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

NCT06488911 / Enrolling by invitationPhase 3

A Phase 3, Open-Label, Long-Term Safety Extension Study Evaluating the Safety and Tolerability of the Fixed-Dose Combination of Obeticholic Acid and Bezafibrate in Subjects With Primary Biliary Cholangitis

An Open Label Long-Term Study to Evaluate the Safety and Tolerability of the Fixed-Dose Combination (FDC) of Obeticholic Acid (OCA) and Bezafibrate (BZF) tablet in Subjects with Primary Biliary Cholangitis (PBC).

Start Date01 Jul 2024

Sponsor / Collaborator

Intercept Pharmaceuticals, Inc.

NCT05239468 / Active, not recruitingPhase 2

A Phase 2a, Double-Blind, Randomized, Active Controlled, Parallel Group Study Evaluating the Efficacy, Safety, and Tolerability of Bezafibrate Administered in Combination With Obeticholic Acid in Subjects With Primary Biliary Cholangitis

Study to determine the effect of the investigational drug bezafibrate (BZF) alone and in combination with the investigational drug obeticholic acid (OCA) in participants with Primary Biliary Cholangitis (PBC).

Start Date21 Mar 2022

Sponsor / Collaborator

Intercept Pharmaceuticals, Inc.

100 Clinical Results associated with Bezafibrate

100 Translational Medicine associated with Bezafibrate

100 Patents (Medical) associated with Bezafibrate

1,801

Literatures (Medical) associated with Bezafibrate

01 Nov 2024·ZEITSCHRIFT FUR GASTROENTEROLOGIE

Sub-optimal therapy of patients with primary biliary cholangitis (PBC) in the real-life stetting of the German PBC cohort

Article

Author: Müller, Tobias ; Hinz, Matthias ; Dikopoulos, Nektarios ; Kremer, Andreas E. ; Roeb, Elke ; Wiegand, Johannes ; Schattenberg, Jörn M. ; Reuken, Philipp A. ; Denk, Gerald ; Muche, Marion ; Tacke, Frank ; Greinert, Robin ; Michl, Patrick ; Bantel, Heike ; Grümmer, Harald ; Stein, Kerstin ; Trebicka, Jonel ; Piotrowski, Katja ; Naumann, Uwe ; Weber, Andreas ; Teufel, Andreas ; Böttler, Tobias ; Behrens, Rüdiger ; Ringelhan, Marc ; Hofmann, Wolf Peter ; Berg, Christoph ; Simon, Karl-Georg ; Sarrazin, Christoph ; Kautz, Achim ; Günther, Rainer ; Franke, Annegret ; Keitel, Verena ; Berg, Thomas ; Marquardt, Jens U. ; Köppe-Bauernfeind, Nicole ; Wissniowski, Thaddäus Till ; Zeuzem, Stefan ; Trautwein, Christian

Abstract:

Real-world data on the management of patients with primary biliary cholangitis (PBC) are so far scarce in Germany. Therefore, we aimed to establish a nationwide registry and describe the clinical characteristics and therapy of PBC patients.Three different cohorts defined as ursodeoxycholic acid (UDCA) responders, as inadequate responders according to Paris II criteria, and as newly diagnosed patients were prospectively recruited.This manuscript includes the baseline data of the project.In total, 33/77 (43%) contacted centres (58% of university hospitals, 38% of non-university hospitals, and 24% of private practices) recruited 515 patients including 204 UDCA responders, 221 inadequate responders to UDCA, and 90 newly diagnosed patients.All patients were treated with UDCA; however, a UDCA dosage below the recommended dosage of 13 mg/kg/d was observed in 38.5% of individuals after 12 months of treatment. UDCA dosages were lower in nonacademic compared to academic centres.Only 75/219 (38.5%) of inadequate responders to UDCA received a second-line therapy with obeticholic acid (OCA) and/or bezafibrate (BZF). OCA (13% vs. 4.5%) and BZF (14% vs. 6.5%) were significantly more often prescribed by academic vs. nonacademic centres.Pruritus (27% vs. 15.5%), fatigue (23% vs. 4.5%), and sicca syndrome (14% vs. 1%) were significantly more often reported by academic centres.The German PBC registry could be established, which indicates suboptimal therapy in a relevant proportion of patients and shows significant differences between academic and nonacademic centres. Results are fundamental to improving clinical management at different levels of care.

