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Committee for Medicinal Products for Human Use (CHMP) recommends approval of the conditional marketing authorization (CMA) for sparsentan for the treatment of IgA nephropathy (IgAN) in Europe Positive CHMP opinion is based on pivotal phase-III PROTECT study results European Commission decision is expected in Q2 2024 ST. GALLEN, Switzerland, Feb. 23, 2024 /PRNewswire/ -- CSL Vifor and Travere Therapeutics, Inc., (NASDAQ: TVTX) today announced that the European Medicines Agency's (EMA) CHMP has recommended approval of sparsentan for the treatment of adults with primary IgAN with a urine protein excretion >1.0 g/day (or urine protein-to-creatinine ratio ≥0.75 g/g). IgAN is a rare kidney disorder and a leading cause of kidney failure. The CHMP opinion provides the basis for the European Commission's final decision regarding CMA for sparsentan. If approved in Europe, sparsentan will be the first non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist for the treatment of IgAN. "The positive CHMP opinion for sparsentan is one step closer to bringing this treatment option to patients in Europe with IgAN, a rare and serious condition that can cause kidney disease," said Emmanuelle Lecomte Brisset, Senior Vice President and Head of Global Regulatory Affairs at CSL. "We look forward to the European Commission decision and to continuing to advance CSL's promise to provide innovative treatments for patients with kidney disease." "The positive recommendation from the CHMP represents a significant advancement towards the delivery of new treatment options for people living with IgAN, who face the risk of progression to kidney failure and who currently have no approved non-immunosuppressive treatment options. The PROTECT Study is the only head-to-head study in IgAN against a maximally labeled dose of irbesartan, a current standard of care. The study demonstrated treatment with sparsentan resulted in a rapid and sustained reduction in proteinuria and has the potential to preserve kidney function and significantly delay time to kidney failure compared to an active comparator, suggesting long-term benefits in IgAN," said Eric Dube, Ph.D., president and chief executive officer of Travere Therapeutics. "Together with CSL Vifor, we look forward to the European Commission's decision in the second quarter of 2024." The positive CHMP opinion is based on results from the pivotal phase-III PROTECT study of sparsentan in IgAN, In August 2022, CSL Vifor and Travere Therapeutics announced they had submitted a Marketing Authorization Application (MAA) for CMA to the EMA. The European Commission previously granted Orphan Medicinal Product Designation to sparsentan for the treatment of IgAN. If approved, sparsentan would receive a CMA in all member states of the European Union, as well as in Iceland, Liechtenstein and Norway. Sparsentan is currently marketed in the U.S. and granted accelerated approval by the U.S. Food and Drug Administration under the brand name FILSPARI® based on reduction in proteinuria. In 2021, Travere Therapeutics granted CSL Vifor exclusive commercialization rights for sparsentan in Europe, Australia and New Zealand. About CSL Vifor CSL Vifor is a global partner of choice for pharmaceuticals and innovative, leading therapies in iron deficiency and nephrology. We specialize in strategic global partnering, in-licensing and developing, manufacturing and marketing pharmaceutical products for precision healthcare, aiming to help patients around the world lead better, healthier lives. Headquartered in St. Gallen, Switzerland, CSL Vifor also includes the joint company Vifor Fresenius Medical Care Renal Pharma (with Fresenius Medical Care). The parent company, CSL (ASX: CSL; USOTC: CSLLY), headquartered in Melbourne, Australia, employs 32,000 people and delivers its lifesaving therapies to people in more than 100 countries. For more information about CSL Vifor visit, . 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. About IgA Nephropathy (IgAN) 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 glomerular disease worldwide and a leading cause of kidney failure. IgAN is estimated to affect up to 250,000 people in the licensed territories. 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 maximum tolerated dose and at least ­50% of maximum labelled dose of ACE or ARB therapy. About sparsentan Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist with high selectivity for 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, protects podocytes, prevents glomerulosclerosis and mesangial cell proliferation, and reduces proteinuria. Sparsentan is currently available in the US and was granted accelerated approval by the US Food and Drug Administration in February 2023 under the brand name FILSPARI® based on reduction in proteinuria. In September 2023, Travere Therapeutics reported two-year confirmatory results from the Phase 3 PROTECT Study of FILSPARI in IgAN. View original content to download multimedia: SOURCE Vifor International AG (CSL Vifor) Company Codes: NASDAQ-NMS:TVTX

