- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Farnesoid X Receptor Agonists as Therapeutic Target for Cardiometabolic Diseases. (Pubmed Central) - Sep 30, 2020
Farnesoid X Receptor (FXR), a metabolic nuclear receptor, are found to be activated by primary BAs such as chenodeoxycholic acid (CDCA), cholic acid (CA) and synthetic agonists such as obeticholic acid (OCA)...Recently, emerging evidence suggests that FXR agonists are functional for metabolic syndrome and cardiovascular diseases and are considered as a potential therapeutic agent. This review will discuss the pathological mechanism of cardiometabolic disease and reviews the potential mechanisms of FXR agonists in the treatment of cardiometabolic disease.
- |||||||||| nidufexor (LMB763) / Novartis
Journal: Nidufexor (LMB763), a Novel FXR Modulator for the Treatment of Nonalcoholic Steatohepatitis (NASH). (Pubmed Central) - Sep 26, 2020
Here, we report the discovery of a novel chemical series of non-bile acid FXR agonists based on a tricyclic dihydrochromenopyrazole core from which emerged nidufexor (LMB763), a compound with partial FXR agonistic activity in vitro and FXR-dependent gene modulation in vivo. Nidufexor has advanced to Phase 2 human clinical trials in patients with NASH and diabetic nephropathy.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Current and emerging pharmacotherapeutic interventions for the treatment of liver fibrosis. (Pubmed Central) - Sep 16, 2020
Significant advances have been made in the development of novel antifibrotic pharmacotherapeutics. The authors expect that the development of combinatorial therapies, which combine compounds that target various pathways of fibrosis progression, will have a major impact as future etiology-independent therapies.
- |||||||||| INT-767 / Intercept
[VIRTUAL] Composite targeting of nuclear receptors protects against diet-induced NAFLD (Poster Area) - Aug 31, 2020 - Abstract #EASLILCI2020EASL-ILC-I-2265;
These effects are mediated insulin resistance-, mitochondrial function-, lipid and cholesterol metabolism-related genes, in overlapping and complementary signalling cascades. Hence, the multiple targeting of selected bile acid-activated receptors may embody a novel putative therapeutic approach PTDC/MED- PAT/31882/2017, EU H2020 Marie Sklodowska-Curie 722619.
- |||||||||| INT-767 / Intercept
[VIRTUAL] INT 767 – A novel dual farnesoid-X receptor (FXR) and takeda G-protein-coupled receptor-5 (TGR5) agonist attenuates intestinal ischemia reperfusion injury (E-Poster Hall) - Aug 29, 2020 - Abstract #TTS2020TTS_894;
Hence, the multiple targeting of selected bile acid-activated receptors may embody a novel putative therapeutic approach PTDC/MED- PAT/31882/2017, EU H2020 Marie Sklodowska-Curie 722619. We demonstrated that intravenous treatment with a dual FXR/TGR5 agonist (INT-767) after onset of ischemia significantly decreased intestinal damage caused by IRI. These results show that FXR and TGR5 receptors are promising targets for intestinal graft protection. The ability to administer this substance intravenously greatly enhances the potential applicability for the frequent pathology of intestinal infarction as well as for transplantation.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Clinical, Review, Journal: NAFLD Epidemiology, Emerging Pharmacotherapy, Liver Transplantation Implications and the Trends in the United States. (Pubmed Central) - Aug 26, 2020
There are no approved pharmacological agents to treat steatohepatitis or advanced fibrosis but obeticholic acid recently has shown some promise in phase III trial...Recurrent nonalcoholic steatohepatitis after LT is not uncommon, and thus warrants primary and secondary prevention strategies through a multidisciplinary approach. Prevalence of NAFLD in a donor population is a unique and growing concern that limits the access to quality liver grafts.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Preclinical, Journal: Hesperidin alleviates cholestasis via activation of the farnesoid X receptor in vitro and in vivo. (Pubmed Central) - Aug 26, 2020
Recently obeticholic acid, a farnesoid X receptor (FXR) agonist, was FDA-approved to treat cholestatic liver diseases, providing a new therapeutic strategy for cholestasis...Furthermore, HP down-regulated enzymes involved in bile acid synthesis including cholesterol 7α-hydroxylase and sterol 27-hydroxylase. HP produced a protective effect against cholestasis via FXR activation, and may be an effective approach for the prevention and treatment of cholestatic liver diseases.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Trial completion date, Trial primary completion date: OCAPUSH: Obeticholic Acid in Morbidly Obese Patients and Healthy Volunteers (clinicaltrials.gov) - Aug 25, 2020
P1, N=40, Recruiting,
Abstracts will be released on Friday, October 9, 2020. Trial completion date: Oct 2019 --> Jun 2021 | Trial primary completion date: Oct 2019 --> Dec 2020
- |||||||||| Lacromid (bezafibrate) / Remedica
[VIRTUAL] Prospective study of therapeutic education (TE) designed with a multidisciplinary team and participation of patients to improve the adherence to treatment of the patients and their quality of life (QOL) (Poster Area) - Aug 22, 2020 - Abstract #EASLILCI2020EASL-ILC-I-2133;
Baseline characteristics (number of pts): isolated PBC (n=21), overlap syndrome with AIH (n=9), extra-hepatic AI signs (n=20); fibrosis: F0-F2 (n=25), F3 (n=2), cirrhosis (n=3) ; pruritus (n=2) ; treatment : UDCA (n=25), fibrate (n=6), budesonide (n=4), azathioprine (n=5)...New treatments after inclusion: UDCA (n=2), obeticholic acid (n=7), bezafibrate (n=5). Patients with PBC exhibit a good adherence to a therapeutic education program which was associated with improvement in QoL and pruritus.
