SAN DIEGO, CA — Travere Therapeutics Inc. (Nasdaq: TVTX) today announced the completion of a successful pre-NDA meeting with the U.S. Food and Drug Administration (FDA) for FILSPARI® (sparsentan) in IgA nephropathy (IgAN). The Company will submit a supplemental New Drug Application (sNDA) in the first quarter of 2024 for conversion of the existing U.S. accelerated approval of FILSPARI to full approval. The Company also completed regulatory engagement on focal segmental glomerulosclerosis (FSGS) in which the FDA communicated that the Phase 3 DUPLEX Study results alone are not sufficient to support an sNDA submission for an FSGS indication for sparsentan. As a result, the Company will be conducting additional analyses of FSGS data with plans to re-engage FDA in 2024, and is implementing a strategic reorganization in Q4 2023 to focus near-term resources on the ongoing FILSPARI launch in IgAN and the advancement of pegtibatinase in classical homocystinuria (HCU).
“Following a successful pre-NDA meeting, we are pleased to be moving forward with our planned sNDA submission for full approval of FILSPARI in IgA nephropathy. Our team has been working diligently to prepare a high-quality application which we expect to submit next quarter,” said Eric Dube, Ph.D., president and chief executive officer of Travere Therapeutics. “Unfortunately, there is uncertainty around a regulatory path forward for FSGS. While we intend to continue to engage with FDA on a way forward for the more than 40,000 people living with FSGS in the U.S., we must at the same time prioritize our operating expenses. As a result, we have made the difficult decision to reduce our workforce to further focus our resources on the FILSPARI launch and clinical development of pegtibatinase; this action is expected to extend our cash runway into 2028. We have not taken this decision lightly and we are grateful to all of our colleagues who have contributed tremendously to furthering our mission and dedication to helping people living with a rare disease. We are committed to supporting our colleagues who are affected through this challenging time.”
Following supportive FDA feedback on the Company’s plan to submit the two-year results from the Phase 3 PROTECT Study in IgAN, Travere to submit sNDA in Q1 2024 for full U.S. approval of FILSPARI in IgAN
The Company recently completed a pre-NDA meeting with the FDA to discuss the confirmatory results from the Phase 3 PROTECT Study and next steps for submission of an sNDA for full approval. The FDA indicated support for the Company’s plan to submit an sNDA for conversion from accelerated approval to full approval and the Company is on-track to submit the sNDA in Q1 2024.
Following engagement with FDA on the two-year results from the Phase 3 DUPLEX Study of sparsentan in FSGS, Company conducting additional analyses of FSGS data
The Company also completed its planned Type C meeting with the FDA to discuss previously reported results from the Phase 3 DUPLEX Study of sparsentan in FSGS. The FDA acknowledged the high unmet need for approved therapies as well as the challenges in studying FSGS but indicated that the two-year results from the Phase 3 DUPLEX Study alone are not sufficient to support an sNDA submission. The FDA acknowledged the work being done by the larger nephrology community to better understand proteinuria and eGFR as endpoints in clinical trials of FSGS and indicated a willingness to continue to engage with the Company on a potential path forward for sparsentan in FSGS following the Company’s consideration of additional evidence. The Company plans to re-engage with the FDA later in 2024.
To further align the Company’s resources on the ongoing FILSPARI launch and its planned Phase 3 program advancing the development of pegtibatinase as the first potential disease-modifying treatment for HCU, Travere is implementing an approximate 20% workforce reduction focused on non-field-based employees. These adjustments are expected to result in an estimated annualized savings of approximately $25 million beginning in 2024, and an estimated non-recurring charge of approximately $12 million to $14 million primarily recognized in the fourth quarter of 2023. Alongside other cost reduction measures planned, the Company now expects operating expenses of less than $400 million in 2024, exclusive of cost of goods sold, depreciation and amortization and expected net milestone payments to be made of approximately $50 million. Together with $634.6 million in cash and cash equivalents as of September 30, 2023, the Company expects to have a cash runway into 2028.
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 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 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. In August 2021, the Company announced the PROTECT Study met its pre-specified interim primary efficacy endpoint with statistical significance. Based on the pre-specified, primary analyses set, after 36 weeks of treatment, patients receiving sparsentan 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). The study’s confirmatory secondary endpoint in the U.S. is estimated glomerular filtration rate (eGFR) total slope from day 1 to week 110 of treatment. The confirmatory secondary endpoint in the EU is eGFR chronic slope from week 6 to week 110 of treatment, following the initial acute effect of randomized treatment. Following the 110-week blinded treatment period, treatment with study medication was discontinued for 4 weeks — at this time, the investigator resumed standard of care treatment. In September 2023, the Company announced topline two-year confirmatory secondary endpoint results from the PROTECT Study of sparsentan in IgAN. FILSPARI demonstrated long-term kidney function preservation and achieved a clinically meaningful difference in eGFR total and chronic slope versus irbesartan, narrowly missing statistical significance in eGFR total slope while achieving statistical significance in eGFR chronic slope for purposes of regulatory review in the EU. Patients who completed the PROTECT double-blind portion of the study on treatment were eligible to participate in the open-label extension of the trial.
Focal segmental glomerulosclerosis (FSGS) is a rare proteinuric kidney disorder in both children and adults that is estimated to affect more than 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 kidney failure. 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. There is currently no approved pharmacologic indicated for the treatment of FSGS.
About the DUPLEX Study
The DUPLEX Study is the largest interventional study to date in FSGS. It is a global, randomized, multicenter, double-blind, parallel-arm, active-controlled Phase 3 clinical trial assessing the efficacy and safety of sparsentan in 371 patients ages 8 to 75 years with primary FSGS. After a two-week washout period, patients are randomized 1:1 to receive either sparsentan or irbesartan, the active control, and subsequently dose titrated to the maximum dose of 800 mg of sparsentan or 300 mg of irbesartan, as tolerated. In February 2021, the Company announced that the pivotal Phase 3 DUPLEX Study of sparsentan in FSGS achieved its pre-specified interim FSGS partial remission of proteinuria (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). The study’s primary efficacy endpoint in the U.S. is the eGFR total slope from day 1 to week 108 of treatment. The primary efficacy endpoint in Europe is the eGFR chronic slope, from week 6 to week 108 of treatment, following the initial acute effect of randomized treatment. In May 2023, the Company announced topline primary efficacy results from the DUPLEX Study of sparsentan in FSGS. The DUPLEX Study did not achieve the primary efficacy eGFR slope endpoint over 108 weeks of treatment. Secondary and topline exploratory endpoints trended favorably for sparsentan. Treatment with sparsentan resulted in a reduction of proteinuria that was sustained through 108 weeks of treatment. Results from the two-year analysis demonstrated that sparsentan was well-tolerated and has shown a comparable safety profile to irbesartan. Patients who completed the DUPLEX double-blind portion of the study on treatment were eligible to participate in the open-label extension of the trial.
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.
Vice President, Corporate Communications