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

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

Clinical Practice Gaps in the Diagnosis and Management of Immunoglobulin A Nephropathy (ERA 2025) - " •395 nephrologists completed all questions within the data collection timeframe •76% of nephrologists saw between 1 and 10 patients per month with IgAN •38% failed to recognise that the RaDaR study showed that IgAN is progressive even in patients thought to be at low risk (proteinuria < 1 g/d) •17% could not correctly identify that the most common clincial presentation of IgAN is asymptomatic microscopic hematuria and proteinuria •44% did not recognise the presence of tubular atrophy (T), a finding of the MEST-C score, is a consistent, independent predictor of worse outcomes in patients with IgAN •34% did not identify the correct order of the multihit hypothesis of the pathophysiology of IgAN •Only 21% knew that production of Gd-IgA1 is a mechanism via which the cytokines a proliferation inducing ligand (APRIL) and B-cell activating factor (BAFF) drive IgAN pathogenesis •66% did not recognise that, according to 2021 KDIGO guidelines, considering enrollment in a..."

Clinical • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Renal Disease

Implications of proteinuria remission on estimated glomerular filtration rate (eGFR) trajectory in patients with IgA nephropathy in the PROTECT trial (UKKW 2025) - "Background : In PROTECT, sparsentan (SPAR) reduced proteinuria and increased the proportion of patients achieving complete proteinuria remission (CR; urine protein excretion [UPE] <0.3 g/day) (31%) vs irbesartan (IRB) (11%). In IgAN, achievement of low proteinuria is strongly predictive of better long-term kidney function. eGFR preservation was more evident in patients who achieved low proteinuria vs those who did not; notably, in patients who achieved CR, the mean rate of kidney function decline (eGFR chronic slope) was <1.0 mL/min/1.73 m2/year. As SPAR-treated patients achieved proteinuria remission more frequently vs IRB in PROTECT, this analysis further supports the benefit of SPAR for long-term preservation of kidney function."

Clinical • Glomerulonephritis • IgA Nephropathy • Renal Disease

Concomitant sparsentan (SPAR) and SGLT2 inhibitors in patients with IgA nephropathy in the PROTECT open-label extension (OLE) (UKKW 2025) - "Background : SPAR, a non-immunosuppressive, dual endothelin angiotensin receptor antagonist (DEARA), demonstrated superior efficacy for proteinuria reduction and better preservation of kidney function vs irbesartan in patients with Immunoglobulin A nephropathy (IgAN) in the PROTECT trial. These data show that an SGLT2i added to a stable dose of SPAR is generally well tolerated and may lead to further reductions in proteinuria. The safety and efficacy of sparsentan with or without concomitant SGLT2i treatment are also being investigated in a separate randomised sub-study within the PROTECT OLE."

Clinical • Cardiovascular • Glomerulonephritis • Hypertension • Hypotension • IgA Nephropathy • Infectious Disease • Novel Coronavirus Disease • Renal Disease

Concomitant sparsentan (SPAR) and SGLT2 inhibitors in adults with IgA nephropathy in the ongoing phase 2 SPARTACUS trial (UKKW 2025) - "Enrolment in SPARTACUS will allow for assessment of the efficacy and safety of SPAR added to a stable SGLT2i in patients with IgAN. The poster will include data from the interim analysis."

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

Sparsentan (SPAR) as first-line treatment of incident patients with IgA nephropathy: interim analysis of the SPARTAN trial (UKKW 2025) - P2 | "In patients newly diagnosed with IgAN, interim findings show that SPAR as first-line treatment was generally well tolerated and led to rapid and sustained reductions in proteinuria by approximately 70% over 24 weeks, with reductions in urinary sCD163 indicative of a direct anti- inflammatory effect."

Clinical • Glomerulonephritis • Hypotension • IgA Nephropathy • Renal Disease • CD163

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

Interventions for idiopathic steroid-resistant nephrotic syndrome in children. (PubMed, Cochrane Database Syst Rev) - "Calcineurin inhibitors may increase the likelihood of complete or partial remission compared with placebo/no treatment or cyclophosphamide. For other regimens, it remains unclear whether the interventions alter outcomes because the certainty of the evidence is low. Further adequately powered, well-designed RCTs are needed to evaluate other regimens for children with idiopathic SRNS. Since SRNS represents a spectrum of diseases, future studies should enrol children from better-defined groups of people with SRNS."

Clinical • Journal • Review • Cardiovascular • Dermatology • Glomerulonephritis • Hypertension • Infectious Disease • Nephrology • Pediatrics • Renal Disease • Transplantation

Travere Therapeutics Announces FDA Acceptance of sNDA for FILSPARI (sparsentan) in FSGS (Businesswire) - "Travere Therapeutics...announced that the U.S. Food and Drug Administration (FDA) has accepted its supplemental New Drug Application (sNDA) for traditional approval of FILSPARI (sparsentan) for the treatment of focal segmental glomerulosclerosis (FSGS). The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of January 13, 2026, and has indicated that it is currently planning to hold an advisory committee meeting to discuss the application....The sNDA submission is supported by results from the Phase 3 DUPLEX Study and the Phase 2 DUET Study, two of the largest head-to-head interventional studies conducted to date in adult and pediatric patients with FSGS."