- |||||||||| A3384 / Albireo, maralixibat (SHP625) / Mirum Pharma, Ocaliva (obeticholic acid) / Intercept
Clinical, Review, Journal: Adjuvant treatments for biliary atresia. (Pubmed Central) - Aug 11, 2020
Newer modalities such as antiviral therapy (AVT), immunoglobulin, FXR agonists (e.g., obeticholic acid), ileal bile acid transporter (IBAT) antagonists (e.g., maralixibat) remain unproven. This article reviews the current evidence for the efficacy of adjuvant medical therapy in BA.
- |||||||||| Lacromid (bezafibrate) / Remedica, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Review, Journal: Current and potential treatments for primary biliary cholangitis. (Pubmed Central) - Jul 29, 2020
Bezafibrate, a pan-peroxisome proliferator-activated receptor agonist, has been shown to ameliorate deranged bile acid homoeostasis and attenuate raised concentrations of liver enzymes associated with primary biliary cholangitis...Various therapeutic target bile acid homeostasis, immune dysfunction, and fibrogenetic pathways are being studied. A better understanding of the biochemical and clinical effects of the therapies in development bear discussion, both to guide the discovery of new therapies and to inform clinicians so that rational treatment regimens can be tailored to patients once they become available.
- |||||||||| semaglutide SC once-daily (NN9536) / Novo Nordisk
Journal: Current and new pharmacotherapy options for non-alcoholic steatohepatitis. (Pubmed Central) - Jul 21, 2020
Farnesoid X receptor (FXR) agonist (obeticholic acid [OCA]) significantly ameliorated hepatic fibrosis in NASH stage 2/3 fibrosis in an interim analysis of phase 3 trial...Selonsertib (apoptosis signaling kinase 1 inhibitor), emricasan (an irreversible pan-caspase inhibitor), and simtsuzumab (a monoclonal antibody against lysyl oxidase-like 2) were discontinued because of no efficacy over placebo...Among antidiabetic agents, semaglutide, a novel GLP-1 RA, is ongoing for NASH stage 1-3 fibrosis in a phase 2 trial. Furthermore, the combination of GLP-RA/glucagon receptor agonist and GLP-RA/gastrointestinal peptide agonist are promising future options.
- |||||||||| Lacromid (bezafibrate) / Remedica
[VIRTUAL] PRIMARY BILIARY CHOLANGITIS WITH FEATURES OF AUTOIMMUNE HEPATITIS IN AN PATIENT WITH HIV INFECTION (Poster Exhibition) - Jul 19, 2020 - Abstract #UEGW2020UEGW_5639;
Clinical Case Summary: We present a 59 year-old man with known HIV infection since 2013, treated with abacavir, dolutegravir and lamivudine since then...Due to incomplete response to UDCA at 12 months (ALP 541 to 261 U/L) and since data concerning obeticholic acid with concomitant antiretroviral therapy were lacking, bezafibrate was added...It is believed that these autoimmunity phenomena occur in the context of inflammatory immune reconstitution induced by antiretroviral therapy. Therefore, in an era of generalization of this therapy, it is important to remain alert to this entity and its diagnostic and therapeutic challenges.
- |||||||||| Lacromid (bezafibrate) / Remedica
[VIRTUAL] PRIMARY BILIARY CHOLANGITIS WITH FEATURES OF AUTOIMMUNE HEPATITIS IN AN PATIENT WITH HIV INFECTION (Poster Exhibition) - Jul 19, 2020 - Abstract #UEGW2020UEGW_3663;
Clinical Case Summary: We present a 59 year-old man with known HIV infection since 2013, treated with abacavir, dolutegravir and lamivudine since then...Due to incomplete response to UDCA at 12 months (ALP 541 to 261 U/L) and since data concerning obeticholic acid with concomitant antiretroviral therapy were lacking, bezafibrate was added...It is believed that these autoimmunity phenomena occur in the context of inflammatory immune reconstitution induced by antiretroviral therapy. Therefore, in an era of generalization of this therapy, it is important to remain alert to this entity and its diagnostic and therapeutic challenges.
