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Sparsentan (SPAR) is a novel, nonimmunosuppressive, single molecule dual endothelin angiotensin receptor antagonist (DEARA) approved by the US Food and Drug Administration for treatment of adults with IgA nephropathy (IgAN). SPARTAN is an open-label, single-arm, multicenter, exploratory trial, investigating the safety and efficacy of SPAR as first-line therapy in patients newly diagnosed with IgAN. We report preliminary clinical findings over the first 36 weeks of treatment.
Patients aged ≥18 years with biopsy-proven IgAN diagnosed within 6 months before enrollment, proteinuria of ≥0.5 g/day, and estimated glomerular filtration rate (eGFR) of ≥30 mL/min/1.73 m2 at screening were eligible. No previous treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers within the past 12 months was permitted. Patients receive SPAR for 110 weeks, with a 4-week safety follow-up. In addition to safety monitoring, assessments include proteinuria, glomerular filtration rate, 24-hour ambulatory blood pressure (BP), body weight, and total body water assessment (bioimpedance). Renal and cardiac magnetic resonance imaging are performed at predefined time points and repeat kidney biopsy at week 24.
At data cutoff (September 26, 2023), 12 patients had received ≥1 dose of SPAR with up to 36 weeks follow-up. Mean age at enrollment was 36 (SD 12) years (n=5 female). At baseline, median total protein excretion was 1.4 (IQR, 0.6-3.2) g/day and median urine protein-creatinine ratio (UPCR) was 1.3 (IQR, 0.4-1.7) g/g. Mean eGFR was 70 (SD 25) mL/min/1.73 m2 and mean systolic/diastolic BP was 125/78 (SD 10/10) mm Hg. At week 4, the geometric mean reduction in proteinuria (UPCR) was 62.6% from baseline, and the antiproteinuric effects were sustained over 36 weeks, with an 81.0% reduction observed at week 36 (Figure). In total, 67% of patients achieved complete remission of proteinuria (<0.3 g/day) at any time during the treatment period (Table). After an initial decrease, BP remained stable during the rest of the follow-up. eGFR changes were relatively stable over 36 weeks of treatment with SPAR. Body weight and total body water over the first 36 weeks are summarized in the Table. One patient discontinued due to hypotension.
As first-line treatment in patients newly diagnosed with IgAN, preliminary findings show SPAR was safe and generally well tolerated and reduced proteinuria >80% over 36 weeks, with minimal changes in total body water over time.