This study has the purpose to answer how the Lipoprotein(a) (Lp(a)) level is distributed among Atherosclerotic cardiovascular disease (ASCVD) patients in Russia, and what is the connection between elevated levels of this parameter and the cardiovascular disease (CVD) risk.

Start Date15 Apr 2025

Sponsor / Collaborator

Novartis Pharmaceuticals Canada, Inc.

CTIS2023-504086-23-00

/ RecruitingPhase 3IIT

Efficacy and safety of bezafibrate 400 mg and bezafibrate 200 mg as adjunctive treatments in patients with primary biliary cholangitis and non-optimal biochemical response to ursodeoxycholic acid therapy: a 12-month, double-blind, randomized, placebo-controlled trial with a 12-month, double-blind, placebo-free extension phase - BEZURSO 2 - APHP220822

Start Date27 Mar 2025

Sponsor / Collaborator

Assistance Publique Hopitaux De Paris

NCT06443606

/ Not yet recruitingPhase 3IIT

Efficacy and Safety of Bezafibrate 400 mg and Bezafibrate 200 mg as Adjunctive Treatments in Patients With Primary Biliary Cholangitis and Non-optimal Biochemical Response to Ursodeoxycholic Acid Therapy: a 12-month, Double-blind, Randomized, Placebo-controlled Trial With a 12-month, Double-blind, Placebo-free Extension Phase.

Primary biliary cholangitis (PBC) is a rare chronic, progressive, cholestatic liver disease that leads to cirrhosis and its life-threatening complications if undertreated. Ursodeoxycholic acid (UDCA) is the standard-of-care therapy for PBC. However, patients with an inadequate biochemical response to UDCA according to the Paris-2 criteria are still at high-risk of poor clinical outcome. In this situation of biochemical resistance to UDCA, bezafibrate 400 mg/d given in association with UDCA has been shown to improve the symptoms, biochemical response (BEZURSO study), histologic features, and possibly long-term clinical outcome. However, it has been shown that even patients with an adequate response to UDCA but persistent elevation in biochemical markers of cholestasis or liver inflammation, including alkaline phosphatases (ALP), gamma-glutamyl transpeptidase (GGT), transaminases, or total bilirubin (i.e., non-optimal biochemical response) have still an increased risk of death or liver transplantation in the long term, thus defining the complete normalization of these markers as the new clinically-relevant target for PBC treatment. In parallel to these findings, bezafibrate 400 mg/d as a second-line therapy for PBC could be associated with potentially dose-related, muscle, kidney, or liver toxic effects, and whether bezafibrate 200 mg/d could have a better benefit/risk ratio in this disease-setting remains to be determined. Therefore, our aim is to evaluate the efficacy and safety of bezafibrate 400 mg and bezafibrate 200 mg as adjunctive treatments in PBC patients with non-optimal biochemical response to UDCA.

Start Date01 Sep 2024

Sponsor / Collaborator

Assistance Publique des Hôpitaux de Paris SA

100 Clinical Results associated with Bezafibrate

100 Translational Medicine associated with Bezafibrate

100 Patents (Medical) associated with Bezafibrate

3,908

Literatures (Medical) associated with Bezafibrate

01 Sep 2025·ENVIRONMENTAL POLLUTION

Pharmaceuticals in coastal sediments: validation of an ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry (UHPLC-TOF-MS) methodology

Article

Author: Pardal, Miguel A ; Leston, Sara ; Ramos, Fernando ; Freitas, Andreia ; Leite, Marta ; Cenáculo, Diogo ; Bessa, Filipa

Pharmaceutical contamination in coastal and marine sediments is an increasing environmental issue. Thousands of biologically active substances continuously enter aquatic ecosystems through wastewater discharge, agricultural runoff, and improper disposal. Due to their persistence and continuous release, these contaminants accumulate in various matrices, including water and sediments, posing long-term ecological risks. Their presence can disrupt microbial communities, bioaccumulate in marine organisms, and heighten the risks of chronic exposure and antimicrobial resistance. To safeguard human, animal, and environmental health, it is crucial to develop accurate methodologies to understand pharmaceutical occurrence profiles and monitor their presence in coastal ecosystems. This study describes the development and validation of a sensitive UHPLC-TOF-MS method for screening and confirming pharmaceuticals in coastal sediments, following Commission Implementing Regulation (EU) 2021/808. Thirty analytes were targeted and evaluated for key performance parameters, including selectivity and sensitivity, linearity, repeatability, reproducibility, trueness, limit of detection (LOD), and limit of quantification (LOQ). Data analysis demonstrated high selectivity and sensitivity, with LODs ranging from 0.02 to 0.23 ng/g and LOQs from 0.06 to 0.69 ng/g. Recovery values at the LOD level ranged from 74.3 % for irbesartan to 115.4 % for indapamide, while repeatability and reproducibility were under 19.5 % and 29.2 %, respectively. All performance criteria met the requirements outlined in European guidelines. To evaluate the method's robustness, it was applied to 12 sediment samples collected from an estuary, with irbesartan detected in 5 samples.

