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

Case Report: Maximizing the anti-proteinuric response: a multicenter real-world sparsentan case series in IgA disorders. (PubMed, Front Nephrol) - "We present a case series featuring seven patients - five diagnosed with IgAN and two with IgA vasculitis (IgAV) - with severe proteinuria who were treated with Sparsentan, sometimes in combination with other medications such as targeted-release formulation (TRF) budesonide, sodium-glucose cotransporter-2 (SGLT2) inhibitors, or mycophenolate. Sparsentan was well-tolerated overall, with no significant hyperkalemia or hepatotoxicity reported in this group. These cases emphasize the real-world experience, promising efficacy and safety of Sparsentan in reducing proteinuria in patients with IgA-mediated glomerular disorders, including its application in combination therapies and patients with concurrent or prior immunosuppression."

Journal • Real-world evidence • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Renal Disease • Vasculitis

Treatment of Recurrent IgA Nephropathy After Kidney Transplantation: Case Report and Comprehensive Literature Review. (PubMed, Clin Case Rep) - "Recurrent IgA nephropathy after kidney transplantation remains a major cause of graft dysfunction. This case highlights successful management with targeted-release budesonide combined with sparsentan, underscoring the importance of early recognition and the promise of emerging therapies to preserve long-term allograft function."

Journal • Glomerulonephritis • IgA Nephropathy • Renal Disease • Transplantation

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

Matching-adjusted indirect comparison of kidney function in patients with immunoglobulin A nephropathy treated with nefecon or sparsentan. (PubMed, J Comp Eff Res) - P3 | "Aim: We compared the effects of nefecon, an oral targeted-release budesonide formulation, and sparsentan, an oral, dual endothelin-angiotensin receptor antagonist, on estimated glomerular filtration rate (eGFR) in patients with immunoglobulin A nephropathy, a leading cause of chronic kidney disease. Materials & We conducted an anchored matching-adjusted indirect comparison (MAIC) using patient-level data from NefIgArd (NCT03643965; n = 364), a randomized (1:1) trial of nefecon plus optimized renin-angiotensin system inhibitor (RASi) therapy versus placebo plus RASi; and aggregate data from PROTECT (NCT03762850; n = 404), a randomized (1:1) trial of sparsentan versus irbesartan, an angiotensin receptor blocker...Sensitivity analysis results were consistent with the main findings. In patients with immunoglobulin A nephropathy, nefecon plus optimized RASi may preserve kidney function to a greater extent than sparsentan."

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

Effect of Sequential Targeted-Release Formulation (TRF)-Budesonide and Sparsentan Therapy in a Patient with IgAN: Can Histopathology Predict Therapeutic Response? (KIDNEY WEEK 2025) - "He was treated with Losartan 100 mg a day and Lisinopril 20 mg twice a day for many years In 2021, his UPC ratio was 2.4-3 mg/mg. He was started on Empagliflozin in July 2021 and Lisinopril decreased to 20 mg a day...The new guidelines have distinguished this and can help guide appropriate effective therapies based on histological variables. Improvement of UPCR with supportive therapies"

Clinical • Glomerulonephritis • IgA Nephropathy • Renal Disease

Patients (Pts) with FSGS Reach Proteinuria <0.7 g/g More Often with Sparsentan (SPAR) vs. Irbesartan (IRB) in DUPLEX: Implications for Kidney Failure (KF) Risk (KIDNEY WEEK 2025) - P3 | "Conclusion In DUPLEX, pts with FSGS achieved UPCR <0.7 g/g earlier and more often with SPAR vs IRB. Together, clinical trial and real-world data indicate that reaching UPCR <0.7 g/g is associated with clinically meaningful reductions in KF risk both in the near- and long-term, supporting the long-term benefit of SPAR’s anti-proteinuric effect."

Clinical • Late-breaking abstract • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Renal Disease

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

Baseline Characteristics and Treatment Satisfaction of Patients (Pts) Enrolled in IgAN Bridge: Interim Results from a Home-Reported Outcomes (HROs) Study (KIDNEY WEEK 2025) - "The most common treatments selected included sparsentan (18%), fish oil (18%), and empagliflozin (14%). Pts with lower treatment satisfaction had greater symptom severity, and fatigue was the most frequently tracked symptom across satisfaction levels. This heterogeneity highlights the need to understand the diverse experiences and symptom burden of pts with IgAN."

