Travere Therapeutics to Submit sNDA for FILSPARI® (sparsentan) in FSGS
Travere Therapeutics (TVTX) has announced plans to submit a supplemental New Drug Application (sNDA) for FILSPARI to treat focal segmental glomerulosclerosis (FSGS), following a successful Type C meeting with the FDA. The submission, expected around the end of Q1 2025, will be based on data from Phase 3 DUPLEX and Phase 2 DUET studies.
If approved, FILSPARI could become the first approved medicine for FSGS, a rare kidney disorder affecting over 40,000 adults and children in the U.S. The submission is supported by recent findings from the PARASOL workgroup, which confirmed that reduction in proteinuria over 24 months is strongly associated with reduced risk of kidney failure in FSGS patients.
Travere Therapeutics (TVTX) ha annunciato piani per presentare una domanda supplementare di nuova autorizzazione (sNDA) per FILSPARI per il trattamento della glomerulosclerosi segmentaria focale (FSGS), dopo un incontro di tipo C fruttuoso con la FDA. La presentazione, prevista verso la fine del primo trimestre del 2025, si baserà su dati degli studi di Fase 3 DUPLEX e di Fase 2 DUET.
Se approvato, FILSPARI potrebbe diventare il primo farmaco approvato per la FSGS, un raro disturbo renale che colpisce più di 40.000 adulti e bambini negli Stati Uniti. La presentazione è supportata da recenti scoperte del gruppo di lavoro PARASOL, che ha confermato che la riduzione della proteinuria nel corso di 24 mesi è fortemente associata a un rischio ridotto di insufficienza renale nei pazienti con FSGS.
Travere Therapeutics (TVTX) ha anunciado planes para presentar una solicitud suplementaria de nuevo fármaco (sNDA) para FILSPARI para tratar la glomeruloesclerosis segmentaria focal (FSGS), tras haber mantenido una reunión exitosa tipo C con la FDA. Se espera que la presentación, programada para finales del primer trimestre de 2025, se base en datos de los estudios de Fase 3 DUPLEX y Fase 2 DUET.
Si se aprueba, FILSPARI podría convertirse en el primer medicamento aprobado para la FSGS, un raro trastorno renal que afecta a más de 40,000 adultos y niños en los EE. UU. La presentación cuenta con el apoyo de recientes hallazgos del grupo de trabajo PARASOL, que confirmaron que la reducción de proteinuria durante 24 meses está fuertemente asociada con un menor riesgo de insuficiencia renal en pacientes con FSGS.
Travere Therapeutics (TVTX)는 FDA와의 성공적인 유형 C 미팅 이후 FILSPARI를 중심으로 국소 세그먼트 사구체 경화증(FSGS)을 치료하기 위한 보충 신약 신청(sNDA)을 제출할 계획을 발표했습니다. 제출은 2025년 1분기 말경에 예상되며, 3상 DUPLEX 시험과 2상 DUET 시험의 데이터를 기반으로 할 것입니다.
승인될 경우, FILSPARI는 미국에서 40,000명 이상의 성인과 어린이에게 영향을 미치는 드문 신장 질환 FSGS를 위한 최초의 승인된 약물이 될 수 있습니다. 이번 제출은 PARASOL 작업 그룹의 최근 연구 결과를 뒷받침하고 있으며, 이 연구에서는 24개월 동안 단백뇨 감소가 FSGS 환자의 신장 장애 위험 감소와 강한 연관이 있음을 확인했습니다.
Travere Therapeutics (TVTX) a annoncé des plans pour soumettre une demande de nouveau médicament complémentaire (sNDA) pour FILSPARI afin de traiter la glomérulosclérose segmentaire focale (FSGS), suite à une réunion de type C réussie avec la FDA. La soumission, prévue pour la fin du premier trimestre 2025, sera basée sur les données des études de Phase 3 DUPLEX et de Phase 2 DUET.
Si elle est approuvée, FILSPARI pourrait devenir le premier médicament approuvé pour la FSGS, un trouble rare des reins touchant plus de 40 000 adultes et enfants aux États-Unis. La soumission est soutenue par des résultats récents du groupe de travail PARASOL, qui ont confirmé qu'une réduction de la protéinurie sur 24 mois est fortement associée à un risque réduit d'insuffisance rénale chez les patients atteints de FSGS.