01 Nov 2024·INTERNATIONAL JOURNAL OF PHARMACEUTICS

Fabrication of osmotic pump tablets utilizing semisolid extrusion three-dimensional printing technology

Article

Author: Wang, Xiangyu ; Ji, Yang ; Fang, Dongyang ; Chen, Hao ; Gong, Ye ; Pan, Hao

The utilization of three-dimensional (3D) printing technology is prevalent in the fabrication of oral sustained release preparations; however, there is a lack of research on 3D-printed osmotic pump tablets. A 3D-printed core-shell structure bezafibrate osmotic pump tablet was developed based on the characteristics of rapid absorption and short half-life of bezafibrate, utilizing semisolid extrusion (SSE) 3D printing technology. First, the properties of different shell materials were investigated to define the composition of the shell, and ultimately, the optimal formulation was found to be ethyl cellulose:cellulose acetate:polyethylene glycol = 2:1:2. The formulation of the tablet core was defined based on the printing performance and release behavior. The formulation consisted of bezafibrate, lactis anhydrous, sodium bicarbonate, sodium alginate, polyethylene oxide and sodium dodecyl sulfate at a ratio of 400:400:300:80:50:50. The tablet was capable of achieving zero-order release. The physicochemical properties were also characterized. The pharmacokinetic data analysis indicated that there were no statistically significant differences in the pharmacokinetic parameters between the 3D-printed tablets and the reference listed drugs. There was a strong correlation between the in vitro and in vivo results for the 3D-printed tablets. The results showed that SSE printing is a practical approach for manufacturing osmotic pump tablets.

15 Oct 2024·Aging-US

Bezafibrate mitigates cardiac injury against coronary microembolization by preventing activation of p38 MAPK/NF-κB signaling

Article

Author: Wang, Wenfang ; Liu, Ruijie ; Li, Wenfeng

Coronary microembolization (CME)-induced inflammatory response and cardiomyocyte apoptosis are the main contributors to CME-associated myocardial dysfunction. Bezafibrate, a peroxisome proliferator-activated receptors (PPARs) agonist, has displayed various benefits in different types of diseases. However, it is unknown whether Bezafibrate possesses a protective effect in myocardial dysfunction against CME. In this study, we aimed to investigate the pharmacological function of Bezafibrate in CME-induced insults in myocardial injury and progressive cardiac dysfunction and explore the underlying mechanism. A CME model was established in rats, and cardiac function was detected. The levels of injury biomarkers in serum including CK-MB, AST, and LDH were determined using commercial kits, and pro-inflammatory mediators including TNF-α and IL-6 were detected using ELISA kits. Our results indicate that Bezafibrate improved cardiac function after CME induction. Bezafibrate reduced the release of myocardial injury indicators such as CK-MB, AST, and LDH in CME rats. We also found that Bezafibrate ameliorated oxidative stress by increasing the levels of the antioxidant GPx and the activity of SOD and reducing the levels of TBARS and the activity of NOX. Bezafibrate inhibited the expression of pro-inflammatory cytokines such as TNF-α and IL-6. Importantly, Bezafibrate was found to mitigate CME-induced myocardial apoptosis by increasing the expression of Bcl-2 and reducing the levels of Bax and cleaved caspase-3. Mechanistically, Bezafibrate could prevent the activation of p38 MAPK/NF-κB signaling. These findings suggest that Bezafibrate may be a candidate therapeutic agent for cardioprotection against CME in clinical applications.

