Ligand Partner Travere Therapeutics Receives Full FDA Approval for FILSPARI® (sparsentan) in FSGS

FDA approves expanded indication making FILSPARI available to patients with IgA nephropathy (IgAN) at risk of progression; updated label includes data showing long-term durable benefit on proteinuria and kidney function preservation that accrued over two years

Conversion to full approval based on results from the PROTECT Study, where FILSPARI delivered superior long-term kidney function preservation compared to the active comparator irbesartan in the only Phase 3 head-to-head trial conducted in IgAN

As an oral, non-immunosuppressive and dual acting, once-daily medicine with superior long-term results vs. irbesartan, FILSPARI has the potential to become foundational care in IgAN

Ligand is entitled to a 9% royalty on worldwide net sales of FILSPARI

JUPITER, Fla.--(BUSINESS WIRE)-- Ligand Pharmaceuticals Incorporated (Nasdaq: LGND) today announced that its partner Travere Therapeutics, Inc. (Nasdaq: TVTX) has received full approval from the U.S. Food and Drug Administration (FDA) for FILSPARI® (sparsentan) to slow kidney function decline in adults with primary IgAN who are at risk of disease progression. Ligand is entitled to milestone payments and a 9% royalty on worldwide net sales of FILSPARI.

FILSPARI was granted accelerated approval in February 2023 based on the surrogate marker of proteinuria. Full approval is based on positive long-term confirmatory results from the PROTECT Study demonstrating that FILSPARI significantly slowed kidney function decline over two years compared to irbesartan.

“This announcement is a momentous milestone for Travere and a positive development for people living with this rare kidney disease,” said Todd Davis, CEO of Ligand. “We are encouraged by Travere’s progress to drive adoption of FILSPARI in the U.S. and look forward to the European launch over the coming months. FILSPARI is a core part of Ligand’s commercial-stage royalty portfolio, and we believe this treatment will be a significant driver of revenue for us over the next several years.”

FILSPARI is the only oral, once-daily, non-immunosuppressive medication that directly targets glomerular injury in the kidney by blocking two critical pathways of IgAN disease progression (endothelin-1 and angiotensin II).

The two-year efficacy data contained in the FDA-approved label is a modified intention to treat (ITT) analysis, and as preferred by the FDA, evaluates data from all patients regardless of treatment discontinuation. In the final analysis of the 404 randomized patients, FILSPARI significantly reduced the rate of decline in kidney function from baseline to Week 110 compared to 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 FILSPARI 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=0.0168). The positive treatment effects on proteinuria compared to the active control irbesartan that were observed at Week 36 were durable out to the two-year measurement period. Additional results from the PROTECT Study demonstrated the benefit of FILSPARI 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 FILSPARI and irbesartan.

Results from the PROTECT Study showed that FILSPARI was well tolerated with a clearly defined safety profile that has been consistent across all clinical trials conducted to date. Following engagement with the FDA, the Company expects to submit an sNDA for a potential modification to the liver-monitoring REMS.

About IgA Nephropathy

IgA nephropathy (IgAN), also called Berger's disease, is a rare progressive kidney disease characterized by the buildup of immunoglobulin A (IgA), a protein that helps the body fight infections, in the kidneys. The deposits of IgA cause a breakdown of the normal filtering mechanisms in the kidney, leading to blood in the urine (hematuria), protein in the urine (proteinuria) and a progressive loss of kidney function. Other symptoms of IgAN may include swelling (edema) and high blood pressure.

IgAN is the most common type of primary glomerulonephritis worldwide and a leading cause of kidney failure due to glomerular disease. IgAN is estimated to affect up to 150,000 people in the U.S. and is one of the most common glomerular diseases in Europe and Japan.

About the PROTECT Study

The PROTECT Study is one of the largest interventional studies to date in IgA nephropathy (IgAN) and the only Phase 3 head-to-head trial in this rare kidney disease. It is a global, randomized, multicenter, double-blind, parallel-arm, active-controlled clinical trial evaluating the safety and efficacy of 400 mg of FILSPARI (sparsentan), compared to 300 mg of irbesartan, in 404 patients ages 18 years and up with IgAN and persistent proteinuria despite receiving at least 50% of max label dose and maximally tolerated ACE or ARB therapy.

The primary efficacy endpoint for the interim analysis was the change from baseline in urine protein/creatinine ratio at Week 36. The key secondary efficacy endpoint for the final analysis was the rate of change in eGFR over a 110-week period following initiation of randomized therapy.

The trial met the pre-specified primary endpoint which showed that after 36 weeks patients receiving FILSPARI achieved a mean reduction in proteinuria from baseline of 49.8%, compared to a mean reduction in proteinuria from baseline of 15.1% for irbesartan-treated patients (p