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Calliditas Therapeutics made the announcement today (August 18) that the FDA has accepted the submission for the supplemental New Drug Application (sNDA) for Tarpeyo – budesonide – delayed release capsules. Tarpeyo is currently approved under accelerated approval to reduce proteinuria in adults with primary Immunoglobulin A Nephropathy (IgAN) at risk of rapid disease progression. The Prescription Drug User Fee Act (PDUFA) goal date is December 20 this year (2023). Slow kidney decline Renee Aguiar-Lucander, CEO of Calliditas, said: “We are delighted to have been granted priority review by the FDA, which brings us one step closer to hopefully being able to provide Tarpeyo to all patients at risk of progression and provide physicians with a tool to target the source of this disease to slow kidney function decline. “The significant eGFR treatment benefit observed across the entire study population provides further evidence that Tarpeyo can be disease-modifying, potentially significantly delaying the need for dialysis or kidney transplantation for patients at risk.” The sNDA is based on the full data set from the phase 3 NefIgArd clinical trial, a randomized, double-blind, multicenter study evaluating the efficacy and safety of the drug (developed under the project name Nefecon) at a once-daily dose of 16 mg, compared to placebo, in adult patients with primary IgAN on optimized Renin-angiotensin system inhibitors (RASi) RASi therapy. RASi inhibitors, specifically angiotensin converting enzyme inhibitor or angiotensin 2 receptor blockers decrease proteinuria and slow the progressive loss of kidney function. googletag.cmd.push(function () { googletag.display('text-ad1'); }); Significant benefit of Nefecon Calliditas said the trial showed a statistically significant benefit of Nefecon over placebo in estimated glomerular filtration rate (eGFR) over the two-year study period made up of nine months treatment with Nefecon or placebo. This was followed by a 15-month follow-up period off the study drug. The data reflected treatment benefits across the entire study population regardless of UPCR baseline and showed a difference between Tarpeyo and placebo in two-year sGFR total slope of approximately 3mL/min per year using a robust regression method of analysis. “We take great pride in the strong clinical evidence we have gathered, which we believe demonstrates Tarpeyo's durable and clinically meaningful impact on kidney function in the treatment of IgAN,” said Richard Phillipson, Chief Medical Officer at Calliditas. “The combination of the significant eGFR benefit and the reduction in proteinuria lasting for the entire 15-month follow-up period in the full results of our phase 3 study provide strong rationale for establishing Tarpeyo as the standard of care for IgAN patients.” Calliditas is also collaborating with its European commercial partner, STADA Arzneimettel AG, to seek full approval of Nefecon (which received conditional approval under the brand name Kinpeygo) by the European Commission in the full study population.

FRIDAY, June 30, 2023 -- Globally, one in four heart failure patients die within the first year of their first heart failure-related hospitalization, according to a study published online June 21 in JACC: Heart Failure . Biykem Bozkurt, M.D., Ph.D., from Baylor College of Medicine in Houston, and colleagues described rehospitalizations, hospitalization costs, use of guideline-directed medical therapy, and mortality after hospitalization for heart failure. Analysis included electronic health record or claims data for 263,525 adult patients in Japan, Sweden, the United Kingdom, and the United States with a first heart failure discharge between 2018 and 2022. The researchers found that 28 percent of patients died within the first year posthospitalization heart failure (event rate: 28.4). Heart failure (event rate: 13.6) and chronic kidney disease (CKD; event rate: 4.5) drove rehospitalizations. Similarly, heart failure and CKD drove health care costs. There was little change seen between 2020 and 2022 for use of renin-angiotensin system inhibitors, sacubitril/valsartan, beta-blockers, and mineralocorticoid receptor antagonists. However, uptake of sodium-glucose cotransporter-2 inhibitors increased two- to sevenfold. "Incident posthospitalization heart failure rehospitalization risks and costs were high, and guideline-directed medical therapy use changed little in the year following discharge, highlighting the need to consider earlier and greater implementation of guideline-directed medical therapy to manage risks and reduce costs," the authors write. Several authors disclosed ties to the pharmaceutical industry. Medical writing support was provided by AstraZeneca, which also funds EVOLUTION HF, the longitudinal cohort study from where the data was pulled. Abstract/Full Text Posted June 2023

