Sparsentan superior to irbesartan in focal segmental glomerulosclerosis patients, reveals DUPLEX trial

The phase III DUPLEX trial showed that sparsentan (Filspari) led to more complete and partial remissions of focal segmental glomerulosclerosis than irbesartan (Avapro).

"For a 108-week double-blind treatment period, 18.5% of sparsentan-treated patients achieved complete remission of FSGS versus 7.5% of irbesartan-treated patients (relative risk [RR] 2.47)," Michelle N. Rheault, MD, of the University of Minnesota Medical School in Minneapolis, and colleagues reported at the National Kidney Foundation (NKF) Spring Clinical meeting.

Of the patients on sparsentan, 37.5% had partial remission compared with 22.6% of those on irbesartan (RR 1.60). At the 36-week interim analysis point, those taking sparsentan also had a significantly higher probability of achieving partial remission.

FSGS is a chronic kidney disease characterized by scarring in the kidney's filtering units, leading to impaired kidney function and protein leakage into the urine. Currently, treatment options for FSGS are limited, emphasizing the urgency for novel therapeutic approaches.

The phase 3 DUPLEX trial evaluated the nephroprotective and antiproteinuric potential of the dual endothelin angiotensin receptor antagonist (DEARA) SPAR versus active control IRB in patients with FSGS. DUPLEX met its interim efficacy endpoint (EP); more patients achieved partial remission of proteinuria at 36 weeks with SPAR vs IRB. Still, after 108 wk, the greater antiproteinuric effect did not translate to a significant difference in eGFR slopes. Dr. Rheault and colleagues present additional results from the 2-y analysis.

The study included 371 patients (8-75 y) with primary or genetic FSGS, eGFR ≥30 mL/min/1.73 m2, and urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g. They were randomized in a 1:1 ratio to SPAR or IRB (800 and 300 mg/d) for 108 wk.

EPs included complete remission of proteinuria (CR; UPCR <0.3 g/g), the proportion of patients reaching composite kidney EPs, and absolute change in eGFR from baseline to 4 weeks post cessation of study drug (wk 112). Safety (adverse events) was also evaluated.

The following were the key findings of the study:

· Over 108 wk, CR was achieved earlier and more frequently with SPAR vs IRB.

· Fewer patients reached the composite kidney EPs, and the absolute decline in eGFR from baseline was numerically lower with SPAR vs IRB.

· SPAR was generally well tolerated, with no clinically meaningful fluid retention.

· There were no instances of heart failure in either group.

The study showed that SPAR led to more frequent CR and demonstrated a consistent trend of lower absolute decline in eGFR and fewer patients reaching composite kidney EPs versus IRB after two years. The findings support a potential clinical benefit of SPAR for FSGS.

Reference:

Rheault M, et al "Sparsentan vs irbesartan in patients with focal segmental glomerulosclerosis (FSGS): results from the phase 3 DUPLEX trial" NKF 2024; Poster 406.