First-line sparsentan use associated with proteinuria reduction in IgA nephropathy
Key takeaways:
- At some point during the first 24 weeks, 58% of participants had complete remission of proteinuria.
- Mean urine protein creatinine ratio declined by 61.9% at week 4 and by 68.9% at week 24.
BOSTON — Adults recently diagnosed with immunoglobulin A nephropathy who were assigned sparsentan as first-line therapy experienced rapid and sustained reductions in proteinuria, according to researchers.
Researchers presented interim findings from the SPARTAN trial at the National Kidney Foundation Spring Clinical Meetings. SPARTAN is a phase 2, open-label, single-arm, multicenter trial of sparsentan (Filspari, Travere Therapeutics) for use as first-line therapy for adults with newly diagnosed immunoglobulin A (IgA) nephropathy. Sparsentan is an endothelin and angiotensin II receptor antagonist indicated to slow kidney function decline for adults with primary IgA nephropathy who are at risk for disease progression. The pivotal trial for FDA approval assessed use of the drug among patients with prevalent disease.
In SPARTAN, researchers administered 400 mg sparsentan for 110 weeks to 12 adults diagnosed with IgA nephropathy on biopsy within the preceding 6 months. Participants had proteinuria of at least 0.5 g/dL and eGFR at least 30 mL/min/1.73 m2. None had used an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in the 12 months before enrollment.
Mean proteinuria declined by 61.9% at week 4 and by 68.9% at week 24. At some point during treatment, 58% of participants had complete remission of proteinuria to below 0.3 g per day, according to the researchers.
“Approximately 60% of patients in the study achieved complete remission of proteinuria, a treatment target that is recommended in the draft of the 2025 [Kidney Disease: Improving Global Outcomes] guidelines for the management of IgA nephropathy,” Chee Kay Cheung, MBChB, MRCP, PhD, FHEA, a consultant nephrologist and honorary associate professor in the renal research group in the department of cardiovascular sciences in the College of Life Sciences at the University of Leicester, U.K., told Healio.
Blood pressure, total body water and body weight remained stable at week 24 from baseline.
“In addition to reducing proteinuria, treatment with sparsentan also resulted in rapid and sustained reductions in urinary soluble CD163, a biomarker for activated macrophages,” Cheung said. “This suggests that sparsentan has direct anti-inflammatory effects within the kidney. This is being investigated further, by analysis of the repeat kidney biopsies and other serum and urinary biomarkers collected in the SPARTAN study. We aim to present these findings at upcoming meetings.”
One participant left the trial due to hypotension and half of participants reported dizziness, which was the most frequent adverse event, according to the researchers.
“Data from the SPARTAN study support starting sparsentan earlier in the disease course for its renoprotective effects,” Cheung said.
For more information:
Chee Kay Cheung, MBChB, MRCP, PhD, FHEA, can be reached at ckc15@leicester.ac.uk.
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Cheung CK, et al. Abstract G-452. Presented at: NKF Spring Clinical Meetings; April 9-13, 2025; Boston.