Data presentations highlight the results for FILSPARI®(sparsentan), the only approved kidney-targeted medicine for IgA nephropathy, when used as a first-line treatment, and in combination with other therapies
Late-breaking presentation details outcomes of sparsentan’s effect in a subgroup of high-risk patients with genetic focal segmental glomerulosclerosis
SAN DIEGO, Oct. 14, 2024 (GLOBE NEWSWIRE) — Travere Therapeutics, Inc., (Nasdaq: TVTX) today announced that the Company will present 11 abstracts, including one late-breaking abstract at the upcoming American Society of Nephrology (ASN) Kidney Week 2024 in San Diego, CA, October 23-27, 2024.
Presentations will include new data from the SPARTAN Study highlighting efficacy and safety results of FILSPARI (sparsentan) in IgA nephropathy (IgAN) when used as a first-line treatment in newly diagnosed IgAN patients, an analysis from the PROTECT Study examining the clinical benefit of FILSPARI in IgAN regardless of participants’ baseline proteinuria, as well as patient-reported outcomes from the PROTECT and DUPLEX Studies. The Company will also present new data from the SPARTACUS Study, PROTECT open label extension, and real-world clinical experience of FILSPARI in IgAN demonstrating improvements in proteinuria reduction along with safety and efficacy data of sparsentan when used in combination with SGLT2 inhibitors. The late-breaking presentation is a post hoc analysis of outcomes of participants with genetic focal segmental glomerulosclerosis (gFSGS) from the DUPLEX Study.
“We look forward to presenting data from a growing body of evidence supportive of the clinical benefit in IgAN that FILSPARI can provide when used as a first-line treatment and in combination with other therapies,” said Jula Inrig, M.D., chief medical officer of Travere Therapeutics. “We’re also looking forward to presenting additional subgroup analyses from sparsentan in FSGS, where we will present data from a small group of high-risk patients with genetic FSGS, one of the most resistant to treatment.”
You can find more information on Travere’s presence at ASN here.
Late-Breaking Presentation
Outcomes of the DUPLEX Trial in Patients with Genetic Focal Segmental Glomerulosclerosis (gFSGS)
Poster: TH-PO1199
Session: Late-Breaking Science Posters
Exhibit Hall; October 24, 2024, from 10:00 a.m. to 12:00 p.m. PT
Oral Presentations
PROTECT Subgroup Analysis: Sparsentan Provides Clinical Benefits vs. Irbesartan in Patients with IgA Nephropathy (IgAN) with Proteinuria Above and Below 1 g/g
Oral: FR-OR57
Oral Abstract Session: IgA Nephropathy: New Therapies and Insights
Room 6D; October 25, 2024, 4:50–5:00 p.m. PT
Sparsentan as a First-Line Treatment of Incident Patients with IgA Nephropathy (IgAN): Interim Analysis of the SPARTAN Trial
Oral: FR-OR63
Oral Abstract Session: IgA Nephropathy: New Therapies and Insights
Room 6D; October 25, 2024, 5:40–5:50 p.m. PT
Poster Presentations
Sparsentan in Pediatric Patients with Rare Proteinuric Kidney Disease: Preliminary Findings from the EPPIK Study
Poster: TH-PO605
Poster Session: Membranous Nephropathy, FSGS, and Minimal Change Disease
Exhibit Hall; October 24, 2024, 10:00 a.m.–12:00 p.m. PT
Patient-Reported Outcomes in Adult Patients with Focal Segmental Glomerulosclerosis (FSGS): Sparsentan versus Irbesartan
Poster: TH-PO607
Poster Session: Membranous Nephropathy, FSGS, and Minimal Change Disease
Exhibit Hall; October 24, 2024, 10:00 a.m.–12:00 p.m. PT
Concomitant Sparsentan and Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2is) in Adults with IgA Nephropathy (SPARTACUS)
Poster: FR-PO849
Poster Session: IgA Nephropathy: Clinical, Outcomes, and Therapeutics
Exhibit Hall; October 25, 2024, 10:00 a.m.–12:00 p.m. PT
Concomitant Sparsentan and Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2is) in Patients with IgA Nephropathy (IgAN) in the PROTECT Open-Label Extension (OLE)
Poster: FR-PO851
Poster Session: IgA Nephropathy: Clinical, Outcomes, and Therapeutics
Exhibit Hall; October 25, 2024, 10:00 a.m.–12:00 p.m. PT
Patient-Reported Outcomes in the PROTECT Clinical Trial Comparing Sparsentan with Irbesartan for Immunoglobulin A Nephropathy
Poster: FR-PO868
Poster Session: IgA Nephropathy: Clinical, Outcomes, and Therapeutics
Exhibit Hall; October 25, 2024, 10:00 a.m.–12:00 p.m. PT
Implications of Proteinuria Remission on Estimated Glomerular Filtration Rare (eGFR) Trajectory in Patients with IgA Nephropathy (IgAN) in PROTECT
Poster: FR-PO872
Poster Session: IgA Nephropathy: Clinical, Outcomes, and Therapeutics
Exhibit Hall; October 25, 2024, 10:00 a.m.–12:00 p.m. PT
Sparsentan in Combination with a Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) and Steroid as First-Line Treatment for IgA Nephropathy (IgAN): A Case Report
Poster: FR-PO906
Poster Session: IgA Nephropathy: Clinical, Outcomes, and Therapeutics
Exhibit Hall; October 25, 2024, 10:00 a.m.–12:00 p.m. PT
Sparsentan in Patients with Prior or Concurrent Immunosuppressive Treatment (IST) for IgA Nephropathy (IgAN): A Case Series
Poster: FR-PO907
Poster Session: IgA Nephropathy: Clinical, Outcomes, and Therapeutics
Exhibit Hall; October 25, 2024, 10:00 a.m.–12:00 p.m. PT
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 Focal Segmental Glomerulosclerosis
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. Sparsentan is not approved for use in FSGS. There is currently no approved pharmacologic indicated for the treatment of FSGS.
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 3.5% of FILSPARI-treated patients, including cases confirmed with rechallenge.
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 (≥5%) are hyperkalemia, hypotension (including orthostatic hypotension), peripheral edema, dizziness, anemia, and acute kidney injury.
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: the potential for FILSPARI to be used as a first-line treatment for IgAN, and in combination with other therapies; and statements relating to clinical studies, including but not limited to trial design, anticipated results and timing related thereto. 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 related to the timing and outcome of the studies described herein and uncertainties associated with the regulatory review and approval process, as well as 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. The Company also faces risks related to its business and finances in general, the success of its commercial products and risks and uncertainties associated with its preclinical and clinical stage pipeline. Specifically, the Company faces risks associated with the ongoing commercial launch of FILSPARI, market acceptance of its commercial products including efficacy, safety, price, reimbursement, and benefit over competing therapies, as well as risks associated with the successful development and execution of commercial strategies for such products, including FILSPARI. The risks and uncertainties the Company faces with respect to its preclinical and clinical stage pipeline include risk that the Company’s clinical candidates will not be found to be safe or effective and that current or anticipated future clinical trials will not proceed as planned. There is no guarantee that regulators will grant approval of sparsentan for FSGS. 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 |
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