01 Aug 2025·WATER RESEARCH

Removal of PFAS and pharmaceuticals from municipal wastewater using a novel β-cyclodextrin adsorbent over distinct contact times

Article

Author: Packman, Aaron I ; Shapiro, Emma F ; Cifuentes, Edwin Saavedra ; Lin, Zhi-Wei ; Barajas-Rodriguez, Francisco J ; Gwinn, Rosa ; Dichtel, William R

Conventional adsorbents applied in wastewater treatment are ineffective at removing trace organic contaminants (TrOCs), including per and poly-fluoroalkyl substances (PFAS) and pharmaceuticals. Cross-linked β-cyclodextrin (β-CD) polymer adsorbents have demonstrated efficient removal of TrOCs and exhibit rapid kinetics and high adsorption capacity in wastewater. We evaluate the removal of a mixture of contaminants from wastewater by a styrene functionalized β-CD adsorbent (StyDex) through rapid small-scale column tests (RSSCTs). We found the kinetics observed in batch adsorption tests are maintained in RSSCTs. However, batch sorption kinetic constants did not match column breakthrough kinetics, due to an inability to describe complex flow-through behaviors. We correlated both batch kinetic constants and treatable bed volumes with hydrophobicity of target compounds, where PFOA and PFHxS had the highest affinity for StyDex in batch tests and the latest breakthroughs in RSSCTs. Breakthrough curves of five of the seven TrOCs were not affected by change in contact time. Conversely, decreasing the contact time led to earlier breakthrough of contaminants with the highest sorption affinity to StyDex: longer chained and sulfonated PFAS compounds. These effects were isolated in two-component competitive sorption experiments between PFOA and PFBA, and we observed the same preferential sorption of hydrophobic compounds identified in the multi-component mixture. Additionally, competitive adsorption-desorption increased with increasing contact times. We discuss how these findings are crucial for scale-up and large-scale testing of novel sorbents.

01 Aug 2025·FOOD CHEMISTRY

Investigation into the effects of acute heat stress on stress level, meat quality, myofibrillar proteins properties and serum metabolites release of Muscovy ducks (Cairina moschata)

Article

Author: Huang, Tianran ; Xiao, Mengchao ; Huang, Jichao ; Li, Zimu ; Zhu, Zongshuai ; Huang, Ming

This study systematically investigated the effects of acute heat stress (AHS) on Muscovy ducks, focusing on plasma stress indicators, meat quality, myofibrillar proteins (MPs) properties, and serum metabolite profiles. AHS significantly elevated stress level, impairing meat quality, as evidenced by higher L* value, shear force, drip loss, and cooking loss (P < 0.05). It also induced MPs oxidation and aggregation, reflected by elevated carbonyl content, turbidity, zeta potential, and particle size. MPs structural alterations were confirmed by fluorescence quenching and increased exposure of hydrophobic groups. Correlation analysis revealed strong associations between physicochemical changes and MPs oxidation. Metabolomic analysis identified 161 and 105 differential metabolites in the CON vs. LS and CON vs. SS comparisons, respectively, involving 25 metabolic pathways related to energy, amino acids, and fatty acids. These findings provide novel insights into the molecular pathways of AHS-induced meat quality deterioration and reveal potential intervention timing for the poultry industry.

