Effects of sparsentan and irbesartan on FSGS gene

In a clinical trial called DUPLEX (NCT03493685), researchers evaluated the effect of the dual endothelin-angiotensin receptor antagonist sparsentane on proteinuria in patients with focal segmental glomerulosclerosis (FSGS). The aim of the trial is to compare the effectiveness of Sparsentan with the traditional drug irbesartan in relieving proteinuria and to explore whether these remissions influence the progression of kidney failure.

The DUPLEX trial was a 108-week Phase 3 clinical trial involving 371 FSGS patients. Of these, 184 patients received sparsentan 800 mg daily, and 187 patients received irbesartan 300 mg daily. The primary endpoint of the study included partial and complete remission of proteinuria, defined as urine protein to creatinine ratio (UPCR) ≤1.5 g/g and a reduction of more than 40% from baseline (partial remission), or UPCR <0.3 g/g (complete remission). Additionally, researchers investigated the impact of remission on progression of renal failure, as assessed by estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m² or the need for renal replacement therapy.

The study found that patients treated with sparsentan achieved partial and complete remission of proteinuria earlier and more frequently than those treated with irbesartan. This shows that sparsentin has obvious advantages in the treatment of FSGS. Furthermore, resolution of proteinuria significantly reduced the risk of progression of renal failure regardless of treatment, further supporting the use of spaxantane in this area. Safety analysis showed that sparsentin was well tolerated and no new safety issues emerged. Taking both efficacy and safety into consideration, the study results support the use of spaxantane in the treatment of FSGS.

Further analysis focused on responses in patients with hereditaryFSGS (gFSGS). gFSGS is usually caused by podocyte gene mutations and is difficult to treat. In a post hoc analysis of the DUPLEX data, the efficacy of spaxantane in this subpopulation was assessed. The study results, presented at a poster session at ASN Kidney Week 2024, explore how patients with gFSGS fared in the dual trial.

atFSGS遗传学小组中，有355名患者接受了基因分型，结果显示8.7%的患者（n=31）被确定为患有gFSGS。 These patients are younger relative to the entire bipolar population, have higher glomerular filtration rates (eGFR), and most have nephrotic range proteinuria.这一发现提示，gFSGS患者在基线状态下的肾功能可能较好，但仍需关注其疾病的进展。

In post hoc analyses, the researchers focused on changes in proteinuria, including the proportion of patients who experienced a reduction or complete remission with sparsentan compared with irbesartan, and the proportion of patients who ultimately developed end-stage renal disease (eGFR <15 mL/min/1.73 m², dialysis or transplantation). The results showed that sparsentan was significantly more effective than irbesartan in reducing proteinuria, and this effect was also verified in a subgroup of patients harboring NPHS2 mutations.

The only patient with gFSGS who achieved complete remission was a patient treated with sparsentan (n=1,8%), and the incidence of end-stage renal disease was higher among gFSGS patients taking irbesartan (n=3,17% vs. n=1,8%).持续的显著早期抗蛋白尿反应在斯帕森坦治疗组中更为常见。

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