- |||||||||| Ocaliva (obeticholic acid) / Intercept
Spleen stiffness measurement predicts decompensation risk in primary biliary cholangitis (Poster Area) - Apr 12, 2023 - Abstract #EASLILC2023EASL_ILC_538;
Both LSM and SSM predict risk of decompensation in PBC patients. SSM >40 kPa is predictive of presence of varices and might be used in combination with LSM and platelet count to improve prediction of complications related to portal hypertension.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Bile acid nuclear receptor FXR participates in AKI to CKD transition through regulating G2/M arrest () - Mar 28, 2023 - Abstract #ISNWCN2023ISN_WCN_686;
Treatment was safe in patients with early-stage cirrhosis. Methods To investigate whether FXR would prevent the progression of AKI to CKD, wild-type mice treated with FXR agonist INT-747 and FXR gene knockout (KO) mice were executed to bilateral renal ischemic-reperfusion injury (bIRI, ischemia for 30 minutes at 37
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Enrollment change, Trial completion date, Trial termination, Trial primary completion date: CARE: Obeticholic Acid in Pediatric Subjects With Biliary Atresia (clinicaltrials.gov) - Mar 28, 2023
P2, N=7, Terminated,
N=32 --> 7 | Trial completion date: May 2025 --> Mar 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Jul 2023 --> Mar 2023; After extensive efforts to improve recruitment, it is deemed not feasible to enroll the requisite number of subjects to generate data needed to meet the study objectives. EMA Paediatric Committee agreed with the Sponsor to terminate this study.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, Mustargen (mechlorethamine) / Recordati
Suppression of Lung Nitrogen Mustard-induced Pulmonary Fibrosis, Oxidative Stress and Inflammatory Macrophage Activation by the Farnesoid X Receptor Agonist, Obeticholic Acid (Walter E. Washington Convention Center, Area F, Hall C (Lower Level)) - Mar 25, 2023 - Abstract #ATS2023ATS_7510;
These findings demonstrate that FXR plays a role in limiting NM-induced injury/fibrosis, oxidative stress, and inflammatory macrophage activation, processes key to the pathogenic response of the lung to mustard vesicants. Supported by NIH grants AR055073, ES005022 and ES007148.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
THE TRENDS AND INCIDENCE OF PRIMARY BILIARY CHOLANGITIS HOSPITALIZATIONS FROM 2012-2020 (South Hall A, Poster Hall - McCormick Place) - Mar 23, 2023 - Abstract #DDW2023DDW_7000;
However, other medications are available as second line treatments, including obeticholic acid (OCA) which was approved by the FDA for use in the United States in 2016...Hospitalizations post-OCA approval have increased by 1.17 times as compared to the years prior. While there was an upward trend in death rate, acute kidney failure, and portal hypertension across years, there was no significant difference in mLOS or other complications.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
NEW SAFETY AND EFFICACY ANALYSES FROM THE REGENERATE TRIAL OF OBETICHOLIC ACID FOR THE TREATMENT OF NONALCOHOLIC STEATOHEPATITIS (S403 - McCormick Place) - Mar 23, 2023 - Abstract #DDW2023DDW_3647;
In the ongoing REGENERATE trial, subjects receiving OCA 25 mg were twice as likely to experience ?1 stage improvement in liver fibrosis with no worsening of NASH at month 18 compared to subjects receiving placebo at 18 months using 2 different histologic methodologies. The confirmed antifibrotic effect in liver histology, together with extended exposure within the largest safety database in NASH to date, demonstrates that OCA 25 mg was generally safe and well tolerated, supporting the long-term use of OCA to treat pre-cirrhotic fibrosis due to NASH.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, ursodeoxycholic acid / Generic mfg.
Journal: Management of Primary Biliary Cholangitis: Current Treatment and Future Perspectives. (Pubmed Central) - Mar 3, 2023
However, evidence supporting the use of certain novel therapies over others is sparse. There is a need for additional clinical trials as well as research aimed at the underlying pathophysiology of primary biliary cholangitis to discover additional therapeutic targets.