News (Medical) associated with Bezafibrate

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

26 Jul 2024

·www.prnewswire.com

Calliditas announces positive TRANSFORM Phase 2b topline data in primary biliary cholangitis

STOCKHOLM, July 26, 2024 /PRNewswire/ -- Calliditas Therapeutics AB (NASDAQ: CALT) (STOCKHOLM: CALTX) ("Calliditas") today announced that the Phase 2b TRANSFORM trial met its primary endpoint, showing statistically significant improvement in ALP (Alkaline Phosphatase) for both doses tested versus placebo. The trial evaluated setanaxib, a NOX enzyme inhibitor, in patients with primary biliary cholangitis (PBC) and elevated liver stiffness. The TRANSFORM trial is a double-blind, randomized, placebo-controlled Phase 2b study investigating the effect of setanaxib 800 mg AM + 400 mg PM, ("1200 mg arm") and 800 mg BID ("1600 mg arm") over 24 weeks of treatment. The basis for the analysis consisted of a dataset of 76 patients with primary biliary cholangitis (PBC) and elevated liver stiffness. The treatment groups were relatively well-balanced with no clinically relevant differences between the groups observed at baseline. The result is particularly encouraging as over 40% of the trial population was on dual therapy, ie was receiving UDCA (ursodeoxycholic acid) and either Ocaliva (obeticholic acid) or Bezafibrate (PPAR agonist) as base therapy and 13% were receiving all three therapies during the study, reflecting setanaxib having clinically relevant incremental benefit beyond existing standard of care. Patients treated with setanaxib showed statistically significant improvements in the primary endpoint of ALP of 19% in the 1600mg arm and 14% in the 1200mg arm and showed positive trends on liver stiffness assessed by FibroScan® at 24 weeks. Setanaxib treatment was generally well tolerated with overall number of TEAEs (treatment emergent adverse events), as well as serious TEAEs, being similar between active treatment and placebo. The frequency of TEAEs leading to study discontinuation was higher in patients receiving active treatment compared to placebo. "It is very encouraging to see a statistically significant treatment effect in this hard-to-treat population which is already on multiple medications in this relatively small study," said Professor Dave Jones OBE; Director, NHIP Academy; Director, Newcastle Centre for Rare Disease; Professor of Liver Immunology, Newcastle University; and Honorary Consultant Hepatologist, Newcastle upon Tyne Hospitals. "These positive data provide further clinical evidence of the potential of setanaxib in multiple rare diseases, and we are very pleased that we now have additional positive clinical evidence in support of our unique, first in class NOX platform. We also look forward to the read out of the investigator led study in IPF as well as the ongoing study in Alport syndrome in due course," said CEO Renée Aguiar-Lucander. "I am delighted that we have seen statistically significant and clinically meaningful improvements in ALP with encouraging trends in other outcomes in this population of patients with PBC. I'd like to extend my thanks to investigators, clinical trial site staff, and most importantly patients, who have all contributed to this important study," said CMO Richard Philipson. The company is conducting additional clinical trials with setanaxib and is expecting the investigator led Phase 2 trial in IPF (idiopathic pulmonary fibrosis) to provide top line data in Q4 2024 / Q1, 2025. There is also an ongoing Phase 2 proof of concept trial in Alport syndrome, which is expected to deliver top line data in 2025. For further information, please contact: Åsa Hillsten, Head of IR & Sustainability, Calliditas Tel.: +46 76 403 35 43, Email: [email protected] The information was sent for publication, through the agency of the contact persons set out above, on July 26, 2024 at 08:00 a.m. CET. This information was brought to you by Cision The following files are available for download:

Phase 2Clinical Result

100 Deals associated with Bezafibrate

External Link

KEGG	Wiki	ATC	Drug Bank
D01366	Bezafibrate	C10AB02	DB01393

R&D Status

Approved

10 top approved records.

