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

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

Concomitant Sparsentan and Sodium-Glucose Cotransporter-2 Inhibitors in Adults With IgA Nephropathy in the Phase 2 SPARTACUS Trial (ERA 2025) - No abstract available

Clinical • P2 data • Glomerulonephritis • IgA Nephropathy • 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) - No abstract available

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

Sparsentan reversibly decreases mesangial IgA deposition in gddY mice; a possible role for mesangial-cell -surface autoantigen expression. (ERA 2025) - No abstract available

Preclinical • IgA Nephropathy

Effects of Sparsentan After Maximized Angiotensin Receptor Blocker (ARB) Treatment in Patients With IgA Nephropathy (IgAN) in the PROTECT Trial (ERA 2025) - No abstract available

Clinical • Glomerulonephritis • IgA Nephropathy • Renal Disease

Sparsentan reduces glomerular dysfunction and proteinuria in a rat model of serum-factor-induced nephrotic syndrome (ERA 2025) - No abstract available

Preclinical • Glomerulonephritis • Nephrology • Renal Disease

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

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

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

Travere Therapeutics Submits sNDA to FDA for Approval of FILSPARI (sparsentan) for the Treatment of FSGS (GlobeNewswire) - "Travere Therapeutics, Inc...announced the Company has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) seeking priority review for traditional approval of FILSPARI (sparsentan) for the treatment of focal segmental glomerulosclerosis (FSGS). The 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.... The Company expects to receive notice regarding the acceptance for review of the sNDA submission as well as the timeline for sNDA review from the FDA in the second quarter of 2025."

FDA filing • Focal Segmental Glomerulosclerosis

Framework for precision medicine in focal segmental glomerulosclerosis: Translation of sparsentan-responsive genes in a rat model to kidney disease associated proteins in biofluids. (PubMed, medRxiv) - "Sparsentan reversed the molecular fingerprint in kidneys of an adriamycin-challenged rat model of chronic kidney disease, consistent with the phenotypic data. Several urine proteins were associated with the sparsentan response score highlighting opportunities for the development of non-invasive surrogates of sparsentan response to enable a precision medicine approach for treatment with dual endothelin angiotensin receptor antagonists. Cross-species mapping of sparsentan response in rat and human studies identified similar networks which were elevated in a subset of people with more severe focal segmental glomerulosclerosis (FSGS) providing the basis for implementing precision medicine in for sparsentan treatment."

Journal • Preclinical • Chronic Kidney Disease • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Nephrology • Renal Disease

The Rapidly Changing Treatment Landscape of IgA Nephropathy. (PubMed, Semin Nephrol) - "This has directly resulted in the approval of three novel therapies specifically for the treatment of IgAN (nefecon, sparsentan, and iptacopan), and several others are in the late stages of clinical development. In this review, we outline the rationale for new therapies in development for IgAN and emerging clinical trial data and propose a new paradigm for the treatment of this condition."

Journal • Review • Glomerulonephritis • IgA Nephropathy • Renal Disease

Travere Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "Net product sales of FILSPARI totaled $50 million in 4Q 2024; $132 million for full year 2024....The FDA assigned a PDUFA target action date of August 28, 2025, to the Company’s supplemental New Drug Application (sNDA) requesting modification of liver monitoring for FILSPARI in IgAN....The Company’s partner, Renalys Pharma, Inc., recently completed enrollment in its registrational Phase 3 clinical trial of sparsentan for the treatment of IgAN in Japan and expects topline results in the second half of 2025....Pegtibatinase (TVT-058) – Classical HCU: The Company is continuing to make progress on the necessary process improvements in manufacturing scale-up and is on track to restart enrollment in the Phase 3 HARMONY Study in 2026."

Enrollment status • P3 data: top line • PDUFA • Sales • IgA Nephropathy • Metabolic Disorders • Rare Diseases

Real-world assessment of sparsentan's drug safety framework. (PubMed, Ren Fail) - "Based on the available AE reporting data, sparsentan exhibits a favorable safety profile, with no high-priority clinical events identified. Our findings offer valuable insights to optimize the use of sparsentan and understand its potential side effects."

Journal • Real-world evidence • Fatigue • Glomerulonephritis • Hypotension • IgA Nephropathy • Pain • Renal Disease

The road ahead: emerging therapies for primary IgA nephropathy. (PubMed, Front Nephrol) - "Sparsentan is indicated for persisting proteinuria...To reduce Gd-IgA1 production, targeted-release budesonide is approved...The terminal pathway inhibitors cemdisiran and ravulizumab show promise in phase 2 studies. Our current approach for those requiring immunosuppression involves combining the reduction of Gd-IgA1 (nefecon) with suppressing the effects of inflammation (iptacopan). The optimal duration of such therapy is uncertain. Clearly, there is more to be learned with many trials underway."

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

The dual endothelin A and angiotensin II type 1 receptor antagonist sparsentan (FILSPARI®) exhibits a safe nonclinical male fertility toxicity profile. (PubMed, Regul Toxicol Pharmacol) - "A thorough review of the results from these studies has shown no evidence of effects of sparsentan on spermatogenesis or testicular histopathology. The overall conclusion of this assessment is that sparsentan is not toxic to the testes or the spermatogenic process and is more like ARBs than ERAs in its male fertility toxicity profile."

Journal

Travere Therapeutics to Submit sNDA for FILSPARI (sparsentan) in FSGS (GlobeNewswire) - "Travere Therapeutics, Inc...announced the Company has completed its Type C meeting with the U.S. Food and Drug Administration (FDA) and plans to submit a supplemental New Drug Application (sNDA) seeking traditional approval of FILSPARI for focal segmental glomerulosclerosis (FSGS). The sNDA will be based on existing data from the Phase 3 DUPLEX and Phase 2 DUET studies of FILSPARI and is expected to be submitted around the end of the first quarter of 2025."

FDA event • FDA filing • Focal Segmental Glomerulosclerosis

Advances in Focal Segmental Glomerulosclerosis Treatment From the Perspective of the Newest Mechanisms of Podocyte Injury. (PubMed, Drug Des Devel Ther) - "Corresponding targeted medications such as Abatacept, chemokine receptor (CCR) inhibitors, CDDO-Im (2-Cyano-3,12-dioxooleana-1,9-dien-28-imidazolide), adenosine monophosphate-activated protein kinase (AMPK) activators, and Adalimumab are currently under investigation. Notably, some medications such as Rituximab and Sparsentan, may simultaneously target multiple downstream mechanisms, Furthermore, exploring molecular strategies for established medications and developing novel treatments guided by biomarkers such as Anti-CD40 antibody, blood microRNA, urinary microRNA, and tumor necrosis factor-alpha (TNF-α) may provide additional therapeutic avenues for patients with FSGS."

IO biomarker • Journal • Review • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Metabolic Disorders • Oncology • TNFA

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

Treatment of Patients with IgA Nephropathy: A call for a new paradigm. (PubMed, Kidney Int) - "A multitude of new therapies are now being evaluated in IgAN, and several drugs, such as sodium-glucose transporter-2 inhibitors, sparsentan (a dual endothelin-1 and angiotensin II receptor blocker), nefecon (a targeted release formulation of budesonide) and iptacopan (a complement factor B inhibitor) have been approved, with more to come in the next few years. In this review, we propose a new treatment paradigm that combines therapies with different mechanisms of action to target the immune components and the chronic kidney disease components of IgAN in parallel to preserve long-term kidney survival."

Journal • Review • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Renal Disease • CFB • EDN1