Clinical • Fatigue • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology

Therapies for IgAN in the Cure Glomerulonephropathy Network (CureGN) (KIDNEY WEEK 2025) - "Few participants (n=5) received newer IgAN therapies (eg, sparsentan, targeted delayed-release budesonide)...Conclusion The impact of traditional IST on long term kidney function requires further exploration. Despite availability of novel IgAN therapies, conservative management (RAS inhibition, SGLT2i) and traditional IST remain most used."

Glomerulonephritis • IgA Nephropathy • Renal Disease

Safety Profile of Combined Nefecon and Sparsentan Therapy (KIDNEY WEEK 2025) - "Our findings show that compared to monotherapy, combined use of Nefecon and sparsentan reduces the spectrum of AEs. Table 1 *denotes previously reported."

Clinical • Glomerulonephritis • IgA Nephropathy

Real-World Treatment Patterns of Patients (Pts) with Glomerular Inflammation in IgAN (KIDNEY WEEK 2025) - "Outcomes included proportion on IgAN therapies (renin–angiotensin–aldosterone system inhibitors [RAASi], sodium-glucose cotransporter-2 inhibitors [SGLT2i], immunosuppressants [IS, corticosteroids/glucocorticoids/MMF], targeted-release budesonide [TRB], and sparsentan [SPAR]); treatment sequencing (lines of therapy [LOTs]); and steroid-related adverse events (AEs) in pts with ≥1 IS/TRB claim...Conclusion In this real-world study, many pts with IgAN had glomerular inflammation. In this population, steroid-related AEs and high LOT discontinuation rates highlight the need for additional therapies and better matching of pts to treatments."

Clinical • HEOR • Real-world • Real-world evidence • Glomerulonephritis • IgA Nephropathy • Inflammation • Lupus Nephritis • Nephrology • Renal Disease

First Long-Term Real-World Evidence of Sparsentan Efficacy in Patients with IgAN Treated with SGLT2 Inhibitors (KIDNEY WEEK 2025) - "Conclusion In the extended follow-up of our real-world data subset we could confirm initial findings that sparsentan offers a significant and sustained antiproteinuric effect even in patients already receiving SGLT2 inhibitors. Course of proteinuria (UPCR) under therapy with sparsentan."

Clinical • HEOR • Real-world • Real-world evidence • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Renal Disease

Real-World Data on Low Proteinuria with Sparsentan (SPAR) in Patients (Pts) with IgAN: A Case Series (KIDNEY WEEK 2025) - "In PROTECT, SPAR was well tolerated (95% of pts received the target dose [400 mg/d]) and lowered proteinuria, leading to complete remission (CR) of proteinuria more often vs maximum labeled dose irbesartan. In 3 pts with intolerance to the 400-mg/d dose, dose modification (200 mg/d or alternating 200 mg/400 mg every other day) was well tolerated, with effective proteinuria control (UPCR <0.5 g/g). Discussion This case series supports the benefit of SPAR, alone or in combination with other txs, on achieving clinically meaningful low proteinuria thresholds, including CR, with real-world use in pts with IgAN."

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

More than Skin Deep: Successful Management of Rare IgA Vasculitis with Kidney Involvement (KIDNEY WEEK 2025) - "Diagnosed with IgAV with IgA dominant glomerulonephritis, she was started on prednisone, mycophenolate mofetil (MMF), and lisinopril. RAAS blockade, corticosteroids and cyclophosphamide or MMF are mainstay of treatment, but newer drugs like sparsentan and iptacopan, specifically targeting the immune system, have shown promise. From left to right: Gross specimen minimal interstitial fibrosis, IF granular mesangial IgA deposition, LM IgA-dominant mesangial deposits with mesangial hypercellularity and crescent."

Fatigue • Fibrosis • Glomerulonephritis • IgA Nephropathy • Immunology • Lupus Nephritis • Musculoskeletal Pain • Nephrology • Renal Disease • Vasculitis

Case Series of Proteinuria Reduction with Sparsentan (SPAR) Combined with SGLT2 Inhibitors (SGLT2is) in Adults with IgAN at a Single Site (KIDNEY WEEK 2025) - "Discussion These cases show real-world experience of proteinuria reduction when SPAR is used with SGLT2i treatment in adults with IgAN, even in patients who previously tried immunosuppressive therapy or ARB standard of care. SPAR+SGLT2i was generally well-tolerated with no new safety signals."

