ETA x AT1R

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

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 Sparsentan was well-tolerated with a consistent safety profile across all clinical trials conducted to date and comparable to irbesartan ST. GALLEN, Switzerland, May 2, 2023 /PRNewswire/ -- CSL Vifor today announced topline primary efficacy results from the pivotal Phase 3 DUPLEX Study of sparsentan, a Dual Endothelin Angiotensin Receptor Antagonist (DEARA), in focal segmental glomerulosclerosis (FSGS) from its partner Travere Therapeutics. At the end of the 108-week double-blind period, sparsentan was observed to have a 0.3 mL/min/1.73m2 per year (95% CI: -1.74, 2.41) favorable difference on eGFR total slope and a 0.9 mL/min/1.73m2 per year (95% CI: -1.27, 3.04) favorable difference on eGFR chronic slope compared to the active control irbesartan, which was not statistically significant. After 108 weeks of treatment, sparsentan achieved a mean reduction in proteinuria from baseline of 50%, compared to 32% for irbesartan. Results from the two-year analysis demonstrated that sparsentan was well-tolerated and has shown a comparable safety profile to irbesartan. "This is a preliminary data picture from the trial, and we will use additional time to analyze the full data set with our partner Travere," said Steve Pascoe, MD, Senior Vice President, Clinical and Therapeutic Area Strategy, CSL. "I would like to thank our partner, the patients and families, as well as the investigators and their staff members who participated and worked diligently to make this trial possible." In the DUPLEX Study, a total of 371 patients were randomized 1:1 to receive either sparsentan or irbesartan, the active control. eGFR Primary Efficacy Endpoints: Chronic slope (primary endpoint in Europe): From week 6 to week 108 of treatment, following the initial acute effect of randomized treatment, the difference in eGFR chronic slope was 0.9 mL/min/1.73m2 per year in favor of sparsentan (-4.8 mL/min per 1.73 m2 per year; 95% CI: -6.34, -3.27) versus the active control irbesartan (-5.7 mL/min per 1.73 m2 per year; 95% CI:-7.20, -4.18), p=0.4203. Total slope (primary endpoint in US) : From day one to week 108, the difference in eGFR total slope was 0.3 mL/min/1.73m2 per year in favor of sparsentan (-5.4 mL/min per 1.73 m2 per year; 95% CI: -6.89, -3.93) versus the active control irbesartan (-5.7 mL/min per 1.73 m2 per year; 95% CI: -7.20, -4.29), p=0.7491. The secondary, topline exploratory and hard endpoints in the study trended favorably for sparsentan. Proteinuria Two-Year Exploratory Endpoints: Urine protein-to-creatinine ratio ( UP/C): After 108 weeks of treatment, the change from baseline UP/C was 50% for sparsentan versus 32% for irbesartan. FSGS partial remission of proteinuria endpoint (FPRE): At week 108, 38% of patients on sparsentan achieved FPRE compared with 23% on irbesartan. Complete remission: 18% of patients on sparsentan versus 7% on irbesartan achieved complete remission of proteinuria (UP/C <0.3 g/g) at any time during the double-blind period. A preliminary review of the safety results through 108 weeks of treatment indicate sparsentan has been generally well-tolerated and the overall safety profile in the study to date has been generally consistent between treatment groups. Travere Therapeutics intends to complete a full evaluation of the data from the DUPLEX Study and work with study investigators on future presentations and publication of the results at an upcoming medical meeting and/or in a peer-reviewed publication. 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 US with similar prevalence in Europe. The disorder is defined by progressive scarring of the kidney and often leads to renal 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 therapy 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, Travere Therapeutics announced that the ongoing 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). 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. 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. The study's primary efficacy endpoint in the US is the eGFR total slope from day 1 to week 108 of treatment. Patients that completed the DUPLEX double-blind portion of the study on treatment were eligible to participate in the open-label portion of the trial. 