FDA Extends Sparsentan (Filspari) sNDA Review for Focal Segmental Glomerulosclerosis
Sparsentan (Filspari), a dual endothelin-angiotensin receptor antagonist, produced greater and earlier proteinuria reduction than irbesartan in focal segmental glomerulosclerosis, though the phase 3 DUPLEX trial did not show a significant difference in eGFR slope.
What changed
Sparsentan is a first-in-class, non-immunosuppressive dual endothelin type A and angiotensin II type 1 receptor antagonist already granted accelerated FDA approval for reducing proteinuria in IgA nephropathy. Its development for FSGS centers on the phase 3 DUPLEX trial, which is the focus of ongoing regulatory review for this additional indication.
Background
FSGS is a leading cause of nephrotic syndrome and kidney failure with no FDA-approved therapies, and persistent proteinuria predicts progression. Endothelin-1 and angiotensin II signaling drive podocyte injury and glomerulosclerosis, providing the rationale for combined dual blockade with sparsentan rather than an angiotensin receptor blocker alone.
Why it matters
In DUPLEX, 371 patients with FSGS were randomized to sparsentan or irbesartan for 108 weeks. At 36 weeks, partial remission of proteinuria was achieved in 42.0% with sparsentan versus 26.0% with irbesartan, and remission was reached earlier and more often; however, there were no significant between-group differences in eGFR slope at 108 weeks. Pooled analyses confirm a greater antiproteinuric effect with sparsentan, and patients reaching remission had lower risk of kidney failure, supporting a nephroprotective benefit even though the primary eGFR endpoint was not met. Hypotension was more frequent with sparsentan, otherwise the safety profile was similar to irbesartan.
Category
Regulatory
Source
FDA
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