Sparsentan 400mg tablets

Sparsentan has shown positive effects on managing different subtypes of glomerulonephritis. The recent results of trials require a pooled analysis to validate these results. We aim to assess the safety and efficacy of sparsentan versus irbesartan for patients with IgA nephropathy and focal glomerulosclerosis (FSGS). We conducted a systematic review and meta-analysis of randomized controlled trials retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through March 2024. We used Review Manager v.5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). Three studies with a total of 884 patients were included. Sparsentan was superior to irbesartan in improving urine protein to creatinine ratio (UP/C) (ratio of percentage reduction 0.66, 95% CI [0.58 to 0.74], P < 0.001); as well as the proportion of patients achieved complete and partial remission of proteinuria (RR = 2.57, 95% CI [1.73 to 3.81], P < 0.001) and (RR = 1.63, 95% CI [1.4 to 1.91], P < 0.001) respectively. Regarding the effect on the glomerular filtration rate, the results estimate did not favor either sparsentan or irbesartan (MD = 1.98 ml/min per 1.73mm2, 95% CI [-1.05 to 5.01], P = 0.2). There were no significant differences in adverse events except for hypotension, which showed higher rates in the sparsentan group (RR = 2.02, 95% CI [1.3 to 3.16], P = 0.002). Sparsentan is effective and has a good safety profile for treating FSGS and patients with IgA nephropathy. However, more well-designed RCTs against ARBs, ACE inhibitors, and steroids with larger sample sizes are needed to get conclusive evidence.

Abstract licence: CC BY-NC-ND 4.0

Aim: We compared the effects of nefecon, an oral targeted-release budesonide formulation, and sparsentan, an oral, dual endothelin-angiotensin receptor antagonist, on estimated glomerular filtration rate (eGFR) in patients with immunoglobulin A nephropathy, a leading cause of chronic kidney disease. Materials & methods: We conducted an anchored matching-adjusted indirect comparison (MAIC) using patient-level data from NefIgArd (NCT03643965; n = 364), a randomized (1:1) trial of nefecon plus optimized renin–angiotensin system inhibitor (RASi) therapy versus placebo plus RASi; and aggregate data from PROTECT (NCT03762850; n = 404), a randomized (1:1) trial of sparsentan versus irbesartan, an angiotensin receptor blocker. Mean absolute eGFR change and mean relative urine protein-to-creatinine and urine albumin-to-creatinine ratio changes from baseline at 9, 12 and 24 months (NefIgArd) or 36, 48 and 106 weeks (PROTECT) were analyzed using amixed-effects model for repeated measures. A composite outcome (time to confirmed 40% eGFR reduction, end-stage kidney disease or all-cause mortality) was also included. An unanchored MAIC and network meta-analysis were used as sensitivity analyses. Results: The matching process reduced the effective sample for the NefIgArd trial from 364 to 208. Absolute eGFR change significantly favored nefecon over sparsentan at 9 months (mean difference,ml/min/1.73m2 [95% credible interval]: 5.7 [3.1–8.2]), 12 months (3.5 [1.0–6.0]) and 24 months (3.3 [0.0–6.5]). Differences in other outcomes were generally not statistically significant. Sensitivity analysis results were consistent with the main findings. Conclusion: In patients with immunoglobulin A nephropathy, nefecon plus optimized RASi may preserve kidney function to a greater extent than sparsentan.

Abstract licence: CC BY