Travere Therapeutics, Inc. (NASDAQ: TVTX) today provided a regulatory update for its sparsentan program in focal segmental glomerulosclerosis (FSGS). Following achievement of the interim proteinuria endpoint in the ongoing Phase 3 DUPLEX Study of sparsentan in FSGS, the Company conducted pre-New Drug Application (NDA) interactions with the U.S. Food and Drug Administration in pursuit of an accelerated approval submission in the U.S., and Marketing Authorization Application (MAA) pre-submission interactions with the European Medicines Agency (EMA) for conditional marketing authorization and accelerated assessment consideration in Europe.

In recently received final pre-NDA meeting minutes, the FDA acknowledged the high unmet need for approved therapies for the treatment of FSGS but indicated the available data from the interim assessment of the DUPLEX Study would not be adequate to support an accelerated approval at this time. Based upon this feedback, the Company no longer expects to submit for accelerated approval for FSGS in the U.S. during the second half of 2021. The FDA has indicated that it may be possible to submit an application for accelerated approval after additional data accrue in the study. Subject to further discussion with the FDA, the Company believes that it may be possible to provide sufficient additional estimated glomerular filtration (eGFR) data from the DUPLEX Study in the first half of 2022. The FDA has encouraged the Company to request a follow-up meeting to further explore this option in greater detail, and a Type A meeting is expected to occur in the third quarter of 2021.   

"We remain very confident in the profile of sparsentan and believe it supports the ability to ultimately become a new treatment standard for FSGS, but we are disappointed that we will not be able to submit for accelerated approval this year and deliver it to patients on our original targeted timeline," said Eric Dube, Ph.D., chief executive officer of Travere Therapeutics. "Based upon our ongoing dialogue with FDA, we believe the eGFR data need to further mature to support our New Drug Application for accelerated approval in this indication. We remain optimistic that we still have a potential opportunity to pursue a path to an accelerated approval submission in the U.S. next year. We look forward to continuing our collaborative discussions with the FDA and providing a further update in the third quarter of this year."

The Company also conducted initial MAA pre-submission interactions with the EMA. In that meeting, the Company received administrative support for proceeding as planned with a conditional marketing authorization submission in the second half of 2021. The agency also provided direction on administrative and regulatory topics, as well as guidance for upcoming discussions with assigned rapporteurs and co-rapporteurs. As a result of these interactions, the Company will continue its preparations for an MAA submission of sparsentan in FSGS and seek confirmation of its plans with the assigned rapporteurs and co-rapporteurs in an upcoming meeting.

About the DUPLEX Study

In February 2021, the Company announced that the ongoing pivotal Phase 3 DUPLEX Study of sparsentan in FSGS achieved its pre-specified interim FPRE endpoint with statistical significance. FPRE is a clinically meaningful endpoint defined as urine protein-to-creatinine ratio (UP/C) ≤1.5 g/g and a >40 percent reduction in UP/C from baseline. After 36 weeks of treatment, 42.0 percent of patients receiving sparsentan achieved FPRE, compared to 26.0 percent of irbesartan-treated patients (p=0.0094). Preliminary results from the interim analysis suggest that at the time of the interim assessment, sparsentan had been generally well-tolerated and shown a comparable safety profile to irbesartan. The DUPLEX Study is fully enrolled with 371 participants and is scheduled to continue as planned on a blinded basis to assess the confirmatory estimated glomerular filtration rate (eGFR) endpoint after 108 weeks of treatment. Topline results from the confirmatory endpoint are expected in the first half of 2023.

About Focal Segmental Glomerulosclerosis

FSGS is a rare proteinuric kidney disorder that is estimated to affect up to 40,000 patients in the U.S. with similar prevalence in Europe. The disorder is defined by progressive scarring of the kidney and often leads to end-stage kidney disease (ESKD). FSGS is characterized by proteinuria, where protein leaks into the urine due to a breakdown of the normal filtration mechanism in the kidney. Once in the urine, protein is considered to be toxic to other parts of the kidney, especially the tubules, and is believed to contribute to further disease progression. Other common symptoms include swelling in parts of the body, known as edema, as well as low blood albumin levels, abnormal lipid profiles and hypertension.

Reduction in proteinuria appears to be beneficial in the treatment of FSGS and may be associated with a decreased risk of progression to ESKD. Achieving FPRE appears to be associated with long-term preservation of renal function in patients with FSGS. FSGS is currently managed with angiotensin receptor blockers, angiotensin converting enzyme inhibitors, steroids or calcineurin inhibitors.

About Sparsentan

Sparsentan is a novel investigational product candidate, that functions as a high affinity dual-acting antagonist of both the endothelin type A and angiotensin II type 1 receptors, in a single molecule. Pre-clinical data have shown that blockade of both pathways in forms of rare chronic kidney disease, reduces proteinuria, protects podocytes and prevents glomerulosclerosis and mesangial cell proliferation. Sparsentan has been granted Orphan Drug Designation for the treatment of FSGS and IgAN in the U.S. and Europe.

Sparsentan is currently being evaluated in the pivotal Phase 3 DUPLEX Study for the treatment of FSGS and the pivotal Phase 3 PROTECT Study for the treatment of IgAN. If approved for both indications, sparsentan could potentially be the first medicine approved for both FSGS and IgAN.

About Travere Therapeutics

At Travere Therapeutics we are in rare for life. We are a biopharmaceutical company that comes together every day to help patients, families and caregivers of all backgrounds as they navigate life with a rare disease. On this path, we know the need for treatment options is urgent - that is why our global team works with the rare disease community to identify, develop and deliver life-changing therapies. In pursuit of this mission, we continuously seek to understand the diverse perspectives of rare patients and to courageously forge new paths to make a difference in their lives and provide hope - today and tomorrow.