SAN DIEGO, Sept. 26, 2023 (GLOBE NEWSWIRE) -- Travere Therapeutics, Inc. (NASDAQ: TVTX) today announced that the Company and its collaborators will present preliminary findings from the SPARTAN Study evaluating the potential effect of FILSPARI® (sparsentan) as a first-line therapy in patients with newly diagnosed IgA nephropathy (IgAN) in a late-breaking trial session at the 17th International Symposium on IgA Nephropathy (IIGANN2023) in Ryogoku, Tokyo, September 28-30, 2023. The Company will also present preclinical data supporting the nephroprotective mechanism of action of sparsentan, a dual endothelin angiotensin receptor antagonist, and an analysis of the UK National Registry of Rare Renal Diseases (RaDaR) which demonstrated that patients with IgAN traditionally considered ‘low-risk’, with proteinuria less than one gram per day, had high rates of kidney failure. “Patients with IgA nephropathy need both early and effective treatment options capable of significant and sustained reduction of proteinuria to preserve kidney function,” said Jula Inrig, M.D., chief medical officer of Travere Therapeutics. “We’re pleased to be presenting 24-week data on proteinuria reduction, blood pressure control, and safety from the ongoing SPARTAN Study evaluating the effect of sparsentan as a first-line treatment option in patients with newly diagnosed IgAN.” Sparsentan Treatment of Incident Patients With IgA Nephropathy as First-line Therapy: Interim Findings From the SPARTAN Trial Oral Session 7, Clinical Trial 2 Saturday, September 30, 10:55-11:55 a.m. JST, 3F KFC HallPresentation: LB1 Dual Blockade of Endothelin A and Angiotensin II Type 1 Receptors with Sparsentan is Protective in the gddY Mouse Model of IgA Nephropathy to a Greater Extent Than Losartan Poster 13; Session: Pathogenesis 2 September 29, 11:20 a.m. – 12:35 p.m. JST; 10F 10A KFC Hall Proteinuria and Disease Progression in the RaDaR IgAN Cohort Poster 49; Session: Diagnosis or Prediction September 29, 11:20 a.m. – 12:35 p.m. JST; 10F 10A KFC Hall 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 US and is one of the most common glomerular diseases in Europe and Japan. FILSPARI® (sparsentan) US Indication FILSPARI is an endothelin and angiotensin II receptor antagonist indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a UPCR ≥1.5 g/g. This indication is granted under accelerated approval based on reduction in proteinuria. It has not been established whether FILSPARI slows kidney function decline in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial. FILSPARI® (sparsentan) Important Safety Information BOXED WARNING: HEPATOTOXICITY AND EMBRYO-FETAL TOXICITYBecause 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. HepatotoxicitySome 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 2.5% 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 ToxicityFILSPARI 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. To reduce the risk of potential serious hepatotoxicity, measure serum aminotransferase levels and total bilirubin prior to initiation of treatment, 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. Embryo-Fetal Toxicity: FILSPARI can cause fetal harm. Advise patients who can become pregnant of the potential risk to a fetus. Obtain a pregnancy test and advise patients who can become pregnant to use effective contraception prior to, during, and one month after discontinuation of FILSPARI treatment. FILSPARI REMS: FILSPARI is available only through a restricted program under a REMS called the FILSPARI REMS. Important requirements include:— Prescribers must be certified with the FILSPARI REMS by enrolling and completing training.— All patients must enroll in the FILSPARI REMS prior to initiating treatment and comply with monitoring requirements.— Pharmacies that dispense FILSPARI must be certified with the FILSPARI REMS and must dispense only to patients who are authorized to receive FILSPARI. Further information is available at www.filsparirems.com or 1-833-513-1325. Hypotension: 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, consider a dose reduction or dose interruption of FILSPARI. Acute Kidney Injury: Monitor kidney function periodically. Patients whose kidney function may depend in part on the activity of the renin-angiotensin system (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 with FILSPARI. If clinically significant fluid retention develops, after evaluation, consider modifying the dose of FILSPARI. Most common adverse reactions (5%) with FILSPARI are peripheral edema, hypotension (including orthostatic hypotension), dizziness, hyperkalemia, and anemia. Drug interactions Renin-Angiotensin System (RAS) Inhibitors and ERAs: Do not coadminister FILSPARI with angiotensin receptor blockers (ARBs), ERAs, or aliskiren.Strong and Moderate CYP3A Inhibitors: Avoid concomitant use of FILSPARI with strong CYP3A inhibitors. Monitor blood pressure, serum potassium, edema, and kidney function regularly when used concomitantly with moderate CYP3A inhibitors.Strong CYP3A Inducers: Avoid concomitant use with a strong CYP3A inducer.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.Non-Steroidal Anti-Inflammatory Agents (NSAIDs), Including Selective Cyclooxygenase-2 (COX-2) Inhibitors: Monitor for signs of worsening renal function.CYP2B6, 2C9, and 2C19 Substrates: Monitor for efficacy of the concurrently administered CYP2B6, 2C9, and 2C19 substrates and consider dosage adjustment in accordance with the Prescribing Information.P-gp and BCRP Substrates: Avoid concomitant use of sensitive substrates of P-gp and BCRP with FILSPARI.Agents Increasing Serum Potassium: Monitor serum potassium frequently. 