News (Medical) associated with Bezafibrate

30 Apr 2025

·www.globenewswire.com

Intercept Announces Data to be Presented at Digestive Disease Week 2025

Abstracts include a presidential plenary-selected Phase 2 study evaluating the combination of obeticholic acid and bezafibrate in PBC, along with 10 other abstractsMORRISTOWN, N.J., April 30, 2025 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc. (Intercept), part of the Alfasigma Group, today announced 11 submitted abstracts have been accepted for presentation at Digestive Disease Week 2025, including oral presentations of data from a Phase 2 study evaluating the combination of obeticholic acid and bezafibrate in PBC, and investigational data for INT-787, a next-generation FXR agonist. The conference will be held from May 3-6 in San Diego. The abstracts showcase the Company’s breadth of research in the gastrointestinal (GI) and hepatology therapeutic areas. The data encompass multiple areas of high unmet need, including primary biliary cholangitis (PBC); primary sclerosing cholangitis (PSC); severe alcohol-associated hepatitis (sAH), a liver disease increasing in prevalence, especially among women; and chronic intestinal pseudo-obstruction (CIPO), a rare condition characterized by severe impairment of intestinal activity. “We look forward to sharing details of our clinical-development program progress with the scientific community, including our ongoing Phase 2 study of a potential first-in-class treatment for severe alcohol-associated hepatitis,” said Sangeeta Sawhney, M.D., Senior Vice President, Global Head, GI Therapeutic Area, Alfasigma. “We're also going to share the first six-year data for a second-line therapy for PBC, which gives insights into long-term safety and effectiveness." Presentations by Intercept and Alfasigma at DDW 2025: Oral Presentations “COMBINED EFFECT OF OBETICHOLIC ACID AND BEZAFIBRATE IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS AND INADEQUATE RESPONSE OR INTOLERANCE TO URSODEOXYCHOLIC ACID: 6-MONTH RESULTS FROM A PHASE 2 TRIAL” (Presentation #4)Session: AASLD Presidential PlenarySaturday, May 3, 9:15 AM ETChristophe Corpechot, Vaclav Hejda, Heng Zou, Antonio Civitarese, Alejandra Villamil, Frederik Nevens “FXR AGONIST INT-787 INHIBITS INFLAMMATION, FIBROSIS, SENESCENCE, AND APOPTOSIS ARREST IN HUMAN CHOLANGIOCYTES MODELING PSC” (Presentation #879)Session: Cutting-Edge Insights into PSC: From Mechanisms to TherapiesMonday, May 5, 4:45 PM ETFrancesca De Franco, Daniela Passeri, Sanjay Kansra, Luciano Adorini, Mary Erickson, Roberto Pellicciari Poster Presentations “OBETICHOLIC ACID NORMALIZES INFLAMMATORY BIOMARKERS IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS” (Poster #Sa1500)Session: Liver Inflammation and ImmunobiologySaturday, May 3, 12:30 PM ETDavid E. Jones, Christopher L. Bowlus, Arash Thranian, Mary Erickson, Jing Li, Christopher Gasink, Robert G. Gish “US POPULATION–BASED EPIDEMIOLOGY OF PRIMARY BILIARY CHOLANGITIS: EXAMINATION OF PATIENT CHARACTERISTICS AND INCIDENCE OF HEPATIC OUTCOMES IN A US HEALTHCARE CLAIMS DATABASE” (Poster #Su1675)Session: Health Disparities in Patients with Liver DiseaseSunday, May 4, 12:30 PM ETAparna Goel, Bridget L. Balkaran, Chris White, Radhika Nair, Anne Chiplin, Jing Li, Jayashri Desai, Joanna P. MacEwan “REAL-WORLD ADHERENCE TO OBETICHOLIC ACID THERAPY FOR PRIMARY BILIARY CHOLANGITIS” (Poster #Mo1626)Session: Human and Experimental Cholestatic and Autoimmune Liver DiseasesMonday, May 5, 12:30 PM ETRobert G. Gish, Joanna P. MacEwan, Jennifer Hernandez, Radhika Nair, Jing Li, Darren Wheeler, Anh Singhania, Leona Bessonova “PATIENTS WITHOUT BASELINE PRURITUS WHO INITIATE TREATMENT WITH OCA HAVE SIMILAR RISK OF DEVELOPING TREATMENT-EMERGENT PRURITUS AS THOSE WHO ARE NOT ON TREATMENT WITH OCA” (Poster #Mo1618)Session: Human and Experimental Cholestatic and Autoimmune Liver DiseasesMonday, May 5, 12:30 PM ETDavid Jones, Aparna Goel, Ann Moore, Jing Li, Darren Wheeler, Christopher White, and David W. Victor III “STABILIZATION OF ENHANCED LIVER FIBROSIS AND LIVER STIFFNESS MEASURES IN THE OPEN-LABEL EXTENSION OF THE PHASE 3 POISE TRIAL OF OBETICHOLIC ACID FOR THE TREATMENT OF PRIMARY BILIARY CHOLANGITIS” (Poster #Mo1667)Session: Non-Invasive Assessment of Liver DiseaseMonday, May 5, 12:30 PM ET Robert G. Gish, Darren Wheeler, Jing Li, Christopher Gasink, Alan Bonder “FARNESOID X RECEPTOR AGONIST INT-787 PROTECTS HUMAN LIVER ORGANOIDS FROM ALCOHOL-INDUCED INJURY” (Poster #Su1618)Session: Alcoholic-associated Liver Disease Including Alcohol-associated HepatitisSunday, May 4, 12:30 PM ETFrancesca De Franco, Daniela Passeri, Sanjay Kansra, Luciano Adorini, Mary Erickson, Roberto Pellicciari “FARNESOID X RECEPTOR AGONIST INT-787 EXHIBITS HIGH INTESTINAL LOCALIZATION” (Poster #Su1635)Session: Alcoholic-associated Liver Disease Including Alcohol-associated HepatitisSunday, May 4, 12:30 PM ETJennifer Burkey, Sanjay Kansra, Antonio Macchiarulo, Kenneth Brouwer, Luciano Adorini, Mary Erickson, Roberto Pellicciari “PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTION OF OBETICHOLIC ACID AND BEZAFIBRATE IN HEALTHY VOLUNTEERS” (Poster #Mo1628)Session: Human and Experimental Cholestatic and Autoimmune Liver DiseasesMonday, May 5, 12:30 PM ETJennifer Burkey, Karen Brown, Heng Zou, Jennifer Boston, Mary Erickson “DEVELOPMENT OF A DE NOVO CLINICAL OUTCOME ASSESSMENT FOR CHRONIC INTESTINAL PSEUDO-OBSTRUCTION" (Poster #Mo1258)Session: Patient Report and Clinical Outcomes: IBD, GERC, Functional Disorders, Other Monday, May 5, 12:30 PM ETMadhusudan Grover, Jan Tack, Sara Manzoni, Elena Pasquali, Valeria Scuderi, Vincenzo Stanghellini More information about these presentations will be made available after the respective embargoes, as set by the DDW organizers, are lifted for each presentation. A full list of sessions at DDW 2025 is available at www.ddw.org. Attendees of DDW can visit Intercept at booths #2011 