Efficacy and Safety of Sparsentan Compared with Irbesartan in Patients with Primary Focal Segmental Glomerulosclerosis: Randomized, Controlled Trial Design (DUET)
Kidney International Reports – 2017
Sparsentan for Focal Segmental Glomerulosclerosis in the DUET Open-Label Extension: Long-term Efficacy and Safety
Journal article
Published on April 26, 2024
Contributors:
Campbell KN, Gesualdo L, Murphy E, et al.
Campbell KN, Gesualdo L, Murphy E, et al.
DOI:
10.1016/j.xkme.2024.100833
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
Related Content
Efficacy and Safety of Sparsentan Compared with Irbesartan in Patients with Primary Focal Segmental Glomerulosclerosis: Randomized, Controlled Trial Design (DUET)
Kidney International Reports – 2017
DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGS
Journal of the American Society of Nephrology – 2018
Implications of Complete Proteinuria Remission at Any Time in Focal Segmental Glomerulosclerosis: Sparsentan DUET Trial
Kidney International Reports – 2023
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