required to better support advancements in the management of IgAN."

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

Patients With Focal Segmental Glomerulosclerosis (FSGS) Achieved Low Proteinuria Targets Earlier and More Often With Sparsentan (SPAR) vs Irbesartan (IRB) in DUPLEX (ERA 2025) - P3 | "Clinically meaningful low proteinuria thresholds and partial and complete remission definitions were achieved earlier and more often with SPAR vs IRB. In DUPLEX, the risk of KF was lower among patients who achieved partial or complete remission of proteinuria vs those who did not. Taken together, results support the nephroprotective benefit of SPAR in patients with FSGS."

Clinical • Chronic Kidney Disease • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Renal Disease

Antiproteinuric effect of SGLT2 inhibitors in non-diabetic glomerulopathies is dependent on body mass index. (ERA 2025) - "Subgroup analysis of EMPA-KIDNEY and DAPA-CKD trials done in patients with glomerular diseases [IgA Nephropathy (IgAN) and focal and segmental glomerulosclerosis (FSGS)] showed these agents are less effective in reducing proteinuria compared to other agents like Sparsentan, or Double RAS Blockade... The principal finding of the present study is the lack of significant proteinuria reduction in patients with BMI<25 kg/m², which contrasts with the significant reductions observed in overweight and obese patients. SGLT2i's main antiproteinuric mechanism of action involves reducing glomerular hyperfiltration, which is commonly seen in patients with diabetes and obesity. In non-diabetic patients with glomerulopathies, proteinuria may be sustained by mechanisms not dependent on glomerular hyperfiltration, especially in those patients with normal BMI."

Chronic Kidney Disease • Diabetic Nephropathy • Focal Segmental Glomerulosclerosis • Genetic Disorders • Glomerulonephritis • IgA Nephropathy • Metabolic Disorders • Obesity • Oncology • Renal Disease

Concomitant Sparsentan and Sodium-Glucose Cotransporter-2 Inhibitors in Adults With IgA Nephropathy in the Phase 2 SPARTACUS Trial (ERA 2025) - "Switching from RASi to SPAR treatment on a background of an SGLT2i allowed for further reduction in proteinuria in adult patients with IgAN, lowering their risk for disease progression. SPAR combined with an SGLT2i was generally well tolerated, with no unexpected safety signals"

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

Real-World Treatment Patterns of Patients with Immunoglobulin A Nephropathy (IgAN) in the United States (ERA 2025) - "Outcomes included the proportion of patients receiving IgAN therapies approved during the identification period, including renin–angiotensin–aldosterone system inhibitors (RAASi), immunosuppressants (IS), sodium-glucose cotransporter-2 inhibitors (SGLT2i), targeted-release budesonide (TRB), and sparsentan (SPAR); the proportion of patients discontinuing treatment; and treatment duration. These real-world data show that approximately two-thirds of patients with IgAN received treatment for their disease. Almost all treated patients received RAASi, and for almost half of this population, it was the only treatment received during follow-up. Use of the newer IgAN- specific therapies was low in this study population, though their approval timings relative to the study period must be considered."

Clinical • HEOR • Real-world • Real-world evidence • Fibrosis • Focal Segmental Glomerulosclerosis • Glomerulonephritis • IgA Nephropathy • Immunology • Lupus Nephritis • Renal Disease

Sparsentan reduces glomerular dysfunction and proteinuria in a rat model of serum-factor-induced nephrotic syndrome (ERA 2025) - "We have shown that the DEARA sparsentan, reduces glomerular permeability and proteinuria in a rat model of serum factor-induced podocytopathy. These findings suggest that the action of sparsentan on the GFB could help maintain barrier integrity in podocytopathic proteinuric kidney diseases."

Preclinical • Focal Segmental Glomerulosclerosis • Glomerulonephritis • IgA Nephropathy • Nephrology • Renal Disease • ALB

Effects of Sparsentan After Maximized Angiotensin Receptor Blocker (ARB) Treatment in Patients With IgA Nephropathy (IgAN) in the PROTECT Trial (ERA 2025) - "These data support the marked efficacy and tolerability of sparsentan in patients with IgAN who had previously received over 2 years of fully titrated maximum tolerated ARB therapy during the PROTECT trial."

Clinical • Glomerulonephritis • IgA Nephropathy • Renal Disease

Sparsentan reversibly decreases mesangial IgA deposition in gddY mice; a possible role for mesangial-cell -surface autoantigen expression. (ERA 2025) - "The increase in HMC-surface β2-spectrin and CBX3 expressions following incubation with ET-1 and AngII may play a role in the observation that SP900 significantly attenuated mesangial IgA deposition in gddY mice following 12 wks of treatment without alterations in sIgA or glycocalyx. Further studies are required to understand the mechanisms behind these novel findings."

Preclinical • Glomerulonephritis • IgA Nephropathy • CBX3 • EDN1