Travere Therapeutics (TVTX) hat Pläne angekündigt, einen ergänzenden Antrag auf Zulassung eines neuen Arzneimittels (sNDA) für FILSPARI zur Behandlung der fokalen segmentalen Glomerulosklerose (FSGS) einzureichen, nachdem ein erfolgreiches Typ-C-Gespräch mit der FDA geführt wurde. Die Einreichung, die gegen Ende des ersten Quartals 2025 erwartet wird, basiert auf Daten aus der Phase-3-Studie DUPLEX und der Phase-2-Studie DUET.
Wenn genehmigt, könnte FILSPARI das erste zugelassene Medikament für FSGS werden, eine seltene Nierenerkrankung, die mehr als 40.000 Erwachsene und Kinder in den USA betrifft. Die Einreichung wird durch aktuelle Erkenntnisse der PARASOL-Arbeitsgruppe gestützt, die bestätigt hat, dass eine Reduzierung der Proteinurie über 24 Monate stark mit einem verringerten Risiko für Nierenversagen bei FSGS-Patienten assoziiert ist.
- Potential first-mover advantage in FSGS treatment market of 40,000+ patients
- FDA alignment on sNDA submission pathway achieved
- Strong clinical data support from both Phase 2 and Phase 3 studies
- PARASOL workgroup findings validate the company's clinical approach
- Lengthy timeline to potential approval with submission not until Q1 2025
- No guaranteed FDA approval despite positive meeting outcome
Insights
The planned sNDA submission for FILSPARI in FSGS represents a major catalyst for Travere Therapeutics, targeting an indication with no currently approved treatments affecting over 40,000 patients in the U.S. alone. The regulatory strategy appears robust, leveraging data from two of the largest FSGS clinical trials to date.
The PARASOL workgroup's validation of proteinuria reduction as a clinically meaningful endpoint significantly de-risks the regulatory pathway. This scientific validation is particularly important as it establishes a clear link between FILSPARI's demonstrated effect on proteinuria and meaningful clinical outcomes in kidney health.
The market opportunity is substantial, considering FSGS is a leading cause of kidney failure. With no approved treatments, FILSPARI could become the standard of care in this space. The timing of the submission around Q1 2025 suggests potential approval could come by early 2026, assuming standard FDA review timelines.
Importantly, this would represent FILSPARI's second indication, following its previous approval in IgA nephropathy. This expansion could significantly broaden the drug's commercial potential and strengthen Travere's position in rare kidney diseases. The dual-indication strategy could create substantial operational leverage in commercialization efforts, as the same sales infrastructure could serve both markets.
Company completed Type C meeting with FDA, aligning on its plan to submit an sNDA; submission expected around end of 1Q25
If approved, FILSPARI could be the first and only approved medicine indicated for FSGS, a rare kidney disorder and leading cause of kidney failure
sNDA submission to be based on results from Phase 3 DUPLEX and Phase 2 DUET studies of FILSPARI in FSGS
Company to host conference call and webcast today at 8:30 a.m. ET
SAN DIEGO, Feb. 11, 2025 (GLOBE NEWSWIRE) -- Travere Therapeutics, Inc. (Nasdaq: TVTX) today announced the Company has completed its Type C meeting with the U.S. Food and Drug Administration (FDA) and plans to submit a supplemental New Drug Application (sNDA) seeking traditional approval of FILSPARI for focal segmental glomerulosclerosis (FSGS). The sNDA will be based on existing data from the Phase 3 DUPLEX and Phase 2 DUET studies of FILSPARI and is expected to be submitted around the end of the first quarter of 2025.
“We are pleased with the outcome of our Type C meeting and to be moving forward with an sNDA submission to add a potential FSGS indication for FILSPARI in the U.S. Treatment options for FSGS are desperately needed as there are currently no approved medicines indicated for this devastating, progressive and complex rare kidney disorder that affects more than 40,000 adults and children in the U.S.,” said Eric Dube, Ph.D., president and chief executive officer of Travere Therapeutics. “The DUPLEX and DUET studies, two of the largest interventional studies conducted to-date in FSGS, will serve as the basis for our submission. Importantly, the results from these studies are in alignment with the recent findings of the PARASOL workgroup that support the importance of proteinuria in FSGS. We look forward to working with the FDA throughout the upcoming review process.”
The Type C meeting follows the recent public workshop led by the PARASOL (Proteinuria and GFR as Clinical Trial Endpoints in Focal Segmental Glomerulosclerosis [FSGS]) workgroup. The principal finding from PARASOL was that in FSGS, reduction in proteinuria over 24 months is strongly associated with a reduction in the risk of kidney failure, and responder definitions based on thresholds of proteinuria are both biologically plausible and strongly supported by epidemiological data.