and #2411 throughout the meeting. About Digestive Disease WeekDigestive Disease Week (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW is an in-person and online meeting from May 3-6, 2025. The meeting showcases more than 5,600 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. More information can be found at www.ddw.org. About Primary Biliary CholangitisPrimary biliary cholangitis (PBC) is a rare, progressive and chronic autoimmune disease that affects the bile ducts in the liver and is most prevalent (approximately 1 in 10,000) in women over the age of 40. PBC causes bile acid to build up in the liver, resulting in inflammation and scarring (fibrosis), which, if left untreated, can lead to cirrhosis, a liver transplant or death. About Severe Alcohol-Associated Hepatitis (sAH)Alcohol-related liver disease (ALD) as a cause of chronic liver disease is on the rise in the U.S. and is currently the leading indication for liver transplant listing overall in the U.S. Patients with severe alcohol-associated hepatitis (sAH) are now younger, with an increased representation of females compared to past decades, reflecting changing patterns of alcohol consumption in the U.S. Currently, there are no medicines with an approved indication to treat patients with sAH. About Primary Sclerosing CholangitisPrimary sclerosing cholangitis (PSC) is a rare, life-threatening, chronic cholestatic liver disease characterized by progressive destruction of bile ducts that leads to the development of cirrhosis and end-stage liver disease or cancer in a majority of patients. About the Investigational Obeticholic Acid-Bezafibrate CombinationIntercept has two ongoing Phase 2 studies (747-213 / NCT04594694, 747-214 / NCT05239468) that are exploring a range of therapeutic doses for the combination of obeticholic acid (OCA) and bezafibrate for the potential treatment of individuals with PBC. Obeticholic acid, a farnesoid X receptor (FXR) agonist, is marketed by Intercept as OCALIVA in the United States for the treatment of PBC (see below for full indication and Important Safety Information). Bezafibrate, a pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist, is not approved in the United States for any indication. FXR and PPAR are distinct pathways that each play a role in PBC. Simultaneously targeting both pathways may offer the greatest potential to impact bile acid synthesis, metabolism, and clearance that underly cholestatic liver diseases. Published studies establish a clinical proof-of-concept which suggests that the combination of obeticholic acid and bezafibrate may provide additive clinical efficacy and tolerability benefits in the treatment of PBC. Obeticholic acid-bezafibrate combination therapy is investigational; safety and efficacy have not been established. About OCALIVA (obeticholic acid)OCALIVA, a farnesoid X receptor (FXR) agonist, is indicated for the treatment of adult patients with primary biliary cholangitis (PBC) without cirrhosis orwith compensated cirrhosis who do not have evidence of portal hypertension, either in combination with ursodeoxycholic acid (UDCA) with an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA. This indication is approved under accelerated approval based on a reduction in alkaline phosphatase (ALP). An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. IMPORTANT SAFETY INFORMATION WARNING: HEPATIC DECOMPENSATION AND FAILURE IN PRIMARY BILIARY CHOLANGITIS PATIENTS WITH CIRRHOSIS Hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, have been reported with OCALIVA treatment in primary biliary cholangitis (PBC) patients with either compensated or decompensated cirrhosis. OCALIVA is contraindicated in PBC patients with decompensated cirrhosis, a prior decompensation event, or with compensated cirrhosis who have evidence of portal hypertension. Permanently discontinue OCALIVA in patients who develop laboratory or clinical evidence of hepatic decompensation; have compensated cirrhosis and develop evidence of portal hypertension, or experience clinically significant hepatic adverse reactions while on treatment. Contraindications OCALIVA is contraindicated in patients with: decompensated cirrhosis (e.g., Child-Pugh Class B or C) or a prior decompensation eventcompensated cirrhosis who have evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia)complete biliary obstruction Warnings and Precautions Hepatic Decompensation and Failure in PBC Patients with Cirrhosis Hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, have been reported with OCALIVA treatment in PBC patients with cirrhosis, either compensated or decompensated. Among post-marketing cases reporting it, median time to hepatic decompensation (e.g., new onset ascites) was four months for patients with compensated cirrhosis; median time to a new decompensation event (e.g., hepatic encephalopathy) was 2.5 months for patients with decompensated cirrhosis. Some of these cases occurred in patients with decompensated cirrhosis when they were treated with higher than the recommended dosage for that patient population; however, cases of hepatic decompensation and failure have continued to be reported in patients with decompensated cirrhosis even when they received the recommended dosage. Hepatotoxicity was observed in the OCALIVA clinical trials. A dose-response relationship was observed for the occurrence of hepatic adverse reactions including jaundice, worsening ascites, and primary biliary cholangitis flare with dosages of OCALIVA of 10 mg once daily to 50 mg once daily (up to 5-times the highest recommended dosage), as early as one month after starting treatment with OCALIVA in two 3-month, placebo-controlled clinical trials in patients with primarily early stage PBC. Routinely monitor patients for progression of PBC, including hepatic adverse reactions, with laboratory and clinical assessments to determine whether drug discontinuation is needed. Closely