FDA Approves Travere Therapeutics’ Sparsentan to Slow Kidney Function Decline in Adult Primary IgAN

The US Food and Drug Administration has granted full approval to Travere Therapeutics’ sparsentan (Filspari) for slowing kidney function decline in adults with primary IgA nephropathy (IgAN) at risk of disease progression.¹

Announced on September 5, 2024, the decision is based on 2-year confirmatory results from the phase 3 PROTECT study, the largest head-to-head interventional study to date in IgAN and the only one to be conducted versus an active comparator. The conversion from accelerated to full approval makes sparsentan the second therapeutic to receive full approval for IgAN, following last year’s approval of Calliditas Therapeutics’ budesonide (Tarpeyo) delayed release capsules.^1,2

"As a physician who has dedicated my career to treating patients with glomerular diseases, I believe the full approval of FILSPARI for IgAN provides us with a critically important tool for patient management,” said Brad Rovin, MD, medical director at The Ohio State University Center for Clinical Research Management, director, Division of Nephrology, and steering committee member for the PROTECT Study, in a statement. “This approval should facilitate patient access to a medication that targets injury directly in the kidney, reduces proteinuria, even to the point of complete remission in some patients, and is more effective than current standard-of-care treatment in preserving kidney function over time. This is a very exciting milestone in the evolution of treating IgAN.”

The endothelin and angiotensin II receptor antagonist was previously granted accelerated approval in February 2023 based on clinically meaningful and statistically significant improvements in proteinuria compared to an active comparator in the phase 3 PROTECT study. A global, randomized, multicenter, double-blind, active-controlled clinical trial, PROTECT evaluated the safety and efficacy of 400 mg of sparsentan compared to 300 mg of irbesartan in 404 patients ≥ 18 years of age with IgAN and persistent proteinuria despite maximally tolerated ACE or ARB therapy.^3,4

The accelerated approval made sparsentan the first and only non-immunosuppressive treatment targeting glomerular injury in the kidney to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression. However, at the time of this approval, it had not yet been established whether sparsentan slowed kidney function decline in patients with IgAN, and its continued approval was contingent upon confirmation of a clinical benefit in PROTECT.^3,4

Topline 2-year confirmatory secondary endpoint results from PROTECT were announced on September 21, 2023, and demonstrated long-term kidney function preservation with sparsentan as well as a clinically meaningful difference in eGFR total (1.0 mL/min/1.73m² per year; P = .058) and chronic (1.1 mL/min/1.73m² per year; P = .037) slope versus irbesartan, although statistical significance was not achieved for eGFR total slope.⁵

Of note, the 2-year efficacy data in the FDA-approved label is a modified intention to treat (ITT) analysis evaluating data from all patients regardless of treatment discontinuation. In the final analysis of the 404 randomized patients, sparsentan significantly reduced the rate of decline in kidney function from baseline to week 110 compared with irbesartan. In the ITT analysis included in the label, the mean eGFR slope from baseline to week 110 was -3.0 mL/min/1.73 m2/year for sparsentan and -4.2 mL/min/1.73 m2/year for irbesartan, corresponding to a statistically significant treatment effect of 1.2 mL/ min/1.73 m2/year (P = .0168).¹

The positive treatment effects on proteinuria compared to the active control irbesartan that were observed at week 36 were durable out to the 2-year measurement period. Additional results from the PROTECT study demonstrated the benefit of sparsentan on absolute eGFR accrued over time and by week 110 resulted in a 3.8 mL/min/1.73 m2 difference in the mean change from baseline between sparsentan and irbesartan.¹

"The expanded indication and full approval of FILSPARI is welcome news for the rare kidney disease community,” said Josh Tarnoff, chief executive officer of NephCure, in a press release.¹ “We have waited a long time for a medicine to slow the irreversible kidney damage from IgAN and appreciate Travere’s leadership in championing new endpoints for IgAN that have spurred significant innovation for this rare kidney disease.”

References

1. ^{Travere Therapeutics Announces Full FDA Approval of FILSPARI® (sparsentan), the Only Non-Immunosuppressive Treatment that Significantly Slows Kidney Function Decline in IgA Nephropathy. Travere Therapeutics. September 5, 2024. https://ir.travere.com/news-releases/news-release-details/travere-therapeutics-announces-full-fda-approval-filsparir. Accessed September 5, 2024.}
2. ^{Brooks A. FDA Awards Full Approval to Budesonide (Tarpeyo) in Treatment of IgA Nephropathy. HCPLive. December 20, 2023. Accessed September 3, 2024. https://www.hcplive.com/view/fda-awards-full-approval-to-budesonide-tarpeyo-in-treatment-of-iga-nephropathy}
3. ^{Travere Therapeutics. Travere Therapeutics Announces FDA Accelerated Approval of FILSPARIᵀᴹ (sparsentan), the First and Only Non-immunosuppressive Therapy for the Reduction of Proteinuria in IgA Nephropathy. February 17, 2023. Accessed September 3, 2024. https://ir.travere.com/news-releases/news-release-details/travere-therapeutics-announces-fda-accelerated-approval}
4. ^{Travere Therapeutics. Travere Therapeutics Submits Supplemental New Drug Application to the U.S. Food and Drug Administration Seeking Full Approval of FILSPARI® (sparsentan) for the Treatment of IgA Nephropathy (IgAN). March 11, 2024. Accessed September 3, 2024. https://ir.travere.com/news-releases/news-release-details/travere-therapeutics-submits-supplemental-new-drug-application}
5. ^{Travere Therapeutics. Travere Therapeutics Announces Confirmatory Data from the Phase 3 PROTECT Study of FILSPARI® Demonstrating Long-Term Kidney Function Preservation in IgA Nephropathy; Narrowly Missing eGFR Total Slope Endpoint versus Active Control, Irbesartan. September 21, 2023. Accessed September 3, 2024. https://ir.travere.com/news-releases/news-release-details/travere-therapeutics-announces-confirmatory-data-phase-3-protect}