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. Use in specific populations Pregnancy / Females and Males of Reproductive Potential: FILSPARI can cause fetal harm, including birth defects and fetal death, when administered to a pregnant patient and is contraindicated during pregnancy. Pregnancy Testing / Contraception: Verify the pregnancy status and effective method of contraception prior to, during, and one month after discontinuation of FILSPARI treatment. The patient should contact their physician immediately for pregnancy testing if onset of menses is delayed or pregnancy is suspected. Lactation: Advise patients not to breastfeed during treatment with FILSPARI.Hepatic Impairment: Avoid use of FILSPARI in patients with any hepatic impairment (Child-Pugh class A-C). Please see Full Prescribing Information for FILSPARI here. 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 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 “anticipate,” “believe,” “expect,” “intend,” “may,” “might,” “objective,” “plan,” “will” or similar expressions. In addition, expressions of our strategies, intentions or plans are also forward-looking statements. Such forward-looking statements include, but are not limited to, references to the potential effect of FILSPARI® (sparsentan) as a first-line therapy in patients with newly diagnosed IgA nephropathy, references to data supporting the nephroprotective mechanism of action of sparsentan, and references to the SPARTAN Study. 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 associated with the regulatory review and approval process, risk associated with enrollment of clinical trials for rare diseases and risk that ongoing or planned clinical trials may not succeed or may be delayed for safety, regulatory or other reasons. The Company faces risks related to the commercial launch of a new product; risks associated with market acceptance of FILSPARI and its other products, including efficacy, safety, price, reimbursement and benefit over competing therapies; the risk that the results of the Phase 3 PROTECT Study of sparsentan in IgAN will not be deemed sufficient by the FDA to serve as the basis for an sNDA submission for traditional approval of sparsentan. There is no guarantee that the FDA will grant full approval of sparsentan for IgAN. The Company also faces 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. Media:Investors:Nivi NehraNaomi EichenbaumVice President, Corporate CommunicationsVice President, Investor Relations888-969-7879888-969-7879mediarelations@travere.comIR@travere.com

Scientists have uncovered new molecular targets on a cell receptor that play a major role in cardiovascular regulation. The findings could lead to improved drugs for heart disease, an unfortunate side effect of some cancer therapies. Scientists at City of Hope, one of the largest cancer research and treatment organizations in the United States and a leading research center for diabetes and other life-threatening illnesses, have uncovered new molecular targets on a cell receptor that play a major role in cardiovascular regulation. The findings could lead to improved drugs for heart disease, an unfortunate side effect of some cancer therapies. Science Signaling published the study this week. The City of Hope researchers led by Nagarajan Vaidehi, Ph.D., professor and chair of the Department of Computational and Quantitative Medicine within Beckman Research Institute of City of Hope, collaborating with a team at McGill University led by Stephane Laporte, Ph.D., revealed mechanisms on a receptor called Angiotensin II type 1, or AT1R, that allow hormones and drugs to transfer information on the cell surface. Unraveling these communication pathways enable scientists to take the next step in designing targeted therapies for cardiovascular disease. The study used a combination of computational methods and experiments to identify newer drug binding sites in the receptor AT1R that significantly expands the scope of potential targets for drug development, particularly new therapeutics that influence the activity of the receptor in heart disease. "We identified previously unknown domains and mechanisms within AT1R that enable the receptor to bind with molecules and transmit specific signals. Our work strongly suggests these regions offer promising targets for new treatments for cardiovascular diseases," Vaidehi said. "Equally exciting, is the finding that multiple drug binding sites exist on these proteins that bind to AT1R, paving the way for us to develop a new class of medicines with less side effects for patients." Current medicines act on the AT1R receptor to elicit specific cellular responses, but, until now, scientists have not decoded the mechanisms behind them. In this study, the team blended computational modeling with leading-edge approaches in structural biology and pharmacology to detect signaling within AT1R that dictates the receptor's responses to key intracellular pathways. Understanding the nuances behind this interaction will lay the foundation for researchers to design effective targeted therapies for cardiovascular diseases. Grants from the National Institutes of Health (R01-GM117923) and the Canadian Institutes of Health Research (PJT-162368 and PJT-173504) supported the research.