- |||||||||| Lacromid (bezafibrate) / Remedica
[VIRTUAL] PRIMARY BILIARY CHOLANGITIS WITH FEATURES OF AUTOIMMUNE HEPATITIS IN AN PATIENT WITH HIV INFECTION (Poster Exhibition) - Jul 19, 2020 - Abstract #UEGW2020UEGW_1679;
Clinical Case Summary: We present a 59 year-old man with known HIV infection since 2013, treated with abacavir, dolutegravir and lamivudine since then...Due to incomplete response to UDCA at 12 months (ALP 541 to 261 U/L) and since data concerning obeticholic acid with concomitant antiretroviral therapy were lacking, bezafibrate was added...It is believed that these autoimmunity phenomena occur in the context of inflammatory immune reconstitution induced by antiretroviral therapy. Therefore, in an era of generalization of this therapy, it is important to remain alert to this entity and its diagnostic and therapeutic challenges.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Update on Emerging Treatment Options for Primary Biliary Cholangitis. (Pubmed Central) - Jun 19, 2020
Obeticholic acid (OCA) was recently approved as adjunct therapy in PBC patients with inadequate response or intolerance to UDCA...Of these, fibrates, which have been used in Japan for over a decade, have produced promising results. Furthermore, as currently approved therapies for PBC do not address the potentially debilitating clinical symptoms of PBC such as pruritus and fatigue, supplemental therapy is often required for symptom control.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Primary Biliary Cholangitis and Bile Acid Farnesoid X Receptor Agonists. (Pubmed Central) - Jun 16, 2020
This has led to the identification of the role of the farnesoid x receptor (FXR) in cholestatic liver diseases and, consequently, to the development of obeticholic acid (OCA), a steroid FXR agonist that has been recently approved for the treatment of PBC...Therefore, the search for new therapeutic strategies for PBC has begun. This review, in addition to summarizing the current treatments for PBC, provides overview of the chemical characteristics of new steroid FXR agonist candidates that could represent a future perspective for the treatment of PBC.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Biomarker, Review, Journal: The challenges of primary biliary cholangitis: What is new and what needs to be done. (Pubmed Central) - Jun 4, 2020
The only approved second-line treatment is obeticholic acid...Strategies are needed to identify difficult-to-treat patients at an early disease stage, when new therapeutic approaches targeting immunologic pathways, in addition to bile acid-based therapies, may be effective. In conclusion, using interdisciplinary approaches, groundbreaking advances can be expected before long in respect to our understanding of the etiopathogenesis of PBC, with the ultimate aim of improving its treatment.
- |||||||||| bile acid cholic acid (INT-777) / Intercept
Journal: Bile Acids Signal via TGR5 to Activate Intestinal Stem Cells and Epithelial Regeneration. (Pubmed Central) - Jun 3, 2020
BAs promote regeneration of the intestinal epithelium via activation of TGR5 in ISCs, resulting in activation of SRC and YAP and activation of their target genes. Release of endogenous BAs in the intestinal lumen is sufficient to promote ISC renewal and proliferation in response to injury.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
[VIRTUAL] A translational mouse model for NASH and advanced fibrosis in association with atherosclerosis (Poster Area) - May 30, 2020 - Abstract #EASLILCI2020EASL-ILC-I-1414;
By adaptation of the fat content of the diet, either insulin resistance and adipose tissue inflammation (lard-based diet) or hepatic inflammation and fibrosis (milk-fat diet) can be emphasized. This represents a novel translational animal model of fibrosing NASH in association with atherosclerosis that can be used to investigate the effects of new drugs, alone (or drugs in combination).
- |||||||||| Triglide (fenofibrate) / Vectura, Shionogi, Ocaliva (obeticholic acid) / Intercept, Lacromid (bezafibrate) / Remedica
[VIRTUAL] Comparative effects of second-line therapy with obeticholic acid or fibrates in primary biliary cholangitis patients (Poster Area) - May 30, 2020 - Abstract #EASLILCI2020EASL-ILC-I-1023;
Second-line therapy with obeticholic acid or fibrates improve hepatic biochemistry with infrequent adverse events in patients with primary biliary cholangitis non- responders to UDCA. Fibrates are associated with higher decrease in alkaline phosphatase while obeticholic acid with higher transaminases improvement.
- |||||||||| INT-767 / Intercept
[VIRTUAL] Composite targeting of nuclear receptors protects against diet-induced NAFLD (Channel 3) - May 30, 2020 - Abstract #EASLILCI2020EASL-ILC-I-1018;
These effects are mediated through modulation of multiple inflammatory-, fibrogenic-, insulin resistance-, mitochondrial function-, lipid and cholesterol metabolism-related genes, in overlapping and complementary signalling cascades. Hence, the multiple targeting of selected bile acid-activated receptors may embody a novel putative therapeutic approach in preventing NAFLD.
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