Clinical • Glomerulonephritis • IgA Nephropathy • Renal Disease

An Atypical Case of IgAN with Chronic Daily Macroscopic Hematuria for 10 Years (KIDNEY WEEK 2025) - "He is in the process of obtaining sparsentan for further therapy...It is presently not directly implemented in the risk score but is said to correlate with the Oxford MEST system. Most treatments are tailored towards proteinuria management and data is sparse on the best approach to treatment in patients with persistent hematuria."

Clinical • Anemia • Fibrosis • Gastrointestinal Disorder • Glomerulonephritis • Hematological Disorders • IgA Nephropathy • Immunology • Nephrology • Otorhinolaryngology • Renal Disease

Impact of Histology on Efficacy of Sparsentan Therapy in IgAN: Central Biopsy Review of Patients in the PROTECT Trial (KIDNEY WEEK 2025) - "Background In PROTECT, sparsentan (SPAR), a non-immunosuppressive, dual endothelin angiotensin receptor antagonist, resulted in significant reduction in proteinuria and preservation of kidney function when compared to irbesartan (IRB) in adults with IgA nephropathy. The % tubular atrophy/interstitial fibrosis and % of glomeruli showing segmental sclerosis showed a significant negative correlation with BL eGFR whilst % of glomeruli showing endocapillary hypercellularity positively correlated with BL eGFR. The reduction in proteinuria at 36 weeks in pts treated with SPAR (n=47) was consistent across MEST-C scores or continuous histological data; pts showed treatment benefit in all groups (Fig 1) Conclusion Whilst histological features are associated with baseline eGFR and proteinuria, the therapeutic efficacy of SPAR is independent of biopsy findings, including the Oxford Classification MEST-C scores."

Biopsy • Clinical • Review • Fibrosis • Glomerulonephritis • IgA Nephropathy • Immunology • Renal Disease

Estimating the Benefits of Proteinuria Reduction on Kidney Failure Risk in the DUPLEX Study Using an Aligned FSGS Cohort from the UK RaDaR Registry (KIDNEY WEEK 2025) - "This work quantifies the likely benefits of proteinuria reduction observed in the DUPLEX study of sparsentan (SPAR) on risk of KF events, by extracting a cohort from RaDaR aligned to the DUPLEX population...Applied to DUPLEX, where a 26% relative UPCR reduction was observed, the model predicts a HR of 0.77 (95% CI 0.70-0.85) (SPAR vs irbesartan) for KF risk. Conclusion Analysis of the DUPLEX-aligned RaDaR cohort is consistent with PARASOL findings and predicts a significant and clinically meaningful benefit in 84-month kidney survival for the relative reductions in UPCR observed with SPAR in DUPLEX. These results are corroborated by lower KF event rates seen in the SPAR arm of DUPLEX."

Focal Segmental Glomerulosclerosis • Glomerulonephritis • Renal Disease

Sparsentan Ameliorates Proteinuria in Children with Glomerular Diseases (KIDNEY WEEK 2025) - "Prior to the start of Sparsentan, the patients were stopped from taking angiotensin-converting-enzyme inhibitor (ACEi), angiotensin II receptor blockers (ARB), finerenone and dapagliflozin. No one had oedema. Conclusion Significant reductions in proteinuria were observed in children with glomerular diseases, even after 3-4 weeks of treatment with sparsentan."

Clinical • Genetic Disorders • Glomerulonephritis • Nephrology • Renal Disease

Sparsentan (SPAR) vs. Irbesartan (IRB) in Pediatric Patients with FSGS in the Phase 3 DUPLEX Trial (KIDNEY WEEK 2025) - P3 | "SPAR had a safety profile that was comparable to IRB; no pts in the SPAR arm and 2 pts in the IRB arm discontinued treatment due to adverse events ( Table ). Conclusion Consistent with findings in the overall DUPLEX population, SPAR was well tolerated and led to rapid and sustained proteinuria reductions vs maximum labeled dose IRB in pediatric pts with FSGS."