monitor patients with compensated cirrhosis, concomitant hepatic disease (e.g., autoimmune hepatitis, alcoholic liver disease), and/or with severe intercurrent illness for new evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia), or increases above the upper limit of normal in total bilirubin, direct bilirubin, or prothrombin time to determine whether drug discontinuation is needed. Permanently discontinue OCALIVA in patients who develop laboratory or clinical evidence of hepatic decompensation (e.g., ascites, jaundice, variceal bleeding, hepatic encephalopathy), have compensated cirrhosis and develop evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia), experience clinically significant hepatic adverse reactions, or develop complete biliary obstruction. If severe intercurrent illness occurs, interrupt treatment with OCALIVA and monitor the patient’s liver function. After resolution of the intercurrent illness, consider the potential risks and benefits of restarting OCALIVA treatment. Severe Pruritus Severe pruritus was reported in 23% of patients in the OCALIVA 10 mg arm, 19% of patients in the OCALIVA titration arm, and 7% of patients in the placebo arm in a 12-month double-blind randomized controlled clinical trial of 216 patients. Severe pruritus was defined as intense or widespread itching, interfering with activities of daily living, or causing severe sleep disturbance, or intolerable discomfort, and typically requiring medical interventions. Consider clinical evaluation of patients with new onset or worsening severe pruritus. Management strategies include the addition of bile acid binding resins or antihistamines, OCALIVA dosage reduction, and/or temporary interruption of OCALIVA dosing. Reduction in HDL-C Patients with PBC generally exhibit hyperlipidemia characterized by a significant elevation in total cholesterol primarily due to increased levels of high-density lipoprotein-cholesterol (HDL-C). Dose-dependent reductions from baseline in mean HDL-C levels were observed at 2 weeks in OCALIVA-treated patients, 20% and 9% in the 10 mg and titration arms, respectively, compared to 2% in the placebo arm. Monitor patients for changes in serum lipid levels during treatment. For patients who do not respond to OCALIVA after one year at the highest recommended dosage that can be tolerated (maximum of 10 mg once daily), and who experience a reduction in HDL-C, weigh the potential risks against the benefits of continuing treatment. Adverse Reactions The most common adverse reactions (≥5%) are pruritus, fatigue, abdominal pain and discomfort, rash, oropharyngeal pain, dizziness, constipation, arthralgia, thyroid function abnormality, and eczema. Drug Interactions Bile Acid Binding Resins Bile acid binding resins such as cholestyramine, colestipol, or colesevelam adsorb and reduce bile acid absorption and may reduce the absorption, systemic exposure, and efficacy of OCALIVA. If taking a bile acid binding resin, take OCALIVA at least four hours before or four hours after taking the bile acid binding resin, or at as great an interval as possible.Warfarin The International Normalized Ratio (INR) decreased following coadministration of warfarin and OCALIVA. Monitor INR and adjust the dose of warfarin, as needed, to maintain the target INR range when co-administering OCALIVA and warfarin.CYP1A2 Substrates with Narrow Therapeutic Index Obeticholic acid may increase the exposure to concomitant drugs that are CYP1A2 substrates. Therapeutic monitoring of CYP1A2 substrates with a narrow therapeutic index (e.g., theophylline and tizanidine) is recommended when co-administered with OCALIVA.Inhibitors of Bile Salt Efflux Pump Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP) such as cyclosporine. Concomitant medications that inhibit canalicular membrane bile acid transporters such as the BSEP may exacerbate accumulation of conjugated bile salts including taurine conjugate of obeticholic acid in the liver and result in clinical symptoms. If concomitant use is deemed necessary, monitor serum transaminases and bilirubin. Please click here for Full Prescribing Information, including boxed WARNING. To report SUSPECTED ADVERSE REACTIONS, contact Intercept Pharmaceuticals, Inc. at 1-844-782-ICPT or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. About InterceptIntercept, part of the Alfasigma Group since 2023, focuses on the development and commercialization of novel therapeutics to treat serious liver and GI diseases, including primary biliary cholangitis (PBC) and severe alcohol-associated hepatitis (sAH). Intercept owns the commercial rights to OCALIVA in the U.S. market. For more information, please visit www.interceptpharma.com or connect with the Company on LinkedIn, and X (formerly Twitter). About Alfasigma Alfasigma is a global pharmaceutical company founded over 75 years ago in Italy, where it is headquartered (in Bologna and Milan). The Group operates in over 100 markets spanning Europe, North and South America, Asia, and Africa. It has offices in many countries, including Italy, the United States (US), Spain, Germany, Mexico, and China; production sites in Italy, Spain, and the US; and R&D labs in Italy (Pomezia and Bergamo). Alfasigma employs approximately 4,000 people dedicated to research, development, production, and distribution of medicinal products contributing to its mission to provide better health and a better quality of life for patients, caregivers, and healthcare providers. It focuses on three main therapeutic areas: Gastroenterology/Hepatology, Vascular, and Rheumatology. Its portfolio spans from primary care to specialty care, rare disease medications, and consumer health products, including medical foods and nutraceuticals. For more information, please visit www.alfasigma.com or connect with the Company on LinkedIn, ContactFor more information about Intercept, please contact: media@interceptpharma.com