Conference call information
Travere Therapeutics will host a conference call and webcast to discuss these updates today, Tuesday, February 11, 2025, at 8:30 a.m. ET. To participate in the conference call, dial +1 (800) 549-8228 (U.S.) or +1 (646) 564-2877 (International), conference ID 05607.
The webcast can be accessed on the Investor page of Travere’s website at ir.travere.com/events-presentations. Following a live webcast, archived version of the call will be available for 30 days on the Company’s website.
About FSGS
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 and DUET Studies
The Phase 3 DUPLEX Study is the largest interventional study to date in FSGS, and the only study in FSGS against a maximally dosed active comparator. While DUPLEX achieved its pre-specified interim FSGS partial remission of proteinuria (FPRE) endpoint with statistical significance at 36 weeks, it did not achieve the primary efficacy eGFR slope endpoint over 108 weeks of treatment. The two-year results from the study were published in the New England Journal of Medicine and showed that sparsentan delivered clinically meaningful benefit at 108 weeks with significant proteinuria reduction, higher rates of partial and complete remission, and a lower rate of end-stage kidney disease compared to the active control. The Phase 2 DUET Study of sparsentan in FSGS met the primary efficacy endpoint for the combined treatment group, demonstrating a greater than two-fold reduction in proteinuria compared to irbesartan. Sparsentan was well-tolerated with a safety profile that was consistent across all clinical trials conducted to date and comparable to the active control, irbesartan, including no drug-induced liver injury and no fluid overload. Patients who completed the DUPLEX and DUET double-blind portions of the studies on treatment were eligible to participate in the open-label extension of the trials.
About PARASOL
PARASOL is a collaborative academic and regulator-led international effort that aims to define the quantitative relationships between short-term changes in biomarkers (proteinuria and GFR) and long-term outcomes in order to support the use of alternative proteinuria-based endpoints as a basis for accelerated and traditional approval. The project is sponsored by FDA, NephCure, the International Society of Glomerular Disease, the Kidney Health Initiative, and the National Kidney Foundation. The data analysis is led by a team from the Michigan Kidney Translational Medicine Center at the University of Michigan.
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. For more information, visit travere.com
FILSPARI® (sparsentan) U.S. Indication
FILSPARI (sparsentan) is indicated to slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: HEPATOTOXICITY AND EMBRYO-FETAL TOXICITY
Because of the risks of hepatotoxicity and birth defects, FILSPARI is available only through a restricted program called the FILSPARI REMS. Under the FILSPARI REMS, prescribers, patients and pharmacies must enroll in the program.
Hepatotoxicity
Some Endothelin Receptor Antagonists (ERAs) have caused elevations of aminotransferases, hepatotoxicity, and liver failure. In clinical studies, elevations in aminotransferases (ALT or AST) of at least 3-times the Upper Limit of Normal (ULN) have been observed in up to
Measure transaminases and bilirubin before initiating treatment and monthly for the first 12 months, and then every 3 months during treatment. Interrupt treatment and closely monitor patients who develop aminotransferase elevations more than 3x ULN.
FILSPARI should generally be avoided in patients with elevated aminotransferases (>3x ULN) at baseline because monitoring for hepatotoxicity may be more difficult and these patients may be at increased risk for serious hepatotoxicity.
Embryo-Fetal Toxicity
FILSPARI can cause major birth defects if used by pregnant patients based on animal data. Therefore, pregnancy testing is required before the initiation of treatment, during treatment and one month after discontinuation of treatment with FILSPARI. Patients who can become pregnant must use effective contraception before the initiation of treatment, during treatment, and for one month after discontinuation of treatment with FILSPARI.
Contraindications
FILSPARI is contraindicated in patients who are pregnant. Do not coadminister FILSPARI with angiotensin receptor blockers (ARBs), ERAs, or aliskiren.
Warnings and Precautions
- Hepatotoxicity: Elevations in ALT or AST of at least 3-fold ULN have been observed in up to
3.5% of FILSPARI-treated patients, including cases confirmed with rechallenge. While no concurrent elevations in bilirubin >2-times ULN or cases of liver failure were observed in FILSPARI-treated patients, some ERAs have caused elevations of aminotransferases, hepatotoxicity, and liver failure. To reduce the risk of potential serious hepatotoxicity, measure serum aminotransferase levels and total bilirubin prior to initiation of treatment and monthly for the first 12 months, then every 3 months during treatment.
