Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

Novel drugs approved by the EMA, the FDA, and the MHRA in 2023: A year in review

“…This is the very first time that a therapy relying on CRISPR/Cas9 editing reaches clinical approval, creating a therapeutic landmark; however, patients will be monitored for >10 years for adverse effects including haematopoetic malignacies. and a safety profile similar to that of irbesartan (Rovin et al, 2023).…”

Endothelin System in Hypertension and Chronic Kidney Disease

“…However, because of side effects, their potential usefulness in hypertension, heart failure, atherosclerosis, CKD, diabetes, and other diseases is only now reaching the clinic with new ET antagonists with fewer side effects. The approved indications to date of ET blockade are, for many years, primary pulmonary hypertension and, recently, IgAN following the PROTECT trial 61,62 (in this case with the ET A /AT 1 receptor blocker sparsentan), and the use of the dual ET A R/ET B R blocker bosentan in patients with scleroderma with digital ulcers. 79 However, there are promising results for the treatment of hypertension, and potentially in difficult-to-control and resistant hypertension with dual ET A R and ET B R antagonists, 54 that augur well for the arrival of these agents to the clinic for the treatment of hypertension and potentially in different forms of CKD such as diabetic kidney disease and focal segmental glomerulosclerosis, 64 and interestingly, taking advantage of the ability of these agents to reduce pain in patients with CKD.…”

“…Once-daily treatment with sparsentan produced a meaningful reduction in proteinuria compared with irbesartan in adults with IgAN, with similar safety to irbesartan. In the recently published extension of the PRO-TECT trial, 62 patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group, and the significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period. At 110 weeks, proteinuria was 40% lower in the sparsentan group than in the irbesartan group.…”

Histological reappraisal of IgA nephropathy: the role of glomerular pattern of injury and mesangial complement deposition

“…While the Oxford Classification of IgAN has been originally developed in 2009, little progress has been made in the past decade regarding the histologic stratification of these patients [ 23 ]. This should be interpreted in the context of the significant progress made in the understanding of IgAN pathogenesis that led to the development of several new agents targeting various pathogenic pathways: the dual endothelin-angiotensin receptor blocker sparsentan, TRF-budesonide, inhibitors of B-cell activating factors or anti-complement therapies [ 12 , 13 , 15 , 24 , 25 ]. Accordingly, the “ one-size-fits-all ” treatment selection based on eGFR and proteinuria does not fulfill the needs of patients with IgAN as neither renal function nor proteinuria cannot accurately differentiate between histologic activity or chronicity, or between the need of more intensified optimized supportive care (with the addition of SGLT2 inhibitors or sparsentan) or of more intensified IS treatment.…”