On August 16, 2021, travere therapeutics announced that sparsentan, a drug under research for the treatment of IgA nephropathy (IgAN), obtained positive preliminary interim results in the ongoing key phase 3 clinical trial protect. After 36 weeks of treatment, the decrease of proteinuria in sparsentan group compared with baseline was more than three times that in active control group (P < 0.0001). In terms of safety, sparsentan is generally well tolerated, consistent with the safety characteristics observed so far. According to the results of the interim analysis, the company plans to use the accelerated approval channel to submit new drug applications in the first half of 2022.
Sparcentan is an endothelin / angiotensin receptor antagonist (deara) with dual mechanisms. Preclinical data show that it can reduce proteinuria, protect podocytes and prevent glomerulosclerosis and mesangial cell proliferation by blocking the type 1 pathway of endothelin A and angiotensin II. IgA nephropathy is a rare renal disease, which often leads to end-stage renal disease. In several chronic kidney diseases (such as IgA nephropathy), the combination of endothelin receptor and angiotensin receptor blocker, angiotensin converting enzyme inhibitor or renin angiotensin blocker has a stronger therapeutic effect on proteinuria.
404 adult IgAN patients were enrolled in the ongoing randomized, double-blind, parallel grouping, active control and multicenter clinical trial protect. These patients continued to develop proteinuria despite active drug treatment. In the trial, patients were randomly treated with 400 mg sparsentan once daily or active control drug in a ratio of 1:1. After 36 weeks, the proteinuria of sparsentan group (n = 280) decreased by 49.8% and that of active control group decreased by 15.1% (P < 0.0001).
The preliminary analysis of the medium-term safety results shows that so far, the two treatment groups are generally well tolerated in the study, sparsentan is consistent with the previously observed safety characteristics, and there are no new safety signals.
Sparcentan is also currently conducting a key phase 3 clinical trial for the treatment of focal segmental glomerulosclerosis (FSGS). The press release pointed out that if both indications are approved, sparsentan may be the first drug approved for FSGS and IgAN at the same time.