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

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Primary Biliary Cholangitis	Phase 3	US	Intercept Pharmaceuticals, Inc.	01 Jul 2024
Primary Biliary Cholangitis	Phase 3	AR	Intercept Pharmaceuticals, Inc.	01 Jul 2024
Primary Biliary Cholangitis	Phase 3	AU	Intercept Pharmaceuticals, Inc.	01 Jul 2024
Primary Biliary Cholangitis	Phase 3	BE	Intercept Pharmaceuticals, Inc.	01 Jul 2024
Primary Biliary Cholangitis	Phase 3	CA	Intercept Pharmaceuticals, Inc.	01 Jul 2024
Primary Biliary Cholangitis	Phase 3	HR	Intercept Pharmaceuticals, Inc.	01 Jul 2024
Primary Biliary Cholangitis	Phase 3	CZ	Intercept Pharmaceuticals, Inc.	01 Jul 2024
Primary Biliary Cholangitis	Phase 3	EE	Intercept Pharmaceuticals, Inc.	01 Jul 2024
Primary Biliary Cholangitis	Phase 3	FR	Intercept Pharmaceuticals, Inc.	01 Jul 2024
Primary Biliary Cholangitis	Phase 3	DE	Intercept Pharmaceuticals, Inc.	01 Jul 2024

Clinical Result

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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	prsuizjajq(cctoqlprpm) = gsmjrucfet kvkgckpbzz (qahxlmssee ) View more	Positive	18 May 2024
				bezafibrate 200 mg IR + OCA 5 mg titrated to 10 mg at week 4	prsuizjajq(cctoqlprpm) = vszcgpcyxt kvkgckpbzz (qahxlmssee ) View more
NCT02548832 (CTgov)	Phase 3	Hyperlipidemia, Familial Combined	36	Berberine (Berberine)	arsjkhquvv(wagptdwmlr) = imyxlyzrni yyfzwcefjp (bjtewmmvfp, udxiwhuktd - hlbzuypgxh) View more	-	24 Feb 2023
				Bezafibrate (Bezafibrate)	arsjkhquvv(wagptdwmlr) = muubchplhu yyfzwcefjp (bjtewmmvfp, upxyekaxug - ifgfmpimpx) View more
Japan PBC Study Group (EASL2022)	Not Applicable	albumin \| bilirubin	889	Bezafibrate and Ursodeoxycholic Acid	xbtysobcld(drffeuwwfl) = rdljsxxhyo tekzynjnco (yvfshttnpy )	Negative	23 Jun 2022
WCLC2021	Not Applicable	Non-Small Cell Lung Cancer	-	Fibrates	lqhqopaxzc(npqjuzauly): 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	ospovgeygt(mjvnqmuxyv) = vkzhdadujh lvpkekxcei (gmnahmljug ) View more	-	22 Sep 2020
EASL2020	Not Applicable	Primary Biliary Cholangitis Add-on	-	UDCA monotherapy	ngheflccho(tqqklsctds): 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)	vetinbrnuq(pebmhukuay) = wrcfgshvkl novjokalcf (mlruhqzbjj, uklsyuafce - wpsbmkhabv) View more	-	09 Sep 2019
				Antiplatelets+Atorvastatin+Rosuvastatin+Alirocumab SAR236553+Bezafibrate+Ezetimibe+Anticoagulants (Alirocumab)	vetinbrnuq(pebmhukuay) = eafepqpici novjokalcf (mlruhqzbjj, yfpklkwxmx - tkqnmmizpj) View more
POISE (EASL2019)	Not Applicable	Primary Biliary Cholangitis	16	Obeticholic acid	jqmxsdazkt(axzetcqmpp) = znoawwdvid bnpaopnexl (qpknogekxm, 275.0 - 408.4) View more	Positive	13 Apr 2019
				Bezafibrate	jqmxsdazkt(axzetcqmpp) = moyoldhalp bnpaopnexl (qpknogekxm, 275.0 - 408.4) View more
EASL2019	Not Applicable	Primary Biliary Cholangitis First line	307	Bezafibrate + Ursodeoxycholic acid	bvtdsnsdvw(ifdwhpactp) = qvqptstrwj tfktmbdzdr (spxuhaycvg, 309 - 141)	-	12 Apr 2019
EASL2019	Not Applicable	Primary Biliary Cholangitis	54	UDCA	gppcgvbeml(xekxxsmexu) = xlaswqjqhq jeyopphqqh (salrkjhsxz ) View more	Negative	12 Apr 2019
				Bezafibrate	gppcgvbeml(xekxxsmexu) = xkkypkerqc jeyopphqqh (salrkjhsxz ) View more

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