Clinical • P3 data • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Pediatrics • Renal Disease

Real-World Treatment for IgAN in the Veterans Health Administration (KIDNEY WEEK 2025) - "IgAN treatments, including systemic glucocorticoids (SGC), other immunosuppressants (azathioprine, mycophenolate, or cyclophosphamide), angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), sodium-glucose co-transporter 2 inhibitors (SGLT2i), and novel treatments (iptacopan, sparsentan, targeted delayed-release budesonide) were ascertained using pharmacy records and categorized as continued use at IgAN diagnosis, incident use at IgAN diagnosis, discontinued use after IgAN diagnosis, or no use...Conclusion Low rates of existing and novel treatment use in this cohort reveal an opportunity to improve adherence to draft updates to IgAN guidelines that suggest using immunomodulating agents concurrently with supportive therapies such as ACEi/ARBs and SGLT2is. Many people discontinued treatments, suggesting a possible role for novel therapies as alternative options."

Clinical • HEOR • Real-world • Real-world evidence • Ankylosing Spondylitis • Chronic Kidney Disease • Dermatitis • Dermatology • Glomerulonephritis • Hepatitis B • Hepatitis C • Hepatology • Human Immunodeficiency Virus • IgA Nephropathy • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Renal Disease • Rheumatology • Seronegative Spondyloarthropathies

Real-World Experience with Targeted-Release Budesonide in the Treatment of IgAN (KIDNEY WEEK 2025) - "At the initiation of Tarpeyo, ten patients were receiving renin-angiotensin-aldosterone system (RAAS) inhibitors, including three patients on sparsentan. No serious infections were reported during the treatment period. Conclusion At our center, Tarpeyo produced outcomes comparable to those observed in the Phase III NefIgArd trial, with a significant reduction in proteinuria and an acceptable safety and tolerability profile."

Clinical • Real-world • Real-world evidence • Acne Vulgaris • Cardiovascular • Glomerulonephritis • Hypertension • IgA Nephropathy • Infectious Disease • Lupus Nephritis • Nephrology • Renal Disease

Sparsentan Slows the Loss of Kidney Function in Patients with IgAN: Post Hoc Analyses of the Phase 3 PROTECT Study (KIDNEY WEEK 2025) - "This post -hoc analysis compares the efficacy of SPAR vs. irbesartan (IRB) in preventing the progression to chronic kidney disease (CKD) stages 4 or 5 and was conducted as part of the HTA process in Germany. Statistically significantly fewer patients progress to CKD stages 4 or 5 under SPAR, and the time to reach CKD stages 4 or 5 is prolonged —an effect outcome that was accepted as patient-relevant in the German HTA process and led to an evidence-based additional benefit. Table 1: Patients with CKD stages 4 or 5 until Week 110"

Clinical • P3 data • Retrospective data • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Nephrology • Renal Disease

Sparsentan (SPAR) in Participants with FSGS and Collagen Type IV Alpha 3-5 Chain (COL4A3-5) Variants (KIDNEY WEEK 2025) - P3 | "Background In DUPLEX, SPAR led to sustained proteinuria reductions vs irbesartan (IRB) in participants with FSGS that were consistent in participants with podocyte gene mutations. Conclusion Consistent with the overall DUPLEX population, participants with FSGS and COL4A3-5 variants had more pronounced and durable proteinuria reductions with SPAR vs IRB. While long-term follow-up and larger sample sizes are needed to further assess SPAR’s impact in this population, findings suggest SPAR could have a meaningful impact in participants with COL4A3-5 variants, a group for which there are no approved therapies."

Focal Segmental Glomerulosclerosis • Glomerulonephritis • Renal Disease • Tumstatin

PROTECT Post Hoc Analysis: Efficacy of Sparsentan (SPAR) vs. Irbesartan (IRB) in Patients (Pts) with IgAN ≤12 mo vs. >12 mo from Kidney Biopsy (KIDNEY WEEK 2025) - "Conclusion SPAR showed better efficacy vs maximum labeled dose IRB regardless of time from biopsy, with greater kidney preservation with shorter time from biopsy. These results emphasize the value of early SPAR treatment."

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