FDA Accepts Sparsentan (Filspari) sNDA for Focal Segmental Glomerulosclerosis

The US Food and Drug Administration has accepted Travere Therapeutics’ supplemental New Drug Application (sNDA) for traditional approval of sparsentan (Filspari) for the treatment of focal segmental glomerulosclerosis (FSGS).1

According to a May 15, 2025, press release from Travere, the submission is supported by results from the phase 3 DUPLEX Study and the phase 2 DUET Study, 2 of the largest head-to-head interventional studies conducted to date in adult and pediatric patients with FSGS. With the acceptance, the FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of January 13, 2026, and has indicated that it is currently planning to hold an advisory committee meeting to discuss the application.1

“Today marks an important milestone in our mission to transform care for patients with rare kidney disease. We are one step closer to potentially delivering the first approved treatment for people living with FSGS — a leading cause of kidney failure and devastating condition that urgently needs new treatment options,” said Eric Dube, PhD, president and chief executive officer of Travere Therapeutics.1 “With this progress, we continue our commitment to the FSGS community who has been waiting so long for an effective medicine. We look forward to the upcoming review process.”

The acceptance comes nearly 2 months after Travere announced the submission of an sNDA seeking priority review for traditional approval for FSGS.2

Sparsentan is a non-immunosuppressive, oral medication that directly targets podocyte injury by selectively blocking the endothelin A receptor (ETAR) and the angiotensin II subtype 1 receptor (AT1R). Its initial approval came in 2023 in the form of accelerated approval for the reduction of proteinuria in IgA nephropathy, with this expanded to a full approval in September 2024—making the once-daily, oral medication the first non-immunosuppressive treatment for preventing the function of kidney decline in IgA nephropathy.2

The Phase 3 DUPLEX study is the largest interventional study to date in FSGS, and the only study in FSGS against a maximally dosed active comparator. Of note, while DUPLEX achieved its pre-specified interim FSGS partial remission of proteinuria endpoint with statistical significance at 36 weeks, it did not achieve the primary efficacy eGFR slope endpoint over 108 weeks of treatment. The 2-year results from the study were published in the New England Journal of Medicine and showed that sparsentan delivered clinically meaningful benefit at 108 weeks with significant proteinuria reduction, higher rates of partial and complete remission, and a lower rate of end-stage kidney disease compared to the active control.1

The phase 2 DUET Study of sparsentan in FSGS met the primary efficacy endpoint for the combined treatment group, demonstrating a greater than 2-fold reduction in proteinuria compared to irbesartan. Additionally, sparsentan was well-tolerated with a safety profile that was consistent across all clinical trials conducted to date and comparable to the maximally dosed active control, irbesartan, including no drug-induced liver injury and no fluid overload.1

Of note, the results from DUPLEX and DUET are in alignment with the recent findings of the PARASOL workgroup that support the importance of proteinuria in FSGS. The principal finding from PARASOL was that in FSGS, reduction in proteinuria over 24 months is strongly associated with a reduction in the risk of kidney failure, and responder definitions based on thresholds of proteinuria are both biologically plausible and strongly supported by epidemiological data.1

References

1. Travere Therapeutics. Travere Therapeutics Announces FDA Acceptance of sNDA for FILSPARI® (sparsentan) in FSGS. May 15, 2025. Accessed May 15, 2025. https://ir.travere.com/press-releases/news-details/2025/Travere-Therapeutics-Announces-FDA-Acceptance-of-sNDA-for-FILSPARI-sparsentan-in-FSGS/default.aspx

2. Brooks A. Travere Therapeutics Submits sNDA for Sparsentan (Filspari) in FSGS. March 17, 2025. Accessed May 15, 2025. https://www.hcplive.com/view/travere-therapeutics-submits-snda-sparsentan-filspari-fsgs