FDA filing • PDUFA • Focal Segmental Glomerulosclerosis

CSL Vifor and Travere Therapeutics announce standard EU approval for FILSPARI in IgA Nephropathy (PRNewswire) - "CSL Vifor and Travere Therapeutics, Inc...are pleased to announce that the European Commission has approved the conversion of the conditional marketing approval (CMA) into a standard marketing authorization (MA) for FILSPARI for the treatment of adults with primary IgA nephropathy with a urine protein excretion ≥1.0 g/day (or urine protein-to-creatinine ratio ≥0.75 g/g). Standard MA is granted for all member states of the European Union, as well as in Iceland, Liechtenstein and Norway....The approval is based on a comprehensive clinical data set, including positive confirmatory results from the pivotal phase-III PROTECT study demonstrating that FILSPARI significantly slowed kidney function decline over two years compared to irbesartan."

EMA approval • IgA Nephropathy

Comparison of Sparsentan and Irbesartan in FSGS (DocWire) - P3 | N=371 | DUPLEX (NCT03493685) | Sponsor: Travere Therapeutics, Inc. | "The DUPLEX trial (NCT03493685) determined that the dual endothelin angiotensin receptor antagonist sparsentan resulted in sustained proteinuria reduction among patients with focal segmental glomerulosclerosis (FSGS). Researchers sought further insights by comparing the effects of sparsentan and irbesartan on proteinuria remission and assessed how achieving complete or partial remission affected progression to kidney failure. Results were presented at the National Kidney Foundation Spring Clinical Meetings 2025....Patients with FSGS received sparsentan 800 mg/d (n=184) or irbesartan 300 mg/d (n=187) during the phase 3, 108-week trial. The study end points included proteinuria partial remission (urine protein-to-creatinine ratio [UPCR] ≤1.5 g/g and >40% reduction from baseline) or complete remission (UPCR <0.3 g/g)."

P2 data • Focal Segmental Glomerulosclerosis

Research trends and performance of endothelin A receptor antagonist in kidney care: a bibliometric analysis. (PubMed, Ren Fail) - "A major milestone was the accelerated FDA approval of sparsentan for IgAN in 2023, followed by full approval in 2024 based on confirmatory efficacy data...The expanding role of ERAs in nephrology underscores their potential in treating proteinuric kidney diseases. Ongoing international collaborations are advancing research on ERA safety, efficacy, and novel therapeutic strategies, supporting their broader clinical application."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Diabetic Nephropathy • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Hypertension • IgA Nephropathy • Nephrology • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases

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

EPPIK: Study of Sparsentan Treatment in Pediatrics With Proteinuric Glomerular Diseases (clinicaltrials.gov) - P2 | N=67 | Recruiting | Sponsor: Travere Therapeutics, Inc. | Trial completion date: Jun 2025 ➔ Apr 2027 | Trial primary completion date: May 2025 ➔ Mar 2027

Trial completion date • Trial primary completion date • Focal Segmental Glomerulosclerosis • Genetic Disorders • Glomerulonephritis • IgA Nephropathy • Pediatrics • Renal Disease • Vasculitis • COL4A5

Sparsentan (SPAR) as First-Line Treatment of Incident Patients With IgA Nephropathy (IgAN): Interim Analysis of the SPARTAN Trial (NKF-SCM 2025) - P2 | "Rapid and sustained reductions in urinary sCD163 were observed (Table). The most frequent AE was dizziness (50% pts); 1 pt discontinued due to hypotension.Conclusion SPAR as first-line treatment was generally well tolerated, with reductions in proteinuria ≈70% and urinary sCD163 ≈50% over 24 wks."

Clinical • Glomerulonephritis • Hypotension • IgA Nephropathy • Renal Disease

Patients (Pts) in DUPLEX Achieved Partial or Complete Remission of Proteinuria Earlier and More Often With Sparsentan (SPAR) vs Irbesartan (IRB): Implications for Slowing Progression to Kidney Failure (KF) in Focal Segmental Glomerulosclerosis (FSGS) (NKF-SCM 2025) - P3 | "SPAR was generally well tolerated, with no new safety concerns.Conclusion Pts with FSGS achieved PR and CR more rapidly and with higher incidence with SPAR vs IRB. Pts who reached PR or CR showed markedly reduced risk of progression to KF vs those who did not, supporting the nephroprotective benefit of SPAR in FSGS."

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

Choosing the Right "Target" in IgA Nephropathy: A Case Series (NKF-SCM 2025) - "It is characterized by a high first-pass metabolism, making it preferable to prednisone due to its reduced systemic side effects. New treatments, such as oral iptacopan (complement pathway inhibitor) and sparsentan (endothelin antagonist), reduce IgAN disease activity via different mechanisms than TRF-budesonide. Further data and research are needed to help clinicians choose the ideal targets for their IgAN patient."

Clinical • Acne Vulgaris • CNS Disorders • Glomerulonephritis • Hypertension • IgA Nephropathy • Insomnia • Nephrology • Renal Disease • Sleep Disorder

Improving Proteinuria With Sparsentan (SPAR) in Patients (Pts) With IgA Nephropathy (IgAN): A Case Series (NKF-SCM 2025) - "In the PROTECT trial, SPAR reduced proteinuria and led to complete proteinuria remission (CR) more often vs maximum labeled dose irbesartan; SPAR was well tolerated, with 95% of pts titrated to the target dose (400 mg/d).Methods Five pts with biopsy-proven IgAN (aged ≈35-65 y) received SPAR (treatment duration, 4-12 mo). SPAR was generally well tolerated. In 2 pts with intolerance to the 400-mg/d dose, dose reduction to 200 mg/d was well tolerated without diminished effectiveness (both pts achieved UPCR <0.5 g/g; 1 achieved <0.3 g/g).Conclusion This case series supports the benefit of SPAR on achieving low proteinuria in pts with IgAN, irrespective of UPCR and eGFR at initiation or treatment history."

Clinical • Glomerulonephritis • IgA Nephropathy • Renal Disease