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, protects podocytes, prevents glomerulosclerosis and mesangial cell proliferation, and reduces proteinuria. Sparsentan is also currently being evaluated in the pivotal phase-III PROTECT study for the treatment of IgA nephropathy (IgAN). In August 2021, Travere Therapeutics announced that the PROTECT Study met its pre-specified interim primary efficacy endpoint. After 36 weeks of treatment, patients receiving sparsentan achieved a mean reduction in proteinuria from baseline of 49.8 percent, compared to a mean reduction in proteinuria from baseline of 15.1 percent for irbesartan treated patients (p<0.0001). FDA has recently approved sparsentan under an accelerated approval procedure to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression. The PROTECT Study is fully enrolled and is scheduled to continue as planned on a blinded basis to assess the treatment effect on eGFR slope over 110 weeks in the confirmatory endpoint analysis. Topline results from the confirmatory endpoint analysis are expected in the second half of 2023. CSL Vifor and Travere Therapeutics signed a license agreement for CSL Vifor to commercialize Travere's lead product, sparsentan, in Europe, Australia and New Zealand in the following indications: focal segmental glomerulosclerosis (FSGS) and IgA Nephropathy (IgAN) – rare kidney disorders that often lead to end-stage kidney disease. CSL Vifor, together with its partner Travere Therapeutics, will determine next steps for sparsentan in FSGS in the licensed territory. CSL Vifor announced in August 2022 that the EMA had accepted for review a Conditional Marketing Authorization (CMA) application for sparsentan for the treatment of IgAN. The regulatory procedure is ongoing and a review decision on a potential approval is expected in the second half of 2023. 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, . SOURCE Vifor International AG (CSL Vifor)

Data support the Company’s lead investigational product candidate sparsentanSAN DIEGO, Oct. 26, 2022 (GLOBE NEWSWIRE) -- Travere Therapeutics, Inc. (NASDAQ: TVTX) today announced that the Company and its collaborators will present data from its sparsentan programs, including long-term clinical data from the ongoing Phase 2 DUET Study in focal segmental glomerulosclerosis (FSGS), as well as non-clinical data exploring the potential for sparsentan to protect kidney function at the American Society of Nephrology (ASN) Kidney Week 2022. The company will also present data on the role of proteinuria in IgA nephropathy (IgAN) and on the humanistic burden of IgAN on patients and caregivers. ASN Kidney Week 2022 is being held November 3-6, 2022, in Orlando, Florida. Oral Presentations Sparsentan Improves Glomerular Endothelial and Podocyte Functions and Augments Protective Tissue Repair in a Mouse Model of Focal Segmental Glomerulosclerosis (FSGS) Session: Glomerular Diseases: From Bench to BedsideOral Presentation: FR-OR56Location: Session Room: W414 (Orange County Convention Center, West Building)Date & Time: November 4, 2022, from 5:15 to 5:24 p.m. ET Long-Term Efficacy and Safety of Sparsentan in FSGS: 240-Week Analysis of the DUET Open-Label Extension (OLE)Session: Glomerular Diseases: From Bench to BedsideOral Presentation: FR-OR57 Location: W414 (Orange County Convention Center, West Building) Date & Time: November 4, from 5:24 to 5:33 p.m. ET Poster Presentations Evaluating the Predictors of Structural Features in Kidney Biopsies from Adults with Focal Segmental Glomerulosclerosis Poster #: TH-PO478Session: Glomerular Diseases: Clinical, Outcomes, Trials – IDate, Time & Location: November 3, 2022, from 10 a.m. to 12 p.m. ET, Hall E Proteinuria and Its Association With Disease Progression in IgA Nephropathy: Analysis of the UK National RaDaR IgA Nephropathy Cohort Poster #: TH-PO494 Session: Glomerular Diseases: Clinical, Outcomes, Trials - I Date, Time & Location: November 3, 2022, from 10 a.m. to 12 p.m. ET, Hall E Health State Utility Values for Immunoglobulin A Nephropathy (IgAN) Poster #: TH-PO496Session: Glomerular Diseases: Clinical, Outcomes, Trials – IDate, Time & Location: November 3, 2022, from 10 a.m. to 12 p.m. ET, Hall E Effect of Multiple Doses of Sparsentan on the Single-Dose Pharmacokinetics of Dapagliflozin: Open-Label Drug-Drug Interaction Study in Healthy Adults Poster #: FR-PO217 Session Title: Pharmacology Date, Time & Location: November 4, 10 a.m. to 12 p.m. ET, Hall E Predictors of Progression