Patients in DUPLEX Achieved Partial or Complete Remission of Proteinuria Earlier and More Often With Sparsentan vs Irbesartan: Implications for Slowing Progression to Kidney Failure in Focal Segmental Glomerulosclerosis (FSGS)
Topics: Nephrology FSGS Phase 3 Sparsentan DUPLEX
Tumlin J, Tesar V, Trimarchi H et al.
About the research
Summary
Background
- Focal segmental glomerulosclerosis (FSGS) is a rare, progressive kidney condition defined by a histological pattern of glomerular and podocyte injury1-3
- It is associated with a high symptom, patient, and financial burden, including a substantial risk of kidney failure1,4-8
- There are no FDA-approved therapies for FSGS, highlighting an unmet need for safe and effective treatments1,9
- PARASOL identified proteinuria as a biologically plausible and clinically meaningful endpoint, with lower proteinuria strongly associated with reduced kidney failure risk1,10
- Sparsentan is a novel, non-immunosuppressive Dual Endothelin Angiotensin Receptor Antagonist (DEARA) that led to rapid and sustained proteinuria reductions in patients with FSGS in the phase 3 DUPLEX trial and phase 2 DUET study compared to maximum labeled dose irbesartan1,11-15
- Sparsentan was well-tolerated and has a similar safety profile to irbesartan12,15
Aim
To investigate the impact of sparsentan 800 mg/day vs irbesartan 300 mg/day on partial remission (urine protein-creatinine ratio [UPCR] ≤1.5 g/g and >40% reduction from baseline) or complete remission (CR) (<0.3 g/g) of proteinuria and the effect of achieving these targets on progression to kidney failure in DUPLEX1
Figure. DUPLEX study design
About the figure
Analyses by treatment arm evaluated the proportion of patients achieving partial remission or CR of proteinuria at any time through 108 weeks
Pooled analyses using data from both treatment arms evaluated rates of progression to kidney failure in patients who achieved vs those who did not achieve low proteinuria
Key findings
Patients achieved partial remission of proteinuria earlier and more often with sparsentan vs maximum labeled dose irbesartan1
Findings demonstrated a 1.5-fold higher rate of partial remission with sparsentan vs maximum labeled dose irbesartan over 108 weeks1
Figure. Probability of achieving partial remission† of proteinuria through 108 weeks1
About the figure
The rate of partial remission† of proteinuria at 108 weeks was 64.7% (119/184) with sparsentan vs. 43.9% (82/187) with irbesartan (Relative risk: 1.48, 95% CI: 1.23 to 1.78)1
*P value generated from a stratified Cox proportional hazards model with treatment and baseline log (UPCR) as covariates, stratified by randomization stratification factors1
†UPCR ≤1.5 g/g and >40% reduction from baseline (also FSGS partial remission endpoint [FPRE])1
Patients achieved CR of proteinuria earlier and more often with sparsentan vs maximum labeled dose irbesartan1
Findings demonstrated a 2.5-fold higher rate of complete remission with sparsentan vs maximum labeled dose irbesartan over 108 weeks1
Figure. Probability of achieving complete remission† of proteinuria through 108 weeks1
About the figure
The rate of CR of proteinuria at 108 weeks was 18.5% (34/184) with sparsentan vs 7.5% (14/187) with irbesartan (Relative risk: 2.47, 95% CI: 1.37 to 4.45)1
*P value generated from a stratified Cox proportional hazards model with treatment and baseline log (UPCR) as covariates, stratified by randomization stratification factors1
†UPCR <0.3 g/g1
Patients who achieved low proteinuria were less likely to reach kidney failure vs those who did not, irrespective of treatment arm1
Figure. Probability of reaching kidney failure through 108 weeks†1
About the figure
Kidney failure occurred in 3.0% (6/201) of patients who achieved partial remission‡ of proteinuria vs 15.9% (27/170) of those who did not (Relative risk: 0.33, 95% CI: 0.11 to 0.95)1
Kidney failure occurred in 2.1% (1/48) of patients who achieved CR§ of proteinuria vs 9.9% (32/323) of those who did not (Relative risk: 0.23, 95% CI: 0.03 to 1.85)1
*Confirmed estimated glomerular filtration rate (eGFR) of <15 mL/min/1.73 m2 or kidney replacement therapy1
†Results from post hoc analyses using pooled data irrespective of treatment arm1
‡UPCR ≤1.5 g/g and >40% reduction from baseline (also FPRE)1
§UPCR <0.3 g/g1
Sparsentan 800 mg/day was well tolerated with a safety profile comparable to that of irbesartan1
The most common treatment emergent adverse events (TEAEs) (≥15% of patients in any group) included1:
- COVID-19
- Hyperkalemia
- Peripheral edema
- Hypotension
Table. Adverse events1
About the figure
TEAEs were experienced by 93% (172/184) of patients with sparsentan and 93% (174/187) of patients with irbesartan1
Serious TEAEs were experienced by 37% (68/184) of patients with sparsentan and 44% (82/187) of patients with irbesartan1
Conclusions
In the DUPLEX study, patients with FSGS experienced rapid and sustained reduction in proteinuria with sparsentan compared to maximum labeled dose irbesartan1
Partial and complete remission was achieved earlier and more often with sparsentan1
Those who experienced low proteinuria had a lower risk of kidney failure1
Sparsentan 800 mg/day was generally well tolerated over 108 weeks of treatment1
Related Content
Footnotes
Sparsentan is not FDA approved for the treatment of FSGS.
CI, confidence interval; COVID-19, coronavirus disease of 2019; DEARA, Dual Endothelin Angiotensin Receptor Antagonist; eGFR, estimated glomerular filtration rate; FPRE, FSGS partial remission endpoint; FSGS, focal segmental glomerulosclerosis; TEAE, treatment-emergent adverse event; UPCR, urine protein-creatinine ratio.
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MA-SP-25-0054 | May 2025