- |||||||||| Entereg (alvimopan) / Merck (MSD), Ocaliva (obeticholic acid) / Intercept
FDA event, Journal: Repurposing FDA Approved Drugs as FXR Agonists: A Structure Based in silico Pharmacological Study. (Pubmed Central) - Mar 2, 2023
Our results showed that alvimopan and montelukast could be used as potent FXR activators and outperform the binding affinity of obeticholic acid by forming stable conformation with the protein in silico. However, further investigational studies and validations of the selected drugs are essential to figure out their suitability for in vivo experiments and clinical trials.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, Bezalip SR (bezafibrate) / AbbVie, Intercept, Miravo
Trial completion date, Trial primary completion date, Combination therapy: Study of OCA in Combination with BZF Evaluating Efficacy, Safety, and Tolerability in Participants with PBC (clinicaltrials.gov) - Feb 27, 2023
P2, N=75, Recruiting,
These preliminary findings reveal the crucial role of gut microbiota in Meth-induced anxiety-like behavior and neuroinflammation, highlighting OCA as a potential candidate for the prevention of Meth-induced anxiety. Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2023 --> Oct 2024
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Selected Aspects of the Intricate Background of Immune-Related Cholangiopathies-A Critical Overview. (Pubmed Central) - Feb 12, 2023
In this review, we highlight the role of key factors such as the gut-liver axis, intestinal barrier integrity, bile acid synthesis and circulation, and microbiome composition, which seem to be strongly related to PBC and PSC outcome. Emerging treatments and future therapeutic strategies are also presented.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Application of the Latest Advances in Evidence-Based Medicine in Primary Biliary Cholangitis. (Pubmed Central) - Feb 3, 2023
These include updates to prognostic models on risk stratification, new noninvasive tools for staging of disease, updates to the appropriate use of and long-term treatment results with obeticholic acid as a second-line treatment, the emerging therapeutic role of fibrates, and the advancement of investigational agents for managing PBC. In this updated expert consensus document, we provide updates on staging, the use of noninvasive prognostic tools, and a treatment algorithm to provide evidence-based and practical tools for clinicians who manage PBC, with the ultimate goal to improve the long-term outcomes for patients with this chronic liver disease.
- |||||||||| Review, Journal: PPAR agonists for the treatment of primary biliary cholangitis: Old and new tales. (Pubmed Central) - Jan 24, 2023
Ursodeoxycholic Acid (UDCA) is the standard of care treatment, Obeticholic Acid (OCA) has been approved as second-line therapy for those non responder or intolerant to UDCA...Bezafibrate, the most evaluated, is currently used in clinical practice in combination with UDCA in referral centers...Testing new therapeutic opportunities in PBC is challenging due to its low prevalence and slow progression. However, new drugs including PPAR agonists, are currently under investigation and should be considered for at-risk PBC patients.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Trial completion: Phase 2 Study of Obeticholic Acid for Lipodystrophy Patients (clinicaltrials.gov) - Jan 13, 2023
P2, N=13, Completed,
ALS-L1023 may exert anti-fibrotic effects in the NAFLD model, suggesting that it may provide potential benefits for the treatment of liver fibrosis. Active, not recruiting --> Completed
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal, IO biomarker: Obeticholic acid and 5β-cholanic acid 3 exhibit anti-tumor effects on liver cancer through CXCL16/CXCR6 pathway. (Pubmed Central) - Jan 7, 2023
In vivo experiments, we found that farnesoid X receptor agonist (obeticholic acid) combined with the takeda G protein coupled receptor 5 antagonist (5β-cholanic acid 3) exhibited significant tumor suppressive effects in the orthotopic liver tumor model and this result may be related to the CXCL16/CXCR6 axis. In conclusion, our study provides the basis and potential strategies for HCC immunotherapy based on NKT cells.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Preclinical, Journal: Microbiota-induced lipid peroxidation impairs obeticholic acid-mediated antifibrotic effect towards nonalcoholic steatohepatitis in mice. (Pubmed Central) - Jan 1, 2023
We further elucidate that OCA reduces triglycerides containing polyunsaturated fatty acid (PUFA-TGs) levels, whereas elevates free PUFAs and phosphatidylethanolamines containing PUFA (PUFA-PEs), which are susceptible to be oxidized to lipid peroxides (notably arachidonic acid (ARA)-derived 12-HHTrE), inducing hepatocyte ferroptosis and activating hepatic stellate cells (HSCs). Inhibiting lipid peroxidation with pentoxifylline (PTX) rescues anti-fibrotic effect of OCA, suggesting combination of OCA and lipid peroxidation inhibitor could be a potential antifibrotic pharmacological approach in clinical NASH-fibrosis.
