- |||||||||| Ocaliva (obeticholic acid) / Intercept
OXYGEN-NUTRIENT MISMATCH: A NOVEL CONCEPT TO EXPLAIN THE MECHANISM OF ACTION OF OBETICHOLIC ACID IN NASH (Poster Hall - San Diego Convention Center) - Apr 25, 2022 - Abstract #DDW2022DDW_5883; It inversely reduced PV flow, consistent with an active hepatic artery buffering response. Thus, increased delivery of oxygen rich HA blood, coupled with reduced nutrient rich PV blood, provides a rational explanation for the beneficial effect OCA in NASH and suggests new therapeutic targets.
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20045 - How OCALIVA Can Take PBC Treatment Further (DDW Theater 1, Hall B2 - San Diego Convention Center) - Apr 25, 2022 - Abstract #DDW2022DDW_5177; Description: Join us for an informative presentation about taking the treatment of Primary Biliary Cholangitis (PBC) a step further. Learn about an approved treatment for patients with PBC.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, seladelpar (MBX-8025) / CymaBay
TREATMENT WITH SELADELPAR IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS (PBC) AND PRIOR EXPERIENCE WITH OBETICHOLIC ACID OR FIBRATES (Poster Hall - San Diego Convention Center) - Apr 25, 2022 - Abstract #DDW2022DDW_2862; P2, P3 AE of pruritus was noted in 7%, 15%, and 18% in the 10 mg, 5 mg, and Pbo groups, respectively. Conclusion : In PBC pts with prior treatment with OCA or fibrates and ALP ≥ 1.67xULN, seladelpar appeared to be safe, well tolerated and showed meaningful and dose dependant improvement in biochemical markers of cholestasis.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, Kybella (sodium deoxycholate) / Bayer, AbbVie
HIGH FAT DIET SHAPES GUT MICROBIOME AND ACCELERATES PROGRESSION FROM BARRETT ESOPHAGUS TO ADENOCARCINOMA VIA SYSTEMIC BILE ACIDS (Poster Hall - San Diego Convention Center) - Apr 25, 2022 - Abstract #DDW2022DDW_1052; We assessed the effect of bile acids on the EAC pathological progression and we focused on farnesoid-X-receptor (FXR), a nuclear BA receptor and an important modulator in BA metabolism, and on obeticholic acid (OCA), a selective FXR agonist...We suggest that this leads to an acceleration of carcinogenesis via FXR signaling specifically on progenitor cells. FXR-upregulation in BE tissue appears to be protective against effects of BA in the esophageal microenvironment since it ameliorates the dysplastic phenotype and could be a potential preventive target.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Trial initiation date: Obeticholic Acid for Prevention in Barrett's Esophagus (clinicaltrials.gov) - Apr 19, 2022 P2, N=30, Not yet recruiting, In addition, compound 18k could significantly reduce blood glucose levels in C57 BL/6 mice and stimulate GLP-1 secretion in NCI-H716 cells and C57 BL/6 mice. Initiation date: Apr 2022 --> Oct 2022
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Review, Journal: Primary biliary cholangitis: advances in understanding and management. (Pubmed Central) - Apr 12, 2022 Recent guidelines have emphasised the importance of risk stratification, targeted treatment of symptoms and early prioritisation for second line therapies. The review summarises recent major developments in our understanding of primary biliary cholangitis and its management.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, NN1213 / Novo Nordisk
Trial completion date, Trial primary completion date: Effect of Heavy Alcohol Consumption on Farnesoid X Receptor (FXR) Signaling (clinicaltrials.gov) - Apr 12, 2022 P=N/A, N=45, Recruiting, The review summarises recent major developments in our understanding of primary biliary cholangitis and its management. Trial completion date: Apr 2023 --> Nov 2024 | Trial primary completion date: Apr 2022 --> Nov 2022
- |||||||||| Ocaliva (obeticholic acid) / Intercept
AMINOTRANSFERASE IMPROVEMENTS IN PATIENTS WITH NON-ALCOHOLIC STEATOHEPATITIS ARE ASSOCIATED WITH FIBROSIS REGRESSION IN THE REGENERATE STUDY ([VIRTUAL]) - Mar 25, 2022 - Abstract #CDDW2022CDDW_219; Funding Agencies None Background The interim analysis of the REGENERATE study showed obeticholic acid (OCA) 25 mg treatment significantly improved liver histology in patients with nonalcoholic steatohepatitis (NASH) and fibrosis...Patients with reductions in ALT or AST were up to twice as likely to have fibrosis improvement than those whose ALT or AST increased. The REGENERATE study is ongoing and will continue through clinical outcomes for verification and description of clinical benefits of OCA in treatment of NASH.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, aldafermin (NGM282) / NGM Biopharma, lanifibranor (IVA337) / Inventiva
Spontaneous and drug-induced histological changes in nonalcoholic steatohepatitis: an assessment by meta-analysis of trials (Poster Area) - Mar 16, 2022 - Abstract #EASLILC2022EASL_ILC_1689; Planned clinical studies arewarranted to further evaluate these effects. Since semaglutide and pioglitazone appear to be more effective on NASH activity while aldafermin, lanifibranor and obeticholic acid perform better on the evolution of fibrosis, combination therapies should be assessed prospectively in subjects who are less likely to improve spontaneously over time, i.e. older patients with biochemically active disease.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Oxygen-nutrient mismatch: a novel concept to explain how Obeticholic acid benefits NASH treatment (Poster Area) - Mar 16, 2022 - Abstract #EASLILC2022EASL_ILC_1677; OCA in dose responsive manner increased HA flow rates and inversely reduced PV flow, consistent with an active hepatic artery buffering response. Thus, increased delivery of oxygen rich HA blood, coupled with reduced nutrient rich PV blood, provides a rational concept for the beneficial effect of chronic OCA in NASH.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
