- |||||||||| Ocaliva (obeticholic acid) / Intercept
Clinical, Journal: Long-term Obeticholic Acid Therapy Improves Histological Endpoints in Patients With Primary Biliary Cholangitis. (Pubmed Central) - Aug 20, 2021
P3
Additional studies are recommended to prospectively investigate these findings. A sub-analysis of data from the POISE study demonstrated that long-term OCA treatment in patients with PBC is associated with improvements or stabilization of disease features, including ductular injury, fibrosis, and collagen morphometry features (ClinicalTrials.gov no: NCT01473524 and EudraCT no: 2011-004728-36).
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: The pathogenesis, models and therapeutic advances of primary biliary cholangitis. (Pubmed Central) - Aug 20, 2021
In the last few years, as the learned more about the pathogenesis of PBC, more and more targets have been discovered, and multiple targeted drugs are being in developed. In this review, the pathogenesis, murine models and treatment strategies of PBC were summarized, and the current research status was discussed to provide insights for the further study of PBC.
- |||||||||| bezafibrate / Generic mfg.
[VIRTUAL] Autoimmune Hepatitis and Primary Biliary Cholangitis () - Aug 19, 2021 - Abstract #APDW2021APDW_696;
OCA increases risk of pruritis whereas bezafibrate has been demonstrated to have anti-pruritic properties. Additional phase 2 studies examining PPAR agonists show promise as second line therapies.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Obeticholic Acid for the Treatment of Nonalcoholic Steatohepatitis. (Pubmed Central) - Aug 14, 2021
N=50 --> 22 | Trial completion date: Dec 2022 --> Jul 2021 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2022 --> Jul 2021; Due to Ocaliva (obeticholic acid) US labeling update, the sponsor decided to terminate the study. No abstract available
- |||||||||| bile acid cholic acid (INT-777) / Intercept
Journal: Roux-en-Y gastrointestinal bypass promotes activation of TGR 5 and peptide YY. (Pubmed Central) - Aug 6, 2021
Validation of generalizability for safety and efficacy of NASH investigational agents in real-world populations is needed. Our study suggests that GBP up-regulated the expression of TGR5 in murine intestines, and increased the levels of PYY, which further reduced food intake and decreased the body weight.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Obeticholic acid ameliorates obesity and hepatic steatosis by activating brown fat. (Pubmed Central) - Aug 5, 2021
In summary, OCA functioned as a BAT activator to help ameliorate obesity and maintain glucose homeostasis in db/db mice. The present results may provide a novel potential therapeutic approach to activate brown fat in patients with obesity and other metabolic disorders.
- |||||||||| bile acid cholic acid (INT-777) / Intercept
Journal: Central anorexigenic actions of bile acids are mediated by TGR5. (Pubmed Central) - Aug 4, 2021
Notably, peripheral or central administration of a BA mix or a TGR5-specific BA mimetic (INT-777) exerted an anorexigenic effect in wild-type mice, while whole-body, neuron-specific or agouti-related peptide neuronal TGR5 deletion caused a significant increase in food intake...In vitro studies demonstrated that activation of the Rho-ROCK-actin-remodelling pathway decreases orexigenic agouti-related peptide/neuropeptide Y (AgRP/NPY) release in a TGR5-dependent manner. Taken together, these data identify a signalling cascade by which BAs exert acute effects at the transition between fasting and feeding and prime the switch towards satiety, unveiling a previously unrecognized role of physiological feedback mediated by BAs in the central nervous system.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Emerging therapies for PBC. (Pubmed Central) - Jul 28, 2021
New therapies are desperately needed, but evaluation has been limited by the fact that the disease is heterogeneous, hard end points take years to develop, and there are different criteria in use for determining therapeutic response based on surrogate biomarkers. Fibrates appear to be the most promising new therapy and have beneficially affected surrogate end points and are beginning to show improvement in clinical end points.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Obeticholic acid-a new therapy in PBC and NASH. (Pubmed Central) - Jul 17, 2021
New FXR agonists with a lower rate of side effects are being developed and trialed. Combination therapy with other agents may offer increased efficacy.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Preclinical, Journal: Metabolomic Study of High-Fat Diet-Induced Obese (DIO) and DIO Plus CCl-Induced NASH Mice and the Effect of Obeticholic Acid. (Pubmed Central) - Jul 4, 2021
The correlation analysis of metabolite levels and clinical parameters showed that phosphatidylcholines were negatively associated with serum alanine aminotransferase, aspartate aminotransferase, NAFLD activity score, and fibrosis score, while lysophosphatidylcholines, sphingomyelins, amino acids, and acylcarnitines shared the reverse pattern. Our study investigated metabolic alteration among control, NAFLD model, and OCA treatment groups, providing preclinical information to understand the mechanism of NAFLD and amelioration of OCA.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Preclinical, Journal: Activation of FXR modulates SOCS3/Jak2/STAT3 signaling axis in a NASH-dependent hepatocellular carcinoma animal model. (Pubmed Central) - Jul 2, 2021
Herein, we investigated the effect of obeticholic acid (OCA), as an FXR agonist, on NASH-associated HCC (NASH-HCC) animal model induced by diethylnitrosamine and high fat choline-deficient diet, exploring the potential impact on the suppressor of cytokine signaling 3 (SOCS3)/Janus kinase 2 (Jak2)/signal transducer and activator of transcription 3 (STAT3) pathway...In conclusion, our findings show that OCA attenuated the development and progression of NASH-dependent HCC possibly by interfering with SOCS3/Jak2/STAT3 pathway. These findings suggest the potential use of FXR activators in NASH-related disorders, even at later stages of the disease, to impede its progression to the more deteriorating HCC condition.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Preclinical, Journal: Isotschimgine alleviates nonalcoholic steatohepatitis and fibrosis via FXR agonism in mice. (Pubmed Central) - Jul 1, 2021
Farnesoid X receptor (FXR) agonist obeticholic acid (OCA) has emerged as a potential therapy for nonalcoholic fatty liver disease (NAFLD)...Mechanistically, ITG increased the expression of FXR target genes. These data suggest that ITG is an FXR agonist and may be developed as a novel therapy for NASH, hepatic fibrosis, or primary biliary cholangitis.
