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Sparsentan in immunoglobulin A nephropathy: a profile of its use

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Abstract

Sparsentan (FILSPARI®), an oral, dual endothelin and angiotensin receptor antagonist, is an emerging new treatment option for patients with immunoglobulin A (IgA) nephropathy. Sparsentan received accelerated approval in the USA for the treatment of adults with IgA nephropathy who are at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UP/C) ≥ 1.5 g/g, as well as a positive opinion recommending approval in the EU. In the ongoing phase 3 PROTECT trial in adults with IgA nephropathy, sparsentan was associated with favourable antiproteinuric effects, which were maintained over 110 weeks of treatment. The change in UP/C from baseline at week 36 was significantly greater with sparsentan than with irbesartan, an angiotensin receptor blocker. Early results from the 110-week final analysis of PROTECT also suggested that sparsentan may provide long-term benefits in preserving kidney function in patients with IgA nephropathy. Final analyses from the PROTECT trial, including its open-label extension period, are awaited with interest. Sparsentan was generally well tolerated, with its tolerability profile being similar to that of irbesartan. The most common treatment-emergent adverse events with sparsentan included peripheral oedema, hypotension, dizziness and hyperkalaemia. Longer-term data revealed no new safety signals.

Plain Language Summary

Immunoglobulin A (IgA) nephropathy is a serious immune complex-mediated glomerulonephritis, and a leading cause of kidney failure. It is suggested that reducing proteinuria (elevated protein in the urine) is key to slowing kidney disease progression in patients with IgA nephropathy. Sparsentan (FILSPARI®), an oral, dual endothelin and angiotensin receptor antagonist, is the first non-immunosuppressive therapy approved in the USA for IgA nephropathy in adults who are at risk of rapid disease progression, generally a urine protein-to-creatinine ratio ≥ 1.5 g/g, and has been recommended for approval in the EU. In an ongoing phase 3 clinical trial, sparsentan provided greater and durable (up to 110 weeks) antiproteinuric effects than irbesartan, an angiotensin-receptor blocker, in patients with IgA nephropathy. Sparsentan also demonstrated long-term benefits in kidney function preservation. Sparsentan was generally well tolerated, with its tolerability profile being similar to that of irbesartan. Current evidence indicates that sparsentan is an effective emerging treatment option for adults with IgA nephropathy.

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Acknowledgements

The manuscript was reviewed by: F. Locatelli, Department of Nephrology and Dialysis, Alessandro Manzoni Hospital, Lecco, Italy; A. Rajasekaran, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. During the peer review process, Travere Therapeutics, the marketing authorization holder of sparsentan, was offered an opportunity to provide a scientific accuracy review of their data. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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    Young-A Heo & Connie Kang

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Correspondence to Connie Kang.

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Young-A Heo, a salaried employee of Adis International Ltd/Springer Nature and an editor of Drugs & Therapy Perspectives, and Connie Kang, a salaried employee of Adis International Ltd./Springer Nature, were not involved in any publishing decisions for the manuscript and declare no relevant conflicts of interest. All authors contributed to this article and are responsible for its content.

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Heo, YA., Kang, C. Sparsentan in immunoglobulin A nephropathy: a profile of its use. Drugs Ther Perspect 40, 101–108 (2024). https://doi.org/10.1007/s40267-024-01058-9

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