The identification and characterization of novel bile acid-derived Farnesoid X Receptor agonists (Poster Area) - Mar 16, 2022 - Abstract #EASLILC2022EASL_ILC_1582; The HFD+CCL4 model is therefore clinically relevant in terms of histopathological presentation and targets of NASH compounds. Work here suggests that novel compounds 1 and 2 may be able to achieve gene-specific FXR regulation due to their proposed differential coactivator usage and thus may be promising candidates worthy of further research.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
A multicentric study to estimate mortality and graft loss risk after liver transplantation (LT) in patients with recurrent primary biliary cholangitis (PBC) (Poster Area) - Mar 16, 2022 - Abstract #EASLILC2022EASL_ILC_771; Liver function tests and scores to evaluate response to ursodeoxycholic acid (UDCA) have been developed to monitor disease progression and evaluate the addition of second-line treatments before LT...At the time of rPBC,145 patients (63%)were receiving tacrolimus, and 78 (34%) with cyclosporine...Only two (1%) and 10 patients (4%) started secondline treatment with obeticholic acid and fibrates, respectively. Patients with rPBC and disease activity as indicated by standard PBC risk scores have impaired outcomes, supporting efforts to treat recurrent disease in similar ways to pre-transplant PBC.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Analyses of obeticholic acid treatment retention in UK patients based on medicine delivery data (Poster Area) - Mar 16, 2022 - Abstract #EASLILC2022EASL_ILC_758; Our findings suggest an association between dose order history categoryand retention on treatment, prompting further study into optimal systems of management and support for patients on OCA. Conclusions about drop-out should be madewith caution, as the analyses only consider product orders, disconnected from clinical characteristics.
- |||||||||| selonsertib (GS-4997) / Gilead, Victoza (liraglutide) / Novo Nordisk, Ocaliva (obeticholic acid) / Intercept
Journal, Gold standard: Non-alcoholic fatty liver disease and steatohepatitis: state-of-the-art on effective therapeutics based on the gold standard method for diagnosis. (Pubmed Central) - Mar 8, 2022 Other drugs including bicyclol, cysteamine bitartrate, L-carnitine, liraglutide, obeticholic acid, oligofructose, selonsertib, silymarin, and statins each had a single clinical study. There is an urgent need for further research in this field.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: NRF2 Activation in Autophagy Defects Suppresses a Pharmacological Transactivation of the Nuclear Receptor FXR. (Pubmed Central) - Feb 26, 2022 Obeticholic acid as a potent FXR agonist has been approved to treat primary biliary cholangitis and clinical trials for its use in the treatment of other liver diseases are underway...Finally, we demonstrate that NRF2 activation by the treatment with the food antioxidant butylated hydroxyanisole is necessary and sufficient to inhibit the pharmacological activation of FXR in vivo. These results reveal a novel function of the basal autophagy-NRF2 axis for the regulation of FXR transactivation, and shed light on a potential therapeutic strategy in metabolic disease.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Primary biliary cholangitis (Pubmed Central) - Feb 19, 2022 However, 30 % to 40 % of patients have an inadequate biochemical response to UDCA and continue to be at high-risk of complications. In this situation, second-line treatments, including obeticholic acid or fibrates, should be considered in association with UDCA.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Intestinal farnesoid X receptor signaling controls hepatic fatty acid oxidation. (Pubmed Central) - Feb 17, 2022 To explore the different roles of hepatic and intestinal FXR in liver FAO, FAO-associated metabolites, including acylcarnitines and fatty acids, and FXR target gene mRNAs were profiled using an integrated metabolomic and transcriptomic analysis in control (Fxr), liver-specific Fxr-null (Fxr) and intestine-specific Fxr-null (Fxr) mice, treated either with the FXR agonist obeticholic acid (OCA) or vehicle (VEH)...This mechanism was confirmed in experiments based on human recombinant FGF19 treatment and intestinal Fgf15 depleted mice. This study revealed an important role for the intestinal FXR-FGF15 pathway in hepatic FAO repression.
- |||||||||| Entyvio (vedolizumab) / Takeda
Review, Journal: Treatment of primary sclerosing cholangitis. (Pubmed Central) - Feb 9, 2022 Successful PSC therapy, however, will be most likely a personalized combination of different drugs plus endoscopic treatment. This review aims at offering an overview on the experimental pharmacological strategies currently exploited for PSC treatment.
- |||||||||| Review, Journal: Horizon scanning of therapeutic modalities for nonalcoholic steatohepatitis. (Pubmed Central) - Feb 2, 2022
Five ongoing RCTs (5/62, 8.06%) will investigate histological progression to cirrhosis, death, or liver-related clinical outcomes. In conclusion, some therapeutic modalities showed promising benefits, but further studies are warranted to find a definite treatment of NASH which prevents progression to cirrhosis and adverse liver outcomes.
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