- |||||||||| bezafibrate / Generic mfg.
Journal: Diagnosis and treatment of primary biliary cholangitis. (Pubmed Central) - Jun 30, 2021
These data suggest that ITG is an FXR agonist and may be developed as a novel therapy for NASH, hepatic fibrosis, or primary biliary cholangitis. No abstract available
- |||||||||| bezafibrate / Generic mfg.
Review, Journal: An insight into the mechanism and molecular basis of dysfunctional immune response involved in cholestasis. (Pubmed Central) - Jun 30, 2021
Moreover, scarce reviews summarize the immune responses during cholestasis and the efficacy of therapies on immune response. The main purpose of this paper is to review the existing literature on dysfunctional immune response during cholestasis and the effect of treatment on immune response which may provide an insight for researchers and drug development.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: The role of farnesoid X receptor in metabolic diseases, and gastrointestinal and liver cancer. (Pubmed Central) - Jun 30, 2021
Hepatic FXR activation by obeticholic acid is currently used to treat primary biliary cholangitis...Modulating intestinal FXR signalling and altering BA metabolites are potential strategies for gastrointestinal and liver cancer prevention and treatment. In this Review, studies on the role of FXR in metabolic diseases and gastrointestinal and liver cancer are discussed, and the potential for development of targeted drugs are summarized.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Novel Insights of Primary Sclerosing Cholangitis and Primary Biliary Cholangitis (Pubmed Central) - Jun 24, 2021
Patient presentation and course can be diverse in PBC, and risk stratification is important for ensuring that all patients receive a personalized approach to their care. Medical therapy using ursodeoxycholic acid or obeticholic acid has an important role in reducing the progression to end-stage liver disease in PBC.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Pose Filter-based Ensemble Learning Enables Discovery of Orally Active, Nonsteroidal Farnesoid X Receptor Agonists. (Pubmed Central) - Jun 22, 2021
The low success rate of FXR agonists' R&D and the side effects of clinical candidates such as obeticholic acid make it urgent to discover new chemotypes...To provide insight into further structure-based lead optimization, we solved the crystal structure of hFXR complexed with compound XJ034 that uncovers a unique hydrogen bond between compound XJ034 and residue Y375. The current work highlights the power of our pose filter-based ensemble learning approach in term of scaffold hopping and provides a promising lead compound for further development.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Clinical, Journal: Reduction and Stabilization of Bilirubin With Obeticholic Acid Treatment in Patients With Primary Biliary Cholangitis. (Pubmed Central) - Jun 22, 2021
Obeticholic acid treatment was associated with significant reductions in total and direct bilirubin, particularly in patients with high baseline direct bilirubin. Because raised direct bilirubin levels, even within the normal range, are predictive of survival in primary biliary cholangitis, these results suggest substantial benefits of obeticholic acid in at-risk patients.
- |||||||||| EDP-305 / Enanta
Journal: A novel non-bile acid FXR agonist EDP-305 potently suppresses liver injury and fibrosis without worsening of ductular reaction. (Pubmed Central) - Jun 22, 2021
Because raised direct bilirubin levels, even within the normal range, are predictive of survival in primary biliary cholangitis, these results suggest substantial benefits of obeticholic acid in at-risk patients. EDP-305 potently improved pre-established liver injury and hepatic fibrosis in murine biliary and metabolic models of liver disease, supporting the clinical evaluation of EDP-305 in fibrotic liver diseases including cholangiopathies and NASH.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Primary Biliary Cholangitis management: controversies, perspectives, and daily practice implications from an expert panel. (Pubmed Central) - Jun 22, 2021
Six Italian experts selected the following topics as the most urgent to address in PBC management: diagnosis and natural history of PBC: as a portion of the subjects with isolated AMA, normal alkaline phosphatase levels and no symptoms of liver disease could have PBC by histology, defining how to manage and follow this population is crucial; role of liver biopsy: recent evidence suggests that biopsy may provide relevant information for risk stratification and prediction of UDCA response, possibly facilitating personalized approaches; risk stratification: the tools for risk stratification are well established, but some issues (e.g. bile acid dosage in routine practice) remain controversial; therapy: those in more advanced stages of development are nuclear receptor modulators and fibrates, but more data are needed to plan personalized strategies. In this manuscript, for each topic, current evidence, controversies, and future perspectives are summarized with the possible implications for clinical practice.
- |||||||||| icosabutate (NST-4016) / Abbott, NorthSea Therapeutics
Journal: Dual targeting of hepatic fibrosis and atherogenesis by icosabutate, an engineered eicosapentaenoic acid derivative. (Pubmed Central) - Jun 22, 2021
In this manuscript, for each topic, current evidence, controversies, and future perspectives are summarized with the possible implications for clinical practice. Icosabutate, a structurally-engineered EPA derivative, effectively attenuates both hepatic fibrosis and atherogenesis and offers an attractive therapeutic approach to both liver- and CV-related morbidity and mortality in NASH patients.
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