Phase 2Clinical ResultAccelerated Approval

02 Oct 2024

·www.prnewswire.com

Ipsen's IQIRVO Approval Has Intensified the Primary Biliary Cholangitis Market Space | DelveInsight

The European Commission has granted conditional approval for Ipsen's IQIRVO (elafibranor) for the treatment of primary biliary cholangitis in adults, marking the first new therapy for this condition to be approved in the EU in almost ten years. With this approval, other companies such as CymaBay Therapeutics, Zydus Therapeutics, GlaxoSmithKline, and others also geared up to bring their candidates into the primary biliary cholangitis market. LAS VEGAS, Oct. 2, 2024 /PRNewswire/ -- Primary biliary cholangitis (PBC), previously referred to as primary biliary cirrhosis, is a long-term liver condition characterized by the gradual destruction of the small bile ducts within the liver, known as intrahepatic bile ducts. Over time, prolonged bile flow obstruction can result in cirrhosis and the development of portal hypertension. As per DelveInsight analysis, in 2023, the total diagnosed prevalent cases of primary biliary cholangitis in the 7MM were approximately 298K. These cases are projected to increase further during the forecast period (2024–2034). In 2023, the United States had the highest proportion of diagnosed prevalent cases of primary biliary cholangitis among the 7MM, comprising approximately 48% of the total cases. DelveInsight's epidemiology model for primary biliary cholangitis estimates a higher prevalence among females across the 7MM. Specifically, in the US in 2023, it suggests approximately 25K cases among males and 117K cases among females, indicating a female predominance. The primary treatment objectives are to reduce the progression rate of the disease and manage symptoms such as itching, osteoporosis, and dry eye/mouth (sicca syndrome). Liver transplantation remains the only life-saving option. Ursodeoxycholic acid (UDCA) is the main medication used to slow disease progression. Patients in the early stages often experience clinical, biochemical, and histological improvements. Studies suggest UDCA postpones the need for liver transplantation and extends survival, though its effectiveness in advanced stages like cirrhosis is uncertain. While initially approved by the US FDA for treating primary biliary cholangitis, UDCA now has generic versions available. The use of corticosteroids in patients without signs of autoimmune hepatitis remains a subject of ongoing research. Studies have shown that combining UDCA with dexamethasone can enhance the activity of the anion exchanger from two alternate promoters in liver cells in vitro. Budesonide is being considered due to its extensive first-pass hepatic metabolism, which may help minimize side effects. Corticosteroids may help relieve symptoms and improve biochemical and histological outcomes, though corticosteroid-induced osteoporosis is a major concern. The criteria for liver transplantation in patients with primary biliary cholangitis are generally the same as those for other chronic liver diseases. However, severe and unmanageable itching is a unique reason for considering a transplant. Fatigue, which may continue after transplantation, is not regarded as an indication for the procedure. Liver transplantation for PBC patients typically offers a better prognosis than for most other chronic liver diseases, with a 5-year survival rate of 84–87% and a 10-year survival rate of 79–84%. In May 2016, the US FDA granted accelerated approval for OCALIVA (obeticholic acid) as a treatment for primary biliary cholangitis. It is approved for use alongside UDCA in adults who do not respond adequately to UDCA, or as a standalone treatment for those who cannot tolerate UDCA. OCALIVA is a semi-synthetic bile acid analog with the chemical structure 6α-ethyl-chenodeoxycholic acid. OCALIVA remains the only approved second-line therapy for this condition. Later, in December 2016, the European Commission gave conditional approval for OCALIVA for the same uses—either in combination with UDCA or as monotherapy for adults unable to tolerate UDCA. Learn more about the FDA-approved primary biliary cholangitis drugs @ Drugs for Primary Biliary Cholangitis Treatment Recently, the European Commission has granted conditional approval for IQIRVO (elafibranor) 80mg tablets for treating primary biliary cholangitis. It can be used alongside ursodeoxycholic acid in adults who have an inadequate response to UDCA or as a standalone therapy for those who cannot tolerate UDCA. This decision follows a positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) on July 26, 2024, and the US FDA's Accelerated Approval granted on June 10, 2024. Elafibranor, a pioneering molecule, has been marketed and commercialized in the US by Ipsen under the brand name IQIRVO since June 2024. It was originally developed by GENFIT, from its discovery through the completion of a 52-week Phase III clinical trial. In 2021, Ipsen obtained exclusive global rights to elafibranor, except for China, Hong Kong, Taiwan, and Macau, through a licensing agreement with GENFIT. The EU approval was based on favorable outcomes from the Phase III ELATIVE trial, which demonstrated a 47% clinical benefit of IQIRVO combined with UDCA compared to placebo plus UDCA on the composite primary endpoint. The main objective for cholestasis response was defined as alkaline phosphatase (ALP) being less than 1.67 times the upper limit of normal (ULN), with a ≥15% reduction in ALP and total bilirubin levels within the normal range after one year. Additionally, the treatment showed a reduction in pruritus when compared to placebo. Additionally, in August 2024, Gilead Sciences, Inc. announced that the FDA has granted accelerated approval for LIVDELZI (seladelpar) to treat primary biliary cholangitis. This treatment can be used alongside ursodeoxycholic acid in adults who have not responded adequately to UDCA or as a standalone therapy for those unable to tolerate UDCA. Livdelzi is not advised for patients with or who develop decompensated cirrhosis. Seladelpar (MBX-8025) is a potent and selective PPARδ agonist, administered orally, and is currently being developed for patients with PBC who either do not respond to or cannot tolerate UDCA. In March 2024, Gilead Sciences completed its acquisition of CymaBay and announced the validation of a Marketing Authorization Application (MAA) for Seladelpar by the European Medicines Agency (EMA). Seladelpar has been granted Breakthrough Therapy Designation (BTD) by the US FDA, PRIME status by the EMA, and Orphan Drug Designation (ODD) from both agencies, which may accelerate the approval process. To know more about primary biliary cholangitis treatment options, visit @ New Treatment for Primary Biliary Cholangitis With this approval, several companies have also geared up to bring their lead assets into the market. The expected launch of emerging therapies, such as Saroglitazar Magnesium (Zydus Therapeutics), Linerixibat (GlaxoSmithKline), Setanaxib (Calliditas Therapeutics AB), Bezafibrate + obeticholic acid (Intercept Pharmaceuticals/Alfasigma), Volixibat (Mirum Pharmaceuticals), EP547 (Escient Pharmaceuticals), and others are expected to create a positive impact on the market. Other therapies in the early stages of the trial are also being developed. Discover which therapies are expected to grab major primary biliary cholangitis market share @ Primary Biliary Cholangitis Market Report Saroglitazar (LIPAGLYN) comprises two primary types of PPAR agonists: PPARα (alpha) and PPARγ (gamma). This medication simultaneously reduces lipid and glucose levels, effectively decreasing elevated triglycerides and blood sugar while enhancing insulin sensitivity. The US FDA has awarded Saroglitazar orphan drug designation (ODD) and fast track designation (FTD) for primary biliary cholangitis (PBC). It is presently undergoing Phase II/III trials for this condition. Linerixibat (GSK2330672) is a medication under development for patients with primary biliary cholangitis who suffer from itching. It is a small molecule inhibitor of the ileal bile acid transporter (IBAT) that is minimally absorbed and taken as an oral tablet. By preventing the reabsorption of bile acids in the small intestine, linerixibat lowers the levels of pruritic bile acids in the bloodstream. In 2019, the FDA designated it as an orphan drug (ODD). It is currently being evaluated in a Phase III trial for treating cholestatic pruritus in individuals with PBC. Discover more about drugs for primary biliary cholangitis in development @ Primary Biliary Cholangitis Clinical Trials The anticipated launch of these emerging therapies for primary biliary cholangitis are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the primary biliary cholangitis market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the primary biliary cholangitis market saw a significant emergence of a dominant treatment modality, valued at USD 1.1 billion in the 7MM. This modality likely reflects advancements in therapeutic approaches such as first-line agents like UDCA, second-line treatments like obeticholic acid, and potentially emerging biologics or combination therapies aiming to address the complex pathophysiology of PBC, thus enhancing patient outcomes and market share. DelveInsight's latest published market report titled as Primary Biliary Cholangitis Market Insight, Epidemiology, and Market Forecast – 2034 will help you to discover which market leader is going to capture the largest market share. The report provides comprehensive insights into the primary biliary cholangitis country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The primary biliary cholangitis market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Diagnosed Prevalent cases of Primary Biliary Cholangitis Gender-specific Diagnosed Prevalent cases of Primary Biliary Cholangitis Age-specific Diagnosed Prevalent cases of Primary Biliary Cholangitis The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM primary biliary cholangitis market. Highlights include: 11-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis up to 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this primary biliary cholangitis market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the primary biliary cholangitis market. Also, stay abreast of the mitigating factors to improve your market position in the primary biliary cholangitis therapeutic space. Related Reports Primary Biliary Cholangitis Pipeline Primary Biliary Cholangitis Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key PBC companies, including Genfit, Zydus Discovery, Ohara Pharmaceutical, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Novartis, CymaBay Therapeutics, among others. Primary Biliary Cholangitis Epidemiology Forecast Primary Biliary Cholangitis Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, and PBC epidemiology trends. Liver Cirrhosis Market Liver Cirrhosis Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key liver cirrhosis companies, including Madrigal Pharmaceuticals, Inc., Galectin Therapeutics Inc., Grifols Therapeutics LLC, CymaBay Therapeutics, Akero Therapeutics, Inc., NGM Biopharmaceuticals, Inc., Gilead Sciences, Novo Nordisk A/S, Cellaion, Promethera Therapeutics, Lipocine Inc., Bristol Myers Squibb, Prism Pharma, Ohara Pharmaceutical, Shionogi, among others. Liver Cirrhosis Pipeline Liver Cirrhosis Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key liver cirrhosis companies, including Versantis AG, Mirum Pharmaceuticals, Sagimet Biosciences, TenNor Therapeutics, Prism Pharma, Vedanta Biosciences, Intercept Pharmaceuticals, Boehringer Ingelheim, Ohara Pharmaceutical, Ocelot Bio, Calliditas Therapeutics, Galecto Biotech, Pharmicell, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 3Drug ApprovalOrphan DrugClinical ResultBreakthrough Therapy

