Latest news on sparsentan/sparsentan 2025

Glomerulonephritis is a heterogeneous immune-mediated disease that mainly causes glomerular damage. It is one of the most common causes of impaired renal function and accounts for approximately 10-15% of end-stage renal disease cases. Among the various types of glomerulonephritis, immunoglobulin A nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) are associated with high morbidity and mortality in both adults and children. The clinical manifestations of IgAN are diverse, ranging from asymptomatic hematuria to rapidly progressive glomerulonephritis.

In recent years, endothelin receptor antagonists (ERA) such as atrasentan, avosentan, spaxentan, and TAK-044 have been proposed to prevent disease progression, although their success in clinical applications has been limited. These drugs show some effectiveness in reducing proteinuria or albuminuria, but the improvement in glomerular filtration rate (GFR) is not significant. Sparsentan/Sparsentan (Sparsentan), as a new oral dual ERA and angiotensin II receptor antagonist, was approved by the FDA in February 2023 for the treatment of patients with IgAN. Its mechanism mainly relies on the selective antagonism of endothelin type A receptors and angiotensin II receptors, which are closely related to the pathogenesis of IgA nephropathy and FSGS.

There is a lack of systematic evaluation of studies on the efficacy of sparsentane, so this study aimed to verify the results of randomized controlled trials (RCTs) through meta-analysis to establish more conclusive evidence. Our objective was to evaluate the safety and efficacy of sparsentan versus irbesartan in the treatment of patients with IgA nephropathy and FSGS. Research methods include a systematic review and meta-analysis of multiple randomized controlled trials up to 2024, and comprehensive evaluation of each result through risk ratio (RR) and mean difference (MD).

The research results showed that a total of 884 patients participated in three related studies. In terms of improving the urine protein to creatinine ratio (UP/C), sparsentan was significantly better than irbesartan, with a percentage reduction rate of 0.66 (95% confidence interval [CI]: 0.58-0.74, P<0.001). In addition, in terms of the proportion of patients achieving complete remission and partial remission of proteinuria, the performance of the sparsentan group was also better than that of irbesartan, with RRs of 2.57 (95% CI: 1.73-3.81, P<0.001) and 1.63 (95% CI: 1.4-1.91, P<0.001) respectively. However, regarding the impact of GFR, the results did not show a significant difference between sparsentan and irbesartan (MD=1.98ml/min/1.73 m², 95%CI: -1.05-5.01, P=0.2). Except for hypotension, there was no significant difference in the incidence of other adverse events, but the incidence of hypotension was higher in the sparsentan group (RR=2.02, 95%CI: 1.3-3.16, P=0.002).

To sum up, sparsentin in treatmentIt has demonstrated good efficacy and safety in patients with FSGS and IgA nephropathy. However, in order to further verify these results, more well-designed randomized controlled trials are still needed, especially comparative studies of ARBs, ACE inhibitors and steroids, to obtain conclusive evidence with a larger sample size.

Reference materials:https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03713-9