Antiproteinuric Effect of Sparsentan in Patients with Genetic-Associated FSGS Enrolled in the DUPLEX Trial
A DUPLEX sub-analysis found that sparsentan lowered protein in the urine and led to more complete remissions than irbesartan even in patients with genetic forms of FSGS — a group that usually resists treatment.
Background
Certain genetic forms of FSGS — including variants in podocyte proteins, COL4A3-5 collagen genes, and APOL1 high-risk genotypes — are typically resistant to current treatments. DUPLEX compared sparsentan with the active control irbesartan over 108 weeks in biopsy-proven or genetic FSGS.
Study design
This post hoc exploratory analysis used next-generation sequencing to identify 31 patients with podocyte gene variants, 25 with COL4A3-5 variants, and 14 with APOL1 high-risk genotypes among DUPLEX participants, collectively termed genetic FSGS.
Key findings
Sparsentan produced substantial, sustained proteinuria reductions and numerically more frequent complete remission than irbesartan, and a lower proportion of sparsentan-treated patients reached composite kidney endpoints, consistent with the overall DUPLEX population.
Clinical implications
The findings support an antiproteinuric benefit of sparsentan in genetic FSGS, a subgroup often resistant to other interventions, though the small per-genotype numbers warrant cautious interpretation.
Category
Research
Source
Clinical Journal of the American Society of Nephrology (CJASN)
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