Advise patients with symptoms suggesting hepatotoxicity (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching) to immediately stop treatment with FILSPARI and seek medical attention. If aminotransferase levels are abnormal at any time during treatment, interrupt FILSPARI and monitor as recommended.
Consider re-initiation of FILSPARI only when hepatic enzyme levels and bilirubin return to pretreatment values and only in patients who have not experienced clinical symptoms of hepatotoxicity. Avoid initiation of FILSPARI in patients with elevated aminotransferases (>3x ULN) prior to drug initiation because monitoring hepatotoxicity in these patients may be more difficult and these patients may be at increased risk for serious hepatotoxicity.
- Embryo-Fetal Toxicity: FILSPARI can cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy. Advise patients who can become pregnant of the potential risk to a fetus. Obtain a pregnancy test prior to initiation of treatment with FILSPARI, monthly during treatment, and one month after discontinuation of treatment. Advise patients who can become pregnant to use effective contraception prior to initiation of treatment, during treatment, and for one month after discontinuation of treatment with FILSPARI.
- FILSPARI REMS: Due to the risk of hepatotoxicity and embryo-fetal toxicity, FILSPARI is available only through a restricted program called the FILSPARI REMS. Prescribers, patients, and pharmacies must be enrolled in the REMS program and comply with all requirements (www.filsparirems.com).
- Hypotension: Hypotension has been observed in patients treated with ARBs and ERAs. There was a greater incidence of hypotension-associated adverse events, some serious, including dizziness, in patients treated with FILSPARI compared to irbesartan. In patients at risk for hypotension, consider eliminating or adjusting other antihypertensive medications and maintaining appropriate volume status. If hypotension develops, despite elimination or reduction of other antihypertensive medications, consider a dose reduction or dose interruption of FILSPARI. A transient hypotensive response is not a contraindication to further dosing of FILSPARI, which can be given once blood pressure has stabilized.
- Acute Kidney Injury: Monitor kidney function periodically. Drugs that inhibit the renin-angiotensin system (RAS) can cause kidney injury. Patients whose kidney function may depend in part on the activity of the RAS (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute kidney injury on FILSPARI. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in kidney function while on FILSPARI.
- Hyperkalemia: Monitor serum potassium periodically and treat appropriately. Patients with advanced kidney disease, taking concomitant potassium-increasing drugs (e.g., potassium supplements, potassium-sparing diuretics), or using potassium-containing salt substitutes are at increased risk for developing hyperkalemia. Dosage reduction or discontinuation of FILSPARI may be required.
- Fluid Retention: Fluid retention may occur with ERAs, and has been observed in clinical studies with FILSPARI. FILSPARI has not been evaluated in patients with heart failure. If clinically significant fluid retention develops, evaluate the patient to determine the cause and the potential need to initiate or modify the dose of diuretic treatment then consider modifying the dose of FILSPARI.
Most common adverse reactions
The most common adverse reactions (≥
Drug interactions
- Renin-Angiotensin System (RAS) Inhibitors and ERAs: Do not coadminister FILSPARI with ARBs, ERAs, or aliskiren due to increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure).
- Strong and Moderate CYP3A Inhibitors: Avoid concomitant use of FILSPARI with strong CYP3A inhibitors. If a strong CYP3A inhibitor cannot be avoided, interrupt FILSPARI treatment. When resuming treatment with FILSPARI, consider dose titration. Monitor blood pressure, serum potassium, edema, and kidney function regularly when used concomitantly with moderate CYP3A inhibitors. Concomitant use with a strong CYP3A inhibitor increases sparsentan exposure which may increase the risk of FILSPARI adverse reactions.
- Strong CYP3A Inducers: Avoid concomitant use with a strong CYP3A inducer. Concomitant use with a strong CYP3A inducer decreases sparsentan exposure which may reduce FILSPARI efficacy.
- Antacids and Acid Reducing Agents: Administer FILSPARI 2 hours before or after administration of antacids. Avoid concomitant use of acid reducing agents (histamine H2 receptor antagonist and PPI proton pump inhibitor) with FILSPARI. Sparsentan exhibits pH-dependent solubility. Antacids or acid reducing agents may decrease sparsentan exposure which may reduce FILSPARI efficacy.
- Non-Steroidal Anti-Inflammatory Agents (NSAIDs), Including Selective Cyclooxygenase-2 (COX-2) Inhibitors: Monitor for signs of worsening renal function with concomitant use with NSAIDs (including selective COX-2 inhibitors). In patients with volume depletion (including those on diuretic therapy) or with impaired kidney function, concomitant use of NSAIDs (including selective COX-2 inhibitors) with drugs that antagonize the angiotensin II receptor may result in deterioration of kidney function, including possible kidney failure.