- |||||||||| INT-767 / Intercept, Evkeeza (evinacumab-dgnb) / Regeneron, Ultragenyx
Journal: Kidney and lipids: novel potential therapeutic targets for dyslipidemia in kidney disease? (Pubmed Central) - Dec 23, 2022
Additionally, several promising agents, such as cyclodextrins and the FXR/TGR5 dual agonist, INT-767, can improve renal lipid metabolism disorders and delay CKD progression. Drugs targeting mitochondrial dysfunction could be an option for the treatment of dyslipidemia and lipotoxicity, particularly in renal diseases.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Trial completion date, Trial primary completion date, Real-world evidence, Real-world: HEROES PBC: A Real-World Data Study to Evaluate the Effectiveness of OCA on Hepatic Outcomes in PBC Patients (clinicaltrials.gov) - Dec 19, 2022
P=N/A, N=2350, Enrolling by invitation,
Drugs targeting mitochondrial dysfunction could be an option for the treatment of dyslipidemia and lipotoxicity, particularly in renal diseases. Trial completion date: Oct 2022 --> Jul 2023 | Trial primary completion date: Sep 2022 --> Jun 2023
- |||||||||| Update on clinical management of Primary Biliary Cirrhosis (3F Plenary Hall) - Dec 18, 2022 - Abstract #APASL2023APASL_237;
Novel PPAR agonists for PBC including elafibranor (PPAR-ad), saroglitazar (PPARa/g), and seladelpar(PPARd) showed a favorable biochemical response in phase 2 clinical trials. Lastly, RCT of linerixibat (an ileal bile acid transporter inhibitor) in PBC patients showed improvement in pruritus severity.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, lanifibranor (IVA337) / Inventiva
Pharmacotherapy: Past and Current (2F Room 201ABC) - Dec 18, 2022 - Abstract #APASL2023APASL_220;
Although there is currently no licensed treatment for metabolic dysfunction-associated fatty liver disease, guidelines support the use of vitamin E, pioglitazone or glucagon-like peptide-1 receptor agonists in selected patients with steatohepatitis...In the interim Week 72 histological assessment of the phase 3 REGERNATE study, obeticholic acid at a dose of 25 mg daily improved liver fibrosis with no worsening of steatohepatitis...Lanifibranor, a pan-PPAR agonist, was shown to both resolve steatohepatitis and improve fibrosis in a phase 2b study. Because the pathogenesis of steatohepatitis is complicated and heterogeneous, it is believed that precision medicine and combination treatments will be needed.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, cilofexor (GS-9674) / Gilead
Interference Between AILD and Other Major Liver Diseases (1F Room 102) - Dec 18, 2022 - Abstract #APASL2023APASL_150;
These compounds are very interesting because FXR is a key regulator for fat metabolism and FXR agonist is expected to be effective NAFLD/NASH as well. FXR agonists may dramatically alter the natural course of cholestatic liver disease, especially PSC, with or without NAFLD/NASH.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Global Trends of Rates and Outcomes of AILD: A 2023 Update (1F Room 102) - Dec 18, 2022 - Abstract #APASL2023APASL_102;
Advances have been made in PBC treatment because secondline treatments including obeticholic acid are now available...Liver transplant remains the best option for patients who develop decompensated cirrhosis or hepatocellular carcinoma within specific criteria, but recurrent AILD might occur. Continued efforts are warranted to develop global networks for AILD aimed at assessing geo-epidemiological and clinical differences to capture the new treatment era for AILD.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Current Therapy of Various AILD: A Viewpoint From the West (1F Room 102) - Dec 18, 2022 - Abstract #APASL2023APASL_77;
Rituximab can alternatively be considered when relapse has occurred (EASL CP Guidelines Sclerosing Cholangitis. J Hepatol 2022;77:761).
- |||||||||| bile acid cholic acid (INT-777) / Intercept
Preclinical, Journal: Secondary bile acid lithocholic acid attenuates neurally evoked ion transport in the rat distal colon. (Pubmed Central) - Dec 16, 2022
The bile acid receptor TGR5 agonist INT-777 mimicked the LCA-induced inhibitory action...These results suggest that LCA inhibits neurally evoked Cl/HCO secretion through the