Sparsentan for Focal Segmental Glomerulosclerosis in the DUET Open-Label Extension: Long-term Efficacy and Safety
Topics: Nephrology FSGS Sparsentan DUET Clinical Summary
Campbell KN, Gesualdo L, Murphy E, et al.
10.1016/j.xkme.2024.100833
Summary
DUET open-label extension (OLE) study: Long-term outcomes of sparsentan1
Background
Focal segmental glomerulosclerosis (FSGS) is a rare, progressive kidney condition marked by proteinuria and increased risk of kidney failure (KF), with few treatment options and no FDA-approved pharmacological therapies.1-4
Sparsentan is a novel, non-immunosuppressive, dual endothelin and angiotensin receptor antagonist (DEARA) that reduced proteinuria in patients with FSGS, compared with irbesartan in the initial 8-week phase of the sparsentan DUET study.1,5
Aim
This study aimed to assess the long-term efficacy and safety of sparsentan in patients with FSGS (N=108)* during the open-label extension (OLE) of the Phase 2 DUET study.1
Approach
Patients with FSGS (excluding those with known secondary causes) who received sparsentan at 200, 400, or 800 mg/d were examined from the first dose through 4.6 years.1
Key outcomes included urinary protein-creatinine ratio (UPCR), FSGS partial remission endpoint (FPRE; UPCR ≤1.5 g/g and >40% reduction from baseline), estimated glomerular filtration rate (eGFR), and blood pressure.1 Safety was assessed via treatment-emergent adverse events (TEAEs).1
Findings
The DUET OLE sparsentan study showed the following effects over the long-term follow-up period1:
- UPCR was rapidly reduced and remained low over more than four years
- More than 50% of patients had achieved FPRE after the first year
- Achieving FPRE within nine months of the first sparsentan dose was associated with slower eGFR decline vs. not achieving FPRE within nine months
- Entire treatment period: −2.70 vs. −6.56 mL/min/1.73 m²/year
- First two years of treatment: −1.69 vs. −6.46 mL/min/1.73 m²/year
Read about patients in the DUET Study who achieved complete remission (CR) [UPCR <0.3 g/g].
Long-term sparsentan treatment showed a consistent safety profile1:
- The most common TEAEs (>9 cases/100 patient-years) were:
- Headache
- Peripheral edema
- Upper respiratory infection
- Hyperkalemia
- Hypotension
- No heart failure or deaths were reported during the study
Key takeaway
In the DUET study, sparsentan use in the OLE demonstrated sustained proteinuria reductions and a consistent safety profile with no new or unexpected adverse effects in patients with FSGS.1 Early achievement of partial remission correlated with slower kidney function decline.1
Footnotes
*Treatment of forty-five patients was ongoing at data cutoff at 4.6 years.
Sparsentan is not FDA-approved for the treatment of FSGS.
DEARA, dual endothelin angiotensin receptor antagonist; eGFR, estimated glomerular filtration rate; FPRE, focal segmental glomerulosclerosis partial remission endpoint; FSGS, focal segmental glomerulosclerosis; TEAE, treatment-emergent adverse event; UPCR, urinary protein-creatinine ratio.
- Campbell KN et al. Kidney Med. 2024;6(6):100833.
- D’Agati VD et al. N Engl J Med. 2011;365(25):2398-2411.
- De Vriese AS et al. Nat Rev Nephrol. 2021;17(9):619-630.
- Spino C et al. Front Pediatr. 2016;4(25).
- Trachtman H et al. J Am Soc Nephrol 2018;29(11):2745.
MA-SP-25-0088 | July 2025