- CYP2B6, 2C9, and 2C19 Substrates: Monitor for efficacy of concurrently administered CYP2B6, 2C9, and 2C19 substrates and consider dosage adjustment in accordance with the Prescribing Information. Sparsentan decreases exposure of these substrates, which may reduce efficacy related to these substrates.
- P-gp and BCRP Substrates: Avoid concomitant use of sensitive substrates of P-gp and BCRP with FILSPARI. Sparsentan may increase exposure of these transporter substrates, which may increase the risk of adverse reactions related to these substrates.
- Agents Increasing Serum Potassium: Monitor serum potassium frequently in patients treated with FILSPARI and other agents that increase serum potassium. Concomitant use of FILSPARI with potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other drugs that raise serum potassium levels may result in hyperkalemia.
Please see the full Prescribing Information, including BOXED WARNING, for additional Important Safety Information.
Forward Looking Statements
This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, these statements are often identified by the words “on-track,” “positioned,” “look forward to,” “will,” “would,” “may,” “might,” “believes,” “anticipates,” “plans,” “expects,” “intends,” “potential,” or similar expressions. In addition, expressions of strategies, intentions or plans are also forward-looking statements. Such forward-looking statements include, but are not limited to, references to: plans and expectations regarding the submission of an sNDA for FILSPARI in FSGS, and expectations regarding the timing and outcome thereof; statements regarding the potential for FILSPARI to be the first and only approved medicine indicated for FSGS; references to the estimated size of the patient population; references to the potential impact that the PARASOL group’s findings could have on the review of the sNDA, and interpretations of the results from DUPLEX and DUET in the context of PARASOL’s findings; and statements regarding working with FDA throughout the upcoming review process. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are risks and uncertainties related to the Company’s planned submission of an sNDA for FILSPARI in FSGS, including the timing and outcome thereof. There is no guarantee that the FDA will accept the sNDA for filing, will grant priority review of the sNDA or grant approval of FILSPARI for FSGS. The Company also faces risks related to its business and finances in general, the success of its commercial products, risks and uncertainties associated with its preclinical and clinical stage pipeline, risks and uncertainties associated with the regulatory review and approval process, risks and uncertainties associated with enrollment of clinical trials for rare diseases, and risks that ongoing or planned clinical trials may not succeed or may be delayed for safety, regulatory or other reasons. Specifically, the Company faces risks associated with the ongoing commercial launch of FILSPARI in IgAN, the timing and potential outcome of its and its partners’ clinical studies, market acceptance of its commercial products including efficacy, safety, price, reimbursement, and benefit over competing therapies, risks related to the challenges of manufacturing scale-up, risks associated with the successful development and execution of commercial strategies for such products, including FILSPARI, and risks and uncertainties related to the new administration and matters related to the funding and staffing of government agencies including the FDA. The Company also faces the risk that it will be unable to raise additional funding that may be required to complete development of any or all of its product candidates, including as a result of macroeconomic conditions; risks relating to the Company’s dependence on contractors for clinical drug supply and commercial manufacturing; uncertainties relating to patent protection and exclusivity periods and intellectual property rights of third parties; risks associated with regulatory interactions; and risks and uncertainties relating to competitive products, including current and potential future generic competition with certain of the Company’s products, and technological changes that may limit demand for the Company’s products. The Company also faces additional risks associated with global and macroeconomic conditions, including health epidemics and pandemics, including risks related to potential disruptions to clinical trials, commercialization activity, supply chain, and manufacturing operations. You are cautioned not to place undue reliance on these forward-looking statements as there are important factors that could cause actual results to differ materially from those in forward-looking statements, many of which are beyond our control. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Investors are referred to the full discussion of risks and uncertainties, including under the heading “Risk Factors”, as included in the Company’s most recent Form 10-K, Form 10-Q and other filings with the Securities and Exchange Commission.
Contact Info
| Media: 888-969-7879 mediarelations@travere.com | Investors: 888-969-7879 IR@travere.com |
FAQ
When will Travere Therapeutics (TVTX) submit the sNDA for FILSPARI's FSGS indication?
What is the potential market size for FILSPARI in FSGS treatment?
What clinical studies support TVTX's sNDA submission for FILSPARI?
What were the key findings from the PARASOL workgroup supporting FILSPARI's development?
Would FILSPARI be the first FDA-approved treatment for FSGS if approved?