to Kidney Failure in Patients with Focal Segmental Glomerulosclerosis Poster #: FR-PO662Session: Glomerular Diseases: Clinical, Outcomes, Trials - II Date, Time & Location: November 4, 10 a.m. to 12 p.m. ET, Hall E Development of a Treatment Response Prediction Strategy for Sparsentan in Glomerular Disease Poster #: FR-PO724Session: Glomerular Diseases: Podocyte Biology – IDate, Time & Location: November 4, 10 a.m. to 12 p.m. ET, Hall E Differentiating Primary and Secondary FSGS Using Non-Invasive Urine Biomarkers Poster #: FR-PO913Session: CKD: Epidemiology, Risk Factors, Prevention – IIDate, Time & Location: November 4, 10 a.m. to 12 p.m. ET, Hall E Humanistic Burden of Patients with Immunoglobulin A Nephropathy (IgAN) in the United States (US): Preliminary Results from HONUS Study Poster Board #: SA-PO699Session: Glomerular Diseases: Clinical, Outcomes, Trials - III Date, Time & Location: November 5, 2022, from 10 a.m. to 12 p.m. ET, Hall E A Retrospective Analysis of Cardiovascular Disease (CVD) Events in Prevalent Patients with Focal Segmental Glomerulosclerosis (FSGS) in the USPoster #: SA-PO702 Session: Glomerular Diseases: Clinical, Outcomes, Trials - IIIDate, Time & Location: November 5, 2022, from 10 a.m. to 12 p.m. ET, Hall E 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<0.0001). Preliminary results from the interim analysis suggest that at the time of the interim assessment, sparsentan had been generally well tolerated and performed consistent with the observed safety profile to date. In the Phase 2 DUET Study of sparsentan in FSGS, the combined treatment group met its primary efficacy endpoint, demonstrating a greater than two-fold reduction in proteinuria compared to irbesartan, and was generally well tolerated after the eight-week, double-blind treatment period. Irbesartan is part of a class of drugs used to manage FSGS and IgAN in the absence of an approved pharmacologic treatment. An NDA for accelerated approval of sparsentan in IgAN is currently being evaluated by the FDA under Priority Review designation. If approved for both indications, sparsentan could potentially be the first medicine approved for both FSGS and IgAN. 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 "may", "might", "believes", "thinks", "anticipates", "plans", "expects", "intends" or similar expressions. In addition, expressions of our strategies, intentions or plans are also forward-looking statements. 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. Such forward-looking statements include, but are not limited to, references to the efficacy, safety and tolerability profile of sparsentan based on the preliminary data from the DUPLEX and PROTECT Studies’ interim analyses and the potential for sparsentan to be the first medicine approved for both FSGS and IgAN, if approved for both indications. 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, including the Subpart H accelerated approval pathway in the United States and the conditional marketing authorization (CMA) pathway in the European Union, as well as risks and uncertainties associated with the Company’s business and finances in general. Specifically, the Company faces the risk that the Phase 3 clinical trial of sparsentan in IgAN will not demonstrate that sparsentan is safe or effective or serve as a basis for accelerated approval of sparsentan as planned; risk that the Phase 3 clinical trial of sparsentan in FSGS will not demonstrate that sparsentan is safe or effective or serve as the basis for traditional approval of sparsentan as planned; and risk that sparsentan will not be approved for efficacy, safety, regulatory or other reasons, and for each of the programs, 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. Also, there is no guarantee that the non-clinical data that are summarized in the abstracts that are a subject of this press release will translate to a viable therapeutic approach in patients. The Company 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; risk 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; 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. 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 as included in the Company's most recent Form 10-K, Form 10-Q and other filings with the Securities and Exchange Commission. Contact: Investors:Investor Relations888-969-7879 [email protected]:Nivi NehraVice President, Corporate Communications888-969-7879