SAN DIEGO, June 08, 2023 (GLOBE NEWSWIRE) -- Travere Therapeutics Inc. (NASDAQ: TVTX) today announced that the Company and its collaborators will present nine abstracts, including the interim analysis from the ongoing Phase 3 PROTECT Study evaluating FILSPARI™ (sparsentan) versus an active comparator in IgA nephropathy (IgAN), at the 60th ERA Congress in Milan, Italy, June 15-18, 2023. Also included in the presentations is a new analysis of the UK RaDaR Registry estimating the delay in time to kidney failure or death based on proteinuria reduction in IgAN, which has been designated among the 10 best-ranked abstracts of 2023 by ERA. “We’re pleased to bring to the ERA Congress the strong interim results from our ongoing PROTECT Study which demonstrate that sparsentan significantly reduces proteinuria in IgA nephropathy,” said Jula Inrig, M.D., chief medical officer of Travere Therapeutics. “We also look forward to sharing more data from the IgA nephropathy field showing the relationship between reducing proteinuria in IgA nephropathy and preservation of kidney function.” Mini-Lecture Presentations Estimating Delay in Time to Kidney Failure or Death for Treatment Effects on Proteinuria in IgA Nephropathy Session: The Art of Staring at Urine: Studies in IgA Nephropathy Location & Time: Brown 1 & 2; Friday, June 16, 2023, 12:34 – 12:47 p.m. CEST *Among the 10 best-ranked abstracts of ERA Congress 2023 Superior Proteinuria Reduction with Sparsentan in Immunoglobulin A Nephropathy (IgAN): PROTECT Study Interim Analysis Session: The Art of Staring at Urine: Studies in IgA Nephropathy Location & Time: Brown 1 & 2, Friday, June 16, 2023, 1 - 1:15 p.m. CEST Modeling Long-term Outcomes for Patients with Immunoglobulin A Nephropathy (IgAN) from Short-term Proteinuria Data Session: Navigating the IgA Nephropathy Pathway Location & Time: Amber 1 & 2, Saturday, June 17, 2023, 3:45 - 4:00 p.m. CEST Alport Syndrome Natural History from the RaDaR Registry: Associations with Gene, Variant Type and Sex Session: Small Patients, Big Data Location & Time: Brown 1 & 2; Friday, June 16, 2023, 5:34 - 5:47 p.m. CEST Moderated Oral Presentation Outcomes in SRNS (FSGS) Patients in the UK RaDaR Idiopathic Nephrotic Syndrome Registry and Their Relationship with Time-Averaged Proteinuria Session: Moderated Orals 2.3 Location & Time: Amber 6; Saturday, June 17, 2023, 2:57 - 3:02 p.m. CEST Focused Oral Presentations Matching-Adjusted Indirect Comparison of Sparsentan Versus Delayed-Release Formulation Budesonide for Proteinuria Reduction in Adult Patients with IgA Nephropathy Session: Glomerular & Tubulo-interstitial Diseases Location & Time: Room 9; Friday, June 16, 2023, 8:30 - 9:45 a.m. CEST Humanistic Burden of Rare Kidney Diseases: Understanding the Impact of IgAN and FSGS on Patients & Care-Partners Study (HONUS): US IgAN Results Update Session: Glomerular & Tubulo-interstitial Diseases Location & Time: Room 9; Friday, June 16, 2023, 5 - 6:15 p.m. CEST The Natural History of IgA Nephropathy in the German Chronic Kidney Disease (GCKD) Cohort Session: Glomerular & Tubulo-interstitial Diseases Location & Time: Room 2; Friday, June 16, 2023, 8:30 - 9:45 a.m. CEST The Natural History of FSGS in the German Chronic Kidney Disease (GCKD) Cohort Session: Glomerular & Tubulo-interstitial Diseases Location & Time: Room 9; Saturday, June 17, 2023, 8:30 - 9:45 a.m. CEST 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 US 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. FILSPARI™ (sparsentan) U.S. 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 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 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 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. 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 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 "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 include, but are not limited to, references to the efficacy, safety and tolerability pro sparsentan based on the preliminary data from the PROTECT interim analysis; and the relationship between reducing proteinuria in IgA nephropathy and preservation of kidney function. 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. The Company faces risks associated with market acceptance of its commercial products including efficacy, safety, price, reimbursement and benefit over competing therapies. 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. Specifically, the Company faces the risk that the results from the Phase 3 DUPLEX Study of sparsentan in FSGS will not serve as a basis for a regulatory submission for approval of sparsentan for FSGS and the risk that the Phase 3 PROTECT Study of sparsentan in IgAN will not demonstrate that sparsentan is safe or effective or serve as the basis for further approval of sparsentan. 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, including as a result of macroeconomic conditions; 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. 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 as included under the heading “Risk Factors” in the Company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2023, as filed with the Securities and Exchange Commission (“SEC”) on May 4, 2023, and other filings with the SEC. Media: Nivi Nehra Vice President, Corporate Communications 888-969-7879 mediarelations@travere.com Investors: Naomi Eichenbaum Vice President, Investor Relations 888-969-7879 IR@travere.com