Travere Therapeutics has announced plans to pursue expanded approval for FILSPARI® (sparsentan) following a successful Type C meeting with the U.S. Food and Drug Administration. The company aims to submit a supplemental New Drug Application (sNDA) by the end of the first quarter of 2025, seeking traditional approval for treating focal segmental glomerulosclerosis (FSGS).
The submission represents a significant milestone in addressing an unmet medical need, as there are currently no FDA-approved treatments specifically indicated for FSGS, a rare kidney disorder affecting more than 40,000 adults and children in the United States.
"Treatment options for FSGS are desperately needed," said Eric Dube, Ph.D., president and chief executive officer of Travere Therapeutics. "The DUPLEX and DUET studies, two of the largest interventional studies conducted to-date in FSGS, will serve as the basis for our submission."
Clinical Evidence and Study Results
The sNDA will be supported by data from both the Phase 3 DUPLEX study and the Phase 2 DUET study. The DUPLEX study, notably the largest interventional study conducted in FSGS to date, demonstrated significant proteinuria reduction and higher rates of partial and complete remission at 108 weeks compared to the active control. While it did not meet its primary efficacy endpoint for estimated glomerular filtration rate (eGFR) slope over 108 weeks, the study showed a lower rate of end-stage kidney disease compared to the control group.
The Phase 2 DUET study met its primary efficacy endpoint, showing a greater than two-fold reduction in proteinuria compared to irbesartan. Importantly, sparsentan demonstrated a favorable safety profile across all clinical trials, comparable to the active control, with no reported cases of drug-induced liver injury or fluid overload.
PARASOL Findings Support Application
The timing of the submission aligns with recent findings from the PARASOL (Proteinuria and GFR as Clinical Trial Endpoints in FSGS) workgroup, which provided crucial support for the use of proteinuria as a meaningful endpoint in FSGS clinical trials. The workgroup's analysis revealed that reduction in proteinuria over 24 months strongly correlates with a decreased risk of kidney failure.
Disease Impact and Clinical Significance
FSGS is characterized by progressive scarring of the kidney's filtering units, leading to protein leakage into the urine (proteinuria). This protein leakage is considered toxic to other parts of the kidney, particularly the tubules, potentially accelerating disease progression. Common symptoms include edema, low blood albumin levels, abnormal lipid profiles, and hypertension.
If approved, FILSPARI would represent a significant advancement in FSGS treatment, offering hope to patients who currently have limited therapeutic options. The drug has already received approval for slowing kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression.
The company plans to work closely with the FDA throughout the review process, maintaining their commitment to addressing the critical needs of patients with rare kidney disorders.
