Travere Therapeutics Plans FSGS Submission for Sparsentan

Michelle Rheault, MD
Credit: University of Minnesota

Travere Therapeutics has announced its intent to submit a supplemental New Drug Application (sNDA) for sparsentan (Filspari) with the US Food and Drug Administration (FDA) for the treatment of focal segmental glomerulosclerosis (FSGS).

The announcement, which was made on February 11, 2025, comes after the completion of a Type C meeting with the FDA and discloses the company’s intent to submit around the end of Q1 2025, with the sNDA based on existing data from the phase 3 DUPLEX and phase 2 DUET studies.¹

“We are pleased with the outcome of our Type C meeting and to be moving forward with an sNDA submission to add a potential FSGS indication for FILSPARI in the U.S. Treatment options for FSGS are desperately needed as there are currently no approved medicines indicated for this devastating, progressive and complex rare kidney disorder that affects more than 40,000 adults and children in the US,” said Eric Dube, PhD, president and chief executive officer of Travere Therapeutics.¹ “The DUPLEX and DUET studies, two of the largest interventional studies conducted to-date in FSGS, will serve as the basis for our submission. Importantly, the results from these studies are in alignment with the recent findings of the PARASOL workgroup that support the importance of proteinuria in FSGS.”

In recent years, the management of rare kidney diseases has been undergoing a renaissance. Though the primary target for early development has been IgA nephropathy, many companies have shifted focus to other forms of glomerular disease, such as FSGS and C3 glomerulopathy. Sparsentan’s first 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.^1,2

Between these 2 approvals in IgA nephropathy, results of the DUPLEX trial were celebrated upon their debut at the American Society of Nephrology’s Kidney Week 2023. Presented at the meeting by Michelle Rheault, MD, a pediatric nephrologist and professor of pediatrics at the University of Minnesota, DUPLEX was billed as the largest interventional study in FSGS to date and compared the use of sparsentan against irbesartan among 371 patients for 108 weeks.^1,3

“I think, for a patient with FSGS, they're at such high alert for that next stage the disease that anything that we can offer them that might slow that down is really going to be of benefit,” Rheault told HCPLive Nephrology in an interview at Kidney Week 2023.³

A global, multicenter, randomized, double-blind, parallel-group, active-controlled study, inclusion criteria required patients to be 8 to 75 years age, have biopsy-confirmed FSGS or a documented pathogenic variant in a podocyte protein associated with FSGS, a urinary protein-to-creatinine ratio of 1.5 or greater, and an eGFR of at least 30 mL/min/1.73m2 of body-surface area at screening.^1,3

At week 108, there were no significant differences in eGFR slope between those receiving sparsentan and irbesartan. However, investigators highlighted a total slope difference from day 1 to week 108 of 0.3 mL/min/1.73 m² per year (95% CI, −1.7 to 2.4) and a chronic slope difference from week 6 to week 108 of 0.9 mL/min/1.73 m² per year (95% CI, −1.3 to 3.0). Additionally, at week 112, the mean eGFR decline was −10.4 mL/min/1.73 m² with sparsentan and −12.1 mL/min/1.73 m² with irbesartan, resulting in a non-significant difference of 1.8 mL/min/1.73 m² (95% CI, −1.4 to 4.9).^1,3

In the aforementioned interview, Rheault explained her interpretation of study results, including the lack of statistical significance.

“Because FSGS is such a rare disease, it's challenging to have enough patients in the clinical trials in order to show that kind of statistically significant reduction in event rates, like end-stage kidney disease. For some of the chronic kidney disease trials, you might have 5000 to 7000 patients enrolled. In our study, there was 370 patients and that was already the biggest trial ever done in FSGS,” Rheault explained.³ “So, we probably are never going to have a study that shows those event rates to be reduced, but we showed an effect on things intended to predict the development of end-stage kidney disease.”

References:

1. Travere Therapeutics, Inc. Travere Therapeutics to submit sNDA for Filspari® (sparsentan) in FSGS. Travere Therapeutics, Inc. February 11, 2025. Accessed February 11, 2025. https://ir.travere.com/news-releases/news-release-details/travere-therapeutics-submit-snda-filsparir-sparsentan-fsgs.

2. Brooks A. FDA approves Travere Therapeutics’ Sparsentan to slow kidney function decline in adult primary IgAN. HCP Live. September 7, 2024. Accessed February 11, 2025. https://www.hcplive.com/view/fda-approves-travere-therapuetics-sparsentan-for-proteinuria-reduction-in-adult-primary-igan.

3. Campbell P. Understanding the duplex trial and Sparsentan in FSGS, with Michelle Rheault, MD. HCP Live. November 5, 2023. Accessed February 11, 2025. https://www.hcplive.com/view/understanding-the-duplex-trial-and-sparsentan-in-fsgs-with-michelle-rheault-md.