Engaging Patients for Better Outcomes: Informed Care for IgA Nephropathy
Explore insights from the Phase 2 SPARTACUS trial, PROTECT OLE, and real-world data evaluating use of sparsentan with SGLT2i in IgAN
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In this issue we:
- Discuss the evolving IgA nephropathy treatment paradigm
- Highlight clinical data that support sparsentan as a foundational therapy in IgA nephropathy
- Share Phase 2 SPARTACUS, Phase 3 PROTECT Open Label Extension (OLE), and real-world data evaluating the concomitant use of sparsentan and sodium-glucose cotransporter-2 inhibitors (SGLT2i)
The IgA nephropathy treatment paradigm is evolving with HCPs exploring earlier, dual-targeted treatment options in IgA nephropathy1-5
Data from the RaDaR study have encouraged the nephrology community to strive towards earlier diagnoses, and further reduction of proteinuria and preservation of kidney function.6 These goals continue to shape treatment decisions and have contributed to a growing focus on dual-targeted strategies, underscoring the importance of foundational therapy early in the disease course.1-5,7
Additionally, managing episodic immunosuppression also remains a consideration for patients who are at high-risk for disease progression.7
Rethinking IgAN: A Different Perspective from Community Nephrologists
Join two community nephrologists as they discuss how evolving data and treatment goals are reshaping IgA nephropathy management in everyday practice
Emerging treatment targets (0.3-0.5 g/g UPCR and eGFR slope <1 mL/min/1.73m2/year) are supported by clinical trial and real world data.1-5,7 The combination of well-tolerated therapies to potentially reduce proteinuria and preserve kidney function can include, but are not limited to1-5,7:
- A potential DEARA-based combination: Sparsentan combined with an SGLT2i
- A stepwise approach using separate agents: Renal angiotensin system inhibitors (RASi) with or without endothelin type A receptor (ETAR) antagonists and/or SGLT2i
Episodic immune suppression (IST) may also be used in tandem with these treatment combinations when necessary.7
Figure. IgA nephropathy evolving treatment paradigm1,7
Clinical data support the role of sparsentan as a therapeutic option in IgA nephropathy8,9
Two-year data and post hoc analyses from the Phase 3 PROTECT trial have indicated that sparsentan was associated with a greater reduction in proteinuria and preservation of kidney function compared to maximum labeled dose irbesartan.1,8 Sparsentan was also well tolerated with a safety profile comparable to irbesartan.8,9 These data suggest the potential for sparsentan as a long-term therapeutic option for IgA nephropathy.1,8
A New Dawn for IgA Nephropathy – Redefining What is Possible with Sparsentan
Watch the Travere ISN webinar to gain clinical insights into the evolving IgA nephropathy treatment landscape and the role of sparsentan
New Phase 2 SPARTACUS data presented at ERA 2025 reported data on the concomitant use of sparsentan with a SGLT2i4
SPARTACUS was an exploratory, open-label, single arm, multicenter study that assessed the safety and efficacy of replacing RASi with sparsentan in adults with IgA nephropathy (N=48) receiving stable SGLT2i therapy.4
Replacing RASi with sparsentan in patients receiving stable SGLT2i treatment resulted in rapid and sustained reductions in proteinuria, with urine protein-creatinine ratio (UPCR) percentage decreasing by approximately 45% from baseline over 24 weeks.4
Figure. SPARTACUS: Change in UPCR at each visit4
Additionally, nearly one third of patients achieved urine albumincreatinine ratio (UACR) <0.2 g/g.4
Figure. SPARTACUS: Percent of patients achieving UACR reduction endpoints at Week 244
Notably, estimated glomerular filtration rate (eGFR) remained relatively stable and blood pressure initially slightly decreased throughout the 24-week study period.4
Concomitant use of sparsentan with an SGLT2i was generally well tolerated, with no unexpected safety signals reported.4
- Most common adverse events included: hypotension (n=7), headache (n=4), edema (n=4), peripheral edema (n=4), upper respiratory tract infection (n=4), and dizziness (n=3)4
Sparsentan (SPAR) Added to Stable Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2is) in Adults With IgA Nephropathy (IgAN) in the Phase 2 SPARTACUS Trial
Explore SPARTACUS data on the combined use of sparsentan and SGLT2i in IgA nephropathy.
