FDA Approves REMS Modification for Sparsentan in IgA Nephropathy

The FDA approved updated Risk Evaluation and Mitigation Strategy (REMS) labeling for sparsentan (Filspari; Travere Therapeutics), a treatment for immunoglobulin A (IgA) nephropathy (IgAN). With this update, the frequency of liver function monitoring is reduced to every 3 months from the onset of treatment with sparsentan, and the embryo-fetal toxicity monitoring requirement is removed from the REMS, wrote the manufacturers in a news release.¹

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IgAN nephropathy—also known as Berger disease—is a rare and progressive kidney disease that is characterized by the buildup of IgA, a protein that aids the body when fighting off infections within the kidney. If left untreated or unmanaged, IgAN can cause a breakdown of the kidney’s normal filtering mechanisms, leading to hematuria, proteinuria, chronic kidney disease (CKD), or other progressive loss of kidney function. Not only is IgAN a potential cause of CKD, but it is also a worldwide leading cause of kidney failure—also known as end-stage kidney disease, or the final stage of CKD—related to glomerular disease. Other IgAN symptoms include swelling and hypertension.¹

The manufacturers wrote that this action was supported by safety data from postmarketing in addition to results from the phase 3 PROTECT clinical trial (NCT03762850)², a randomized, multicenter, double-blind, parallel-group, active-control study. Patients were aged 18 years or older with biopsy-proven IgAN and proteinuria of at least 1 g per day for at least 12 weeks. They were randomly assigned to receive either sparsentan (target dose of 400 mg per day; n = 203) or irbesartan (Avapro; Sanofi; target dose of 300 mg per day; n = 203) based on a permuted-block randomization method.^1,2

The trial’s primary end point was proteinuria change between treatment groups at week 36, and secondary end points included rate of change of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure reduction, safety, and tolerability up to 110 weeks following randomization. Thirty-six-week results of this trial were published in Lancet in 2023.^2,3

The findings indicated that patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. Specifically, eGFR chronic 2-year slopes (weeks 6–110) were about –2.7 mL/min/1.73 m² per year compared with –3.8 mL/min/1.73 m² per year (difference: 1.1 mL/min/1.73 m² per year [95% CI 0.1 to 2.1; p = .037]) in these respective groups. The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period, and at 110 weeks, proteinuria was approximately 40% lower in the sparsentan group (–42.8% [95% CI –49.8 to –35.0]) than in the irbesartan group (–4.4% [95% CI –15.8 to 8.7]). Further, the composite kidney failure end point was reached by approximately 9% (n = 18) and 13% (n = 26) of patients treated with sparsentan and irbesartan (relative risk: 0.7 [95% CI 0.4 to 1.2]). Treatment-emergent adverse events were shown to be well balanced between the 2 groups, with no new safety signals observed by the investigators.³

Sparsentan is indicated to slow the decline of kidney function in adults with IgAN who are at risk for disease progression. According to the manufacturers, it is the first and only nonimmunosuppressive, single-molecule, endothelin-1 and angiotensin II receptor antagonist that binds to the endothelin type A receptor and angiotensin II type 1 receptor.^1,4

The manufacturers report that a supplemental new drug application for sparsentan in focal segmental glomerulosclerosis (FSGS) is currently under review with the FDA, with a Prescription Drug User Fee Act (PDUFA) target action date of January 13, 2026. If approved, sparsentan would be the first and only approved medicine indicated for FSGS.

“[Sparsentan] is becoming a foundational treatment for people living with IgA nephropathy, giving patients and their families hope for slowing the progression of their disease,” Jula Inrig, MD, chief medical officer of Travere Therapeutics, said in a news release. “Today’s approval of streamlined monitoring requirements reflects the strong safety profile of [sparsentan] established to date across clinical and real-world use, simplifying access for patients.”¹

REFERENCES

1. Businesswire. Travere Therapeutics Announces U.S. FDA Approves REMS Modification for FILSPARI® (sparsentan) in IgA Nephropathy. News release. August 27, 2025. Accessed August 28, 2025. https://www.businesswire.com/news/home/20250827211581/en/Travere-Therapeutics-Announces-U.S.-FDA-Approves-REMS-Modification-for-FILSPARI-sparsentan-in-IgA-Nephropathy

2. A Study of the Effect and Safety of Sparsentan in the Treatment of Patients With IgA Nephropathy (PROTECT). ClinicalTrials.gov identifier: NCT03762850. Updated June 10, 2025. Accessed August 28, 2025. http://clinicaltrials.gov/study/NCT03762850

3. Rovin BH, Barratt J, Heerspink HJL, et al. Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial. Lancet. 2023;402(10417):2077-2090. doi:10.1016/S0140-6736(23)02302-4

4. FILSPARI® (sparsentan). Mechanism of Disease. Accessed August 28, 2025. https://filsparihcp.com/igan/FILSPARI-mechanism/