FDA Approves Sparsentan to Reduce Proteinuria in Focal Segmental Glomerulosclerosis

The FDA granted approval for sparsentan (Filspari) to reduce proteinuria in adult and pediatric patients 8 years and older with focal segmental glomerulosclerosis (FSGS) who do not have nephrotic syndrome. This decision marks a historic milestone as sparsentan becomes the first and only medication specifically approved for this rare and devastating condition, which was previously managed with off-label therapies such as long-term steroids.¹

“Today marks a historic milestone for people living with FSGS, who for the first time have an FDA-approved medicine for this rare and devastating condition,” Eric Dube, PhD, president and CEO of Travere Therapeutics, said in the news release. “This approval reflects years of perseverance and our belief that those living with FSGS deserve better.”

FSGS is characterized by progressive scarring of the kidney's filtering units, known as glomeruli, which often results in permanent kidney failure requiring dialysis or transplant. The approval specifically targets a population of more than 30,000 individuals in the United States who have FSGS without active nephrotic syndrome, defined as the concurrent presence of high proteinuria, edema, and low serum albumin.^1,2

The approval is supported by data from the phase 3 DUPLEX (NCT03493685) study, which stands as the largest head-to-head interventional trial conducted in the FSGS population. In this global, randomized, double-blind study involving 371 patients, researchers compared the efficacy and safety of sparsentan with the active control irbesartan over a 108-week period.³

Although the primary end point of the rate of change in estimated glomerular filtration rate did not show a statistically significant difference between the 2 groups in the overall study population, sparsentan demonstrated a superior ability to reduce proteinuria. Patients without nephrotic syndrome who were treated with sparsentan experienced a 48% reduction in proteinuria from baseline to week 108 compared with a 27% reduction for those in the irbesartan group. Furthermore, these patients showed a clinical benefit in kidney function preservation with a treatment difference in mean change from baseline in estimated glomerular filtration rate of 1.1 mL/min/1.73 m² compared to the control group.

For pharmacists, understanding the unique pharmacology of sparsentan is essential, as it represents a first-in-class dual endothelin-angiotensin receptor antagonist. The medication targets both endothelin receptor type A and angiotensin II receptor type 1, pathways that are believed to drive the inflammation and scarring processes in the kidney. By simultaneously blocking these receptors, sparsentan is designed to protect the glomeruli from further damage and slow the decline of kidney function. The safety profile observed in the DUPLEX study was comparable with irbesartan, with common adverse reactions including peripheral edema, hypotension, hyperkalemia, dizziness, and anemia.^3,4

Clinical management of sparsentan requires strict adherence to a Risk Evaluation and Mitigation Strategy, known as the Filspari REMS program, due to the risks of hepatotoxicity and embryo-fetal toxicity. Because some endothelin receptor antagonists have been linked to liver failure, providers must measure transaminases and bilirubin before starting treatment and continue monitoring these levels every 3 months. Additionally, the drug is contraindicated during pregnancy as it may cause fetal harm, necessitating pregnancy testing before initiation and monthly thereafter for patients who can become pregnant. Pharmacists must ensure that both the prescriber and the pharmacy are enrolled in the REMS program before dispensing the medication.¹

“For decades, treatment options have been limited, often relying on off-label therapies such as long-term steroids that can carry a significant burden for patients. In the DUPLEX Study, Filspari delivered rapid and sustained reductions in proteinuria compared to irbesartan, with particularly meaningful effects in patients without nephrotic syndrome,” Kirk Campbell, M.D., president of the National Kidney Foundation and the C. Mahlon Kline Professor and chief of the Division of Renal-Electrolyte and Hypertension in the Perelman School of Medicine at the University of Pennsylvania, said in the news release. “This is consistent with KDIGO guidance, which emphasize reducing proteinuria as a key strategy to slow disease progression in FSGS.”

The introduction of sparsentan provides a foundational standard of care where none previously existed, aligning with clinical practice guidelines that emphasize proteinuria reduction as a key strategy for managing glomerular diseases. This approval represents a significant shift in the treatment landscape for FSGS, offering a targeted therapeutic option for a patient community that has long faced clinical uncertainty.

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REFERENCES

1. Travere Therapeutics announces full FDA approval of Filspari (sparsentan), the first and only approves medicine for FSGS. News release. Travere Therapeutics. April 13, 2026. Accessed April 14, 2026. https://ir.travere.com/press-releases/news-details/2026/Travere-Therapeutics-Announces-Full-FDA-Approval-of-FILSPARI-sparsentan-the-First-and-Only-Approved-Medicine-for-FSGS/default.aspx

2. Mayo Clinic. Focal segmental glomerulosclerosis (FSGS). January 31, 2025. Accessed April 14, 2026. https://www.mayoclinic.org/diseases-conditions/fsgs/symptoms-causes/syc-20354693

3. Chen Z, Bai J, Niu L. Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis. N Engl J Med. 2024;390(12):1154. doi:10.1056/NEJMc2401126

4. Mayo Clinic. Sparsentan (oral route). Updated April 1, 2026. Accessed April 14, 2026. https://www.mayoclinic.org/drugs-supplements/sparsentan-oral-route/description/drg-20544734