Previous data presented at ASN 2024 from the ongoing PROTECT OLE study report on the safety and efficacy of stable sparsentan with the addition of an SGLT2i2
PROTECT OLE findings also suggested further reduction in proteinuria and relatively stable eGFR levels.2 The combination was found to be generally well tolerated with no new safety signals identified.2
Figure. PROTECT OLE: UPCR over time with SGLT2i added to stable sparsentan treatment2
Together, data from SPARTACUS and PROTECT OLE clinical trials suggest reductions in proteinuria occurs when replacing RASi with sparsentan, and when sparsentan is used in combination with SGLT2i.2,4
Findings from real-world studies also report on the potential for combined use of sparsentan and SGLT2i3,5
Data from a real-world case series and cohort study suggested additive proteinuric benefit of concomitant use of sparsentan with SGLT2i in patients with IgA nephropathy, and the combination was generally well tolerated.3,5
In a real-world case series presented at ASN 2024, four patients with IgA nephropathy, who had been treated with steroid/immunosuppressive treatment (alone [n=2] or in combination with a RASi [n=1]), or RASi alone (n=1), were transitioned to concurrent treatment with sparsentan and SGLT2i, and were followed for a period ranging from 3-10 months.5
During the study period, concurrent use of sparsentan and SGLT2i led to reductions in proteinuria, with observed decreases in UPCR ranging from -38% after 3 months of concurrent use to -82% after 10 months.5 Two patients also achieved UPCR <0.5 g/g at any time during sparsentan treatment.5
Figure. Real-world data: Change in UPCR over 10 Months5
Notably, patients experienced further reductions in proteinuria (n=3) and albuminuria (n=1) compared with their prior treatments.5 These improvements were observed regardless of patients’ baseline proteinuria levels or eGFR.5 Renal function and blood pressure also remained relatively stable throughout the 3-10 month follow-up period.5 No treatment discontinuations occurred due to safety concerns.5
Additional real-world data published from a study across several German clinics evaluated the dual therapy approach of sparsentan in patients already receiving stable SGLT2i therapy (N=23).3
After initiation of sparsentan, UPCR decreased to a median of 0.85 (0.42-1.15) g/g at the 2-week follow-up, corresponding to a relative reduction in proteinuria of 44% from baseline.3
UPCR continued to decline further with median UPCR reaching 0.60 (0.32-0.82) g/g after 14 weeks, resulting in a relative reduction of up to 62%.3
Similar reductions were observed with UACR.3
In the authors’ analysis, these reductions in proteinuria and albuminuria were noted to be comparable to the effects observed in the PROTECT trial.3
Similar to previous findings, the combination of sparsentan and SGLT2i was well tolerated, with no drug-related serious adverse events reported.3
As healthcare professionals navigate an evolving treatment landscape, clinical trial and real-world data offer important considerations for IgA nephropathy management.2-5
ERA 2025 Expert Interview Highlights
Prof Joerg Latus (Robert Bosch Hospital, DE) and Dr Chee Kay Cheung (University Hospitals of Leicester NHS Trust, UK) reflect on key ERA 2025 data and provide their expert perspectives on the evolving RKD landscape.
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ASN 2024 Spotlight: New Treatment Targets in IgA Nephropathy
Explore insights from the Phase 2 SPARTACUS trial, PROTECT OLE, and real-world data evaluating use of sparsentan with SGLT2i in IgAN
Learn moreReferences
- KDIGO Clinical Practice Guidelines for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV). Accessed 22 October 2024. https://kdigo.org/wp-content/uploads/2024/08/KDIGO-2024-IgAN-IgAV-Guideline-Public-Review-Draft.pdf.
- Kooienga I et al. Poster presented at: American Society of Nephrology Kidney Week 2024; October 23-27, 2024; San Diego, CA. FR PO851.
- Schanz M et al. Clin Kidney J. 2025;18(1):sfae394.
- Ayoub I et al. Presented at: European Renal Association 2025; June 4 7, 2025; Vienna, Austria.
- Ravipati P et al. Poster presented at: American Society of Nephrology Kidney Week 2024; October 23-27, 2024; San Diego, CA. FR PO906.
- Pitcher D et al. Clin J Am Soc Nephrol. 2023;18(6):727 738.
- Barratt J et al. Front Med (Lausanne). 2024;11:1461879.
- Rovin BH et al. Lancet. 2023;402(10417):2077 2090.
- FILSPARI® (sparsentan) Prescribing Information. San Diego, CA: Travere Therapeutics, Inc. 9/2024.
MA-SP-25-0108 | August 2025