Józef Muszyński, Laura Janik, Miłosz Miedziaszczyk, Ilona Idasiak‑Piechocka

Sparsentan – a milestone in the pharmacotherapy of IgA nephropathy

 

2025-03-20

Study object. Sparsentan is a breakthrough drug characterized by an innovative dual mechanism of action that targets endothelin and angiotensin II receptors. Approved first in the US in 2023 and then in the European Union in 2024, it represents a significant advance in the treatment of IgA nephropathy - the most common form of primary glomerulonephritis. The disease represents a major medical challenge, as many as one-fifth of patients can develop chronic kidney failure within a decade. The essence of the condition lies in the abnormal galactosylation of immunoglobulin A, which sets off a cascade of adverse immune events. This process leads to the formation of autoantibodies and the accumulation of immune complexes in the mesangium, which initiates destructive inflammatory processes.Previous therapeutic approaches, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, glucocorticosteroids, SGLT2 inhibitors and immunosuppressive drugs, among others, have been mainly symptomatic and have not always yielded satisfactory results.

Research Objective. The purpose of this study is to detail the pharmacokinetic properties, mechanism of action, clinical efficacy and safety profile of sparsentan in the treatment of IgA nephropathy. In addition, its potential applications in other indications, such as the treatment of hypertension, reduction of proteinuria in FSGS, and other aspects requiring further research are discussed.

Methods. Available publications on sparsentan, DEARA and IgA nephropathy were analyzed, omitting conference abstracts, subjective opinions and papers published more than 10 years. The focus was on studies of the drug’s efficacy, tolerability, safety and potential applications in other diseases.

Results. The review showed that sparsentan effectively reduces proteinuria and improves renal function in patients with IgA nephropathy. Compared to standard treatment, sparsentan offers an advantage due to its complex mechanism of action, which can simultaneously reduce polyuria. The drug has a favorable pharmacokinetic profile and good tolerability.

Conclusions. Sparsentan, thanks to its unique dual mechanism of action and proven efficacy, opens up new therapeutic opportunities in the treatment of IgA nephropathy, reducing the risk of chronic kidney disease. In addition, there are indications for further research into the use of sparsentan in other indications, such as hypertension and focal segmental glomerular sclerosis (FSGS), making it a versatile and promising therapeutic option.

Keywords: DEARA, sparsentan, IgAN, IgA nephropathy.

© Farm Pol, 2024, 80(10): 713–719