26 Jul 2024

·www.fiercebiotech.com

Calliditas' liver disease trial hits primary endpoint after sweeping changes to design

Calliditas Therapeutics’ press release lacks details of the next steps for setanaxib in primary biliary cholangitis. Calliditas Therapeutics’ slimmed-down, truncated and rethought primary biliary cholangitis (PBC) drug has hit its primary endpoint. But the biotech, which changed the midphase trial to cut costs, only saw a positive trend on liver stiffness and reported a higher rate of treatment-related dropouts on the study drug.The Stockholm-based biotech set out in 2021 to enroll more than 300 patients in a 52-week phase 2b/3 trial. Management rethought the study late last year, dropping the phase 3 part, cutting the enrollment target to 70 and the duration to 24 weeks and switching the primary endpoint to reduction in the liver enzyme ALP. Calliditas made the changes to reduce its R&D costs for the trial for 2024 and 2025.This morning, Calliditas reported that the study met its revised primary endpoint. The trial ultimately compared two doses of setanaxib to placebo in 76 patients with PBC and elevated liver stiffness. More than 40% of participants took ursodeoxycholic acid and either Intercept Pharmaceuticals’ Ocaliva or the PPAR agonist bezafibrate during the study. Thirteen percent of subjects were on all three drugs.From baseline, Calliditas tracked improvements in ALP of 19% on the high dose and 14% on the low dose. The biotech said the changes in ALP, a liver enzyme that is raised in PBC patients, were statistically significant versus placebo at both doses. Calliditas named liver stiffness and fatigue as the two other measures to look out for on an earnings call in May. The biotech reported “positive trends on liver stiffness” in the phase 2 readout. The top-line data release makes no mention of fatigue.Setanaxib was generally well tolerated, according to Calliditas, with similar rates of treatment emergent adverse events (TEAEs) in the placebo and treatment cohorts. The frequency of TEAEs leading to study discontinuation was higher in patients receiving setanaxib compared to placebo.Calliditas’ press release lacks details of the next steps for setanaxib in PBC. The biotech did highlight two upcoming readouts in other indications. A phase 2, investigator-led idiopathic pulmonary fibrosis trial is scheduled to report results around the end of the year. Calliditas’ phase 2 Alport syndrome study is set to deliver data in 2025.The studies form part of a multifront R&D program that has seen setanaxib tested in a range of settings including head and neck cancer. The breadth of the program reflects Calliditas’ belief that the potential anti-fibrotic effects of setanaxib have applications in a range of indications.

