Ligand Pharmaceuticals Incorporated announced that its partner Travere Therapeutics, Inc. has received accelerated approval from the U.S. Food and Drug Administration (FDA) for FILSPARI(TM) (sparsentan) to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression, generally a urine protein-to- creatinine ratio (UPCR) >=1.5 g/g. This indication is granted under accelerated approval based on reduction in proteinuria. It has not been established whether FILSPARI slows kidney function decline in patients with IgAN. The continued approval of FILSPARI may be contingent upon confirmation of a clinical benefit in the ongoing Phase 3 PROTECT Study, which is designed to demonstrate whether FILSPARI slows kidney function decline.

Topline results from the two-year confirmatory endpoints in the PROTECT Study are expected by Travere in the fourth quarter of 2023 and are intended to support traditional approval of FILSPARI. FILSPARI, a once-daily oral medication, is designed to selectively target two critical pathways in the disease progression of IgAN (endothelin-1 and angiotensin II) and is the first and only non-immunosuppressive therapy approved for the treatment of this condition. IgAN is a rare kidney disease and a leading cause of kidney failure due to glomerular disease, affecting up to 150,000 people in the U.S., with approximately 30,000 to 50,000 of such patients estimated to be addressable under the indication approved via accelerated approval.

Travere expects FILSPARI to be available beginning the week of February 27, 2023, and has indicated it will be providing a comprehensive patient support program throughout the patient's treatment journey. Under Ligand's license agreement with Travere for sparsentan, Ligand is entitled to receive a net $15.3 million milestone on this FDA approval, other potential milestone payments and net royalties of 9% on future global net product sales of sparsentan. The approval of FILSPARI, granted under the FDA's accelerated approval pathway, is based on clinically meaningful and statistically significant improvements in proteinuria compared to an active comparator in the pivotal and ongoing Phase 3 PROTECT Study, the largest head-to-head interventional study to date in IgAN.

The PROTECT Study is a global, randomized, multicenter, double-blind, active-controlled clinical trial evaluating the safety and efficacy of 400 mg of FILSPARI, compared to 300 mg of irbesartan, in 404 patients ages 18 years and up with IgAN and persistent proteinuria despite maximal tolerated ACE or ARB therapy. In August 2021, Travere announced positive topline interim results that were based on the pre-specified, primary analyses set which showed that after 36 weeks of treatment, 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<0.0001). Per request from the FDA, the efficacy data contained in the FDA-approved label is a post-hoc sensitivity analysis that evaluates the first 281 randomized patients, a subset of the full trial population.

The mean reduction in proteinuria from baseline in the post-hoc sensitivity analysis is 45% for FILSPARI versus 15% for the active control, irbesartan. Both the pre-specified and post-hoc sensitivity analyses have demonstrated that FILSPARI achieves a rapid and sustained reduction in proteinuria, with statistically significant and clinically meaningful improvement compared to the active comparator irbesartan. Per the study protocol, patients continue in a blinded manner in the PROTECT Study to fully assess the treatment effect on eGFR slope over 110 weeks in the confirmatory endpoint analysis.

Results from the confirmatory endpoint analysis are expected in the fourth quarter of 2023. Results from the interim assessment in 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. In PROTECT, the most common adverse reactions (= 5%) are peripheral edema, hypotension (including orthostatic hypotension), dizziness, hyperkalemia, and anemia.

Because of the risks of liver injury and birth defects, FILSPARI is available only through a Risk Evaluation and Mitigation Strategy (REMS) approved by the FDA. Travere announced that together with their collaborator CSL Vifor, they expect a review decision by the European Medicines Agency (EMA) in the second half of 2023 on the potential approval of the Conditional Marketing Authorization (CMA) application for sparsentan for the treatment of IgAN in Europe. Travere expects to report topline results from the two-year confirmatory endpoints in the ongoing Phase 3 DUPLEX Study of sparsentan in focal segmental glomerulosclerosis (FSGS) in the second quarter of 2023.

Pending supportive data, Travere announced an anticipated submission of a supplemental NDA for traditional approval for an FSGS indication in the second half of 2023 and a subsequent variation to the CMA of sparsentan for the treatment of patients with FSGS in Europe is targeted for submission by the end of 2023. Sparsentan has been granted Orphan Drug Designation for the treatment of IgAN and FSGS in the U.S. and Europe.