Study of the efficacy of sparsentan/sparsentan and irbesartan using genetic FSGS

The DUPLEX trial examined the efficacy and safety of two potential treatments for focal segmental glomerulosclerosis (FSGS): Sparsentan and irbesartan. Sparsentane shows a significant reduction in proteinuria, but it is unclear whether its efficacy depends on the underlying pathogenesis of FSGS.

Hereditary FSGS (gFSGS) is caused by mutations in the podocyte gene and is often difficult to treat. In a post hoc analysis of DUPLEX data, the efficacy of spaxentane in a subpopulation of patients with gFSGS was evaluated. Their results were shared in a poster at ASN Kidney Week 2024 titled Duplex Trial Results in Patients with Hereditary Focal Segmental Glomerulosclerosis (gFSGS).

The FSGS Preventive Genetics Group genotyped 355 bipolar patients. People with pathogenic or likely pathogenic variants in podocyte genes are classified as having gFSGS with Mendelian inheritance. Overall, 8.7% (n=31) of patients were identified as having gFSGS. Compared with the entire bipolar population at baseline, these patients were younger, had higher eGFR, and most had proteinuria in the nephrotic range.

Post hoc analyzes examined changes in proteinuria, i.e., the percentage of patients who reduced or achieved complete remission (urinary protein to creatinine ratio <0.3 g/g at any time) with sparsentan compared with irbesartan and the percentage of patients who achieved end-stage renal disease (eGFR <15 mL/min/1.73 m2, dialysis or transplant). Sparsentan reduces proteinuria more rapidly and significantly than irbesartan. This effect was sustained and was also observed in a subgroup of patients with NPHS2 mutations.

The only patients with gFSGS who achieved a complete response were those who received sparsentane (n=1 [8%] vs n=0). End-stage renal disease was more common in gFSGS patients taking irbesartan (n=3 [17%] vs n=1 [8%]). Marked early antiproteinuric reactions that persisted during treatment were more common with sparsentan than with irbesartan. The researchers concluded: These findings support recommendations for dosing [sparsentan] to reduce proteinuria and achieve long-term renal health benefits in this high-risk gFSGS patient population.

References:https://www.docwirenews.com/post/effect-of-sparsentan-versus-irbesartan-with-genetic-fsgs