Travere Therapeutics Provides Regulatory Updates on its Development Programs

PDUFA target action date for NDA for sparsentan in IgAN on-track for November 17, 2022

Company to utilize traditional approval process for sparsentan in FSGS following completion of the pivotal Phase 3 DUPLEX Study in 2023

Company and its partner Vifor Pharma applying for conditional marketing authorization of sparsentan for IgAN in Europe; review decision expected in second half of 2023

Pegtibatinase granted Breakthrough Therapy Designation by FDA

Company to host conference call and webcast tomorrow at 8:00 a.m. ET

SAN DIEGO, Aug. 03, 2022 (GLOBE NEWSWIRE) -- Travere Therapeutics, Inc. (NASDAQ: TVTX) today provided regulatory updates for its sparsentan programs in IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS), as well as its pegtibatinase program for classical homocystinuria (HCU).

Sparsentan NDA for accelerated approval in IgAN on-track for PDUFA target action date of November 17, 2022

The Company recently completed a mid-cycle review meeting with the U.S. Food and Drug Administration (FDA) for its New Drug Application (NDA) currently under priority review for accelerated approval of sparsentan for the treatment of IgAN. The FDA indicated that the NDA review process is proceeding as planned with no advisory committee meeting expected and that it remains on-track for the previously assigned Prescription Drug User Fee Act (PDUFA) target action date of November 17, 2022.

Following FDA feedback on the ongoing pivotal Phase 3 DUPLEX Study, Company planning to pursue traditional approval of sparsentan for FSGS in 2023

The Company also completed its planned Type A meeting with the FDA to discuss a potential submission for accelerated approval of sparsentan for FSGS. In recently received final meeting minutes, the FDA acknowledged the high unmet need for approved therapies as well as the challenges in studying FSGS but indicated that the interim analysis from the ongoing pivotal Phase 3 DUPLEX Study conducted in 2021 together with the recent limited additional estimated glomerular filtration (eGFR) data-cut do not meet their threshold to support an application for accelerated approval in FSGS, which would be the first accelerated approval in FSGS. The FDA indicated that the DUPLEX Study as designed maintains the potential for full approval pending completion of the study and recommends that the Company pursue traditional approval based on two-year eGFR slope. The Company anticipates having topline data from the DUPLEX Study, including full two-year eGFR data, in the first half of 2023 and to be in position to submit an NDA for full approval in the second half of the year.

“Our goal is to enable sparsentan to become a new treatment standard for rare kidney disorders, and we believe we are well-positioned for the first potential approval of sparsentan in IgA nephropathy in November of this year,” said Eric Dube, Ph.D., president and chief executive officer of Travere Therapeutics. “While we are disappointed that we will not be filing for accelerated approval of sparsentan in FSGS, the eGFR data in the DUPLEX Study have continued to progress in a manner consistent with the profile of sparsentan and we remain confident that the study can support an application for full approval in FSGS next year. We look forward to continuing to work with the FDA throughout the ongoing review of our NDA for accelerated approval of sparsentan in IgA nephropathy and as we prepare for an NDA submission for FSGS next year.”

The Company and its partner Vifor Pharma are applying for conditional marketing authorisation of sparsentan for the treatment of IgAN in Europe

The Company and its partner Vifor Pharma are submitting a Conditional Marketing Authorisation (CMA) application for sparsentan for the treatment of IgAN in Europe. A review decision on a potential approval is expected in the second half of 2023. Pending completion of the DUPLEX Study and data supportive of approval, a subsequent CMA variation of sparsentan for the treatment of FSGS is targeted for submission by the end of 2023.

Pegtibatinase granted Breakthrough Therapy Designation for HCU

The FDA recently granted Breakthrough Therapy Designation to pegtibatinase, the Company’s novel investigational enzyme replacement therapy being evaluated for the treatment of HCU.

The Breakthrough Therapy Designation is supported by data from the ongoing Phase 1/2 COMPOSE Study of pegtibatinase in patients with HCU, as well as data from the Company’s ongoing natural history study. In the COMPOSE Study, treatment with 1.5mg/kg, twice weekly doses of pegtibatinase resulted in rapid and sustained reductions in total homocysteine (tHcy) through 12 weeks of treatment, including a 55.1% mean relative reduction in tHcy from baseline as well as maintenance of tHcy below a clinically meaningful threshold of 100 μmol. As of the data cut-off, pegtibatinase has been generally well-tolerated.

“Many people living with HCU are unable to adequately control toxic homocysteine levels with the limited available treatment options. As a result, they are living at high risk of developing long-term, serious complications from disease progression,” said Bill Rote, Ph.D., senior vice president of research and development at Travere Therapeutics. “Receiving Breakthrough Therapy Designation is a significant step forward in the development of our program and we look forward to continuing to work closely with the FDA as we seek to align on a pivotal Phase 3 program that will ultimately position pegtibatinase to potentially become the first disease-modifying therapy for HCU.”

Breakthrough Therapy Designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies on a clinically significant endpoint(s). Drugs that receive Breakthrough Therapy Designation are eligible for Fast Track designation features, intensive guidance on an efficient drug development program, and organizational commitment from the FDA.

The Company will report second quarter 2022 financial results tomorrow, Thursday, August 4, 2022, and host a conference call and webcast to discuss corporate updates and financial results at 8:00 a.m. ET.

About Sparsentan

Sparsentan, a Dual Endothelin Angiotensin Receptor Antagonist (DEARA), is a novel investigational product candidate selectively targeting the endothelin A receptor (ETAR) and the angiotensin II subtype 1 receptor (AT1R). Pre-clinical data have shown that blockade of both endothelin type A and angiotensin II type 1 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. In February 2021, the Company announced that the ongoing pivotal Phase 3 DUPLEX Study of sparsentan in FSGS achieved its pre-specified interim FSGS partial remission of proteinuria endpoint (FPRE) 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. In August of 2021, the Company announced that the ongoing PROTECT Study in IgAN met its pre-specified interim primary efficacy endpoint with statistical significance, demonstrating a greater than threefold reduction of proteinuria from baseline after 36 weeks of treatment, compared to the active control irbesartan (p