Phase 2Clinical ResultPhase 3Clinical Trial Failure

100 Deals associated with Bezafibrate

External Link

KEGG	Wiki	ATC	Drug Bank
D01366	Bezafibrate	C10AB02	DB01393

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Hyperlipidemias	Japan	Kissei Pharmaceutical Co., Ltd.	15 Mar 1991
Hypercholesterolemia	Japan	Nipro Corp.	01 Jan 1978
Hyperlipidemia, Familial Combined	Japan	Nipro Corp.	01 Jan 1978
Hypertriglyceridemia	Japan	Nipro Corp.	01 Jan 1978

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04594694 (747-213, GlobeNewswire) Manual	Phase 2	Primary Biliary Cholangitis	75	bezafibrate 400 mg SR + OCA 5 mg titrated to 10 mg at week 4	pmkmzbjfsn(txzvaqcjsu) = dltyjypyxk jacwxqcdhm (zxrulfbhyr ) View more	Positive	18 May 2024
				bezafibrate 200 mg IR + OCA 5 mg titrated to 10 mg at week 4	pmkmzbjfsn(txzvaqcjsu) = dvwmimaous jacwxqcdhm (zxrulfbhyr ) View more
NCT02548832 (CTgov)	Phase 3	Dyslipidemias	36	Berberine (Berberine)	rnbspdxeiv(brwuwmcrwn) = gjistxpegu kwzxsyfyhj (mimpgodskm, 0.9) View more	-	24 Feb 2023
				Bezafibrate (Bezafibrate)	rnbspdxeiv(brwuwmcrwn) = djujkinrav kwzxsyfyhj (mimpgodskm, 0.4) View more
Japan PBC Study Group (EASL2022)	Not Applicable	albumin \| bilirubin	889	Bezafibrate and Ursodeoxycholic Acid	rzdynrtqhn(pvbmfosjuk) = qyhfyovloo pedwallefi (fauqufjcep )	Negative	23 Jun 2022
WCLC2021	Not Applicable	Non-Small Cell Lung Cancer	-	Fibrates	tbpgozwloq(rgkkhrgbab): HR = 0.86 (95% CI, 0.75 - 0.99), P-Value = 0.042	-	08 Sep 2021
				No Fibrates
EASD2020	Not Applicable	Glucose Intolerance	-	Bezafibrate 400 mg/die	cchwbwxsoh(ogfztclpmt) = vsxeigvmmu bqvpbospwj (alddraldjk ) View more	-	22 Sep 2020
EASL2020	Not Applicable	Primary Biliary Cholangitis Add-on	-	UDCA monotherapy	nefhwzdwsc(dmgxcafsov): aHR = 0.52 (95% CI, 0.43 - 0.63), P-Value = < 0.0001 View more	-	27 Aug 2020
				UDCA and BZF combination therapy
NCT02984982 (ODYSSEY J-IVUS, CTgov)	Phase 4	Acute Coronary Syndrome \| Coronary Artery Disease \| Hypercholesterolemia	206	Antiplatelets+Atorvastatin+Rosuvastatin+Bezafibrate+Ezetimibe+Anticoagulants (Standard of Care)	sascgfhxaw(cfhunlfxxy) = xvjmpfbzwc isetzbbaje (apvyjzikee, 0.97) View more	-	09 Sep 2019
				Antiplatelets+Atorvastatin+Rosuvastatin+Alirocumab SAR236553+Bezafibrate+Ezetimibe+Anticoagulants (Alirocumab)	sascgfhxaw(cfhunlfxxy) = ezfpgpjlnj isetzbbaje (apvyjzikee, 0.95) View more
EASL2019	Not Applicable	Primary Biliary Cholangitis First line	307	Bezafibrate + Ursodeoxycholic acid	svkdoefurh(ehbvbuhehh) = plwftniqmc ekojvfigvw (aimxnzccwe, 309 - 141)	-	12 Apr 2019
EASL2019	Not Applicable	Primary Biliary Cholangitis	54	UDCA	nqmbobkiax(raocxydusl) = qhvianykty tiplkmqkys (ankwnavfth ) View more	Negative	12 Apr 2019
				Bezafibrate	nqmbobkiax(raocxydusl) = cddohzhpyd tiplkmqkys (ankwnavfth ) View more
NCT01654731 (Pubmed \| Br Dent J \| N Engl J Med) Manual	Phase 3	Primary Biliary Cholangitis	100	Bezafibrate	cnccbstmar(acxepupuui) = njnexjyqje pkzmnfowdo (byvothenbc ) View more	Positive	07 Jun 2018
				Placebo	cnccbstmar(acxepupuui) = udztrhhfyk pkzmnfowdo (byvothenbc ) View more

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