FDA-Approves first Non-Immunosuppressive Therapy for FSGS

The US Food and Drug Administration has granted full approval to Sparsentan for the treatment of Focal Segmental Glomerulosclerosis, marking the first approved targeted therapy in a condition previously managed mainly with off-label and supportive care.

Sparsentan works via a dual mechanism, blocking both endothelin A and angiotensin II type 1 receptors, thereby directly addressing podocyte injury without the need for immunosuppression. This novel approach helps reduce proteinuria and offers a significant advancement in FSGS management.

FILSPARI is the first and only medicine approved by the FDA for the treatment of FSGS, marking its expansion beyond IgA nephropathy (IgAN) into a second rare kidney disease. FILSPARI is currently the most commonly prescribed FDA-approved medicine for IgAN.

People with FSGS who do not have nephrotic syndrome span across types of FSGS and represent a population aligned with the KDIGO guidelines for treating glomerular diseases. Nephrotic syndrome is commonly defined as the presence of three concurrent criteria: proteinuria greater than 3.5 g/24h, edema, and albumin less than 3.0 g/dL. The company estimates that the addressable population in the U.S. is more than 30,000 individuals with FSGS who do not have nephrotic syndrome.

“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,” said Eric Dube, Ph.D., president and chief executive officer of Travere Therapeutics. “This approval reflects years of perseverance and our belief that those living with FSGS deserve better. It also builds on our leadership and progress in rare kidney diseases, expanding FILSPARI’s potential reach to more than 100,000 people in the U.S. with FSGS and IgAN who need better treatment options. FILSPARI will be available for nephrologists to immediately prescribe to individuals with FSGS. We are profoundly grateful to the patients, caregivers, investigators, healthcare providers, regulators and advocates who made this moment possible.”

In the Phase 3 DUPLEX Study, the largest head-to-head interventional study in FSGS to date, patients treated with FILSPARI in the overall study population experienced a statistically significant 46% reduction in proteinuria from baseline to Week 108 compared to 30% for those treated with maximum labeled dose irbesartan (nominal p-value, 0.0299). In patients without nephrotic syndrome, FILSPARI demonstrated even greater improvements compared to maximum labeled dose irbesartan across proteinuria and eGFR. Those without nephrotic syndrome who were treated with FILSPARI experienced a 48% reduction in proteinuria from baseline to Week 108 compared to 27% for those treated with irbesartan, which was statistically significant (nominal p-value, 0.0075). FILSPARI-treated patients without nephrotic syndrome also demonstrated a benefit in eGFR with a treatment difference of 1.1 mL/min/1.73 m2 based on mean change from baseline to Week 108 (-11.3 mL/min/1.73 m2 for FILSPARI compared to -12.4 mL/min/1.73 m2 for maximum labeled dose irbesartan). Across both adult and pediatric patients, FILSPARI was generally well tolerated, with a safety profile comparable to irbesartan and consistent across clinical programs.

In patients without nephrotic syndrome, FSGS is largely driven by stress on the kidney’s glomeruli and the activation of the pathways that cause inflammation and scarring. FILSPARI’s dual mechanism of action addresses these processes by targeting endothelin A and angiotensin II receptors, which are believed to help protect the kidney and reduce damage.

“Today’s approval of FILSPARI provides nephrologists with a new FDA-approved option for patients living with FSGS,” said 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. “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. This is consistent with KDIGO guidance, which emphasize reducing proteinuria as a key strategy to slow disease progression in FSGS. For patients without active nephrotic syndrome, where optimizing foundational therapy is critical, FILSPARI represents an important new option.”

“The approval of FILSPARI as the first medication for people with FSGS is a life-changing moment for patients and families who have waited far too long,” said Josh Tarnoff, chief executive officer of NephCure. “This milestone reflects the strength and perseverance of an extraordinary collective and broad stakeholder community who participated in research, raised awareness and never gave up hope. The pioneering work of the PARASOL project and the countless patients and caregivers who have shared their journeys along the way have helped make this progress possible. It stands as proof that when science and community unite with purpose, we can redefine what’s possible in rare disease care and bring light to those who have long lived in uncertainty.”