The following is a summary of “Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis,” published in the November 2023 issue of Nephrology by Rheault et al.
Despite ineffective treatments for focal segmental glomerulosclerosis (FSGS), the drug sparsentan reduced proteinuria in patients with FSGS in an 8-week, phase 2 trial. Researchers performed a retrospective study to assess the efficacy and safety of long-term treatment with sparsentan for FSGS.
Patients aged 8 to 75 years with FSGS (without known secondary causes) were enrolled and randomly assigned to receive either sparsentan or irbesartan (active control) for 108 weeks. The interim analysis at 36 weeks assessed a surrogate efficacy endpoint that was FSGS partial remission of proteinuria (defined as a urinary protein-to-creatinine ratio of ≤1.5 [with protein and creatinine both measured in grams] and a >40% reduction in the ratio from baseline). The primary efficacy endpoint was the estimated glomerular filtration rate (eGFR) slope at the final analysis. The secondary endpoint was the change in eGFR from baseline to 4 weeks after treatment (week 112), and safety was also evaluated.
About 371 patients were randomized, with 184 receiving sparsentan and 187 receiving irbesartan. At 36 weeks, 42.0% of patients in the sparsentan group achieved partial remission of proteinuria, compared to 26.0% in the irbesartan group (P=0.009). This response was sustained through 108 weeks. At the final analysis at week 108, there were no significant differences in the eGFR slope between the two groups. The total slope (day 1 to week 108) showed a between-group difference of 0.3 ml per minute per 1.73 m2 of body-surface area per year (95% CI, -1.7 to 2.4), and the chronic slope from week 6 to week 108 had a between-group difference of 0.9 ml per minute per 1.73 m2 per year (95% CI, -1.3 to 3.0). The mean change in eGFR from baseline to week 112 was -10.4 ml per minute per 1.73 m2 with sparsentan and -12.1 ml per minute per 1.73 m2 with irbesartan, (difference, 1.8 ml per minute per 1.73 mm2; 95% CI, −1.4 to 4.9). The safety profiles of sparsentan and irbesartan were similar, and the frequency of adverse events was comparable between the two groups.
The study found sparsentan reduced proteinuria more than irbesartan in patients with FSGS but did not improve the rate of decline in kidney function.
Source: nejm.org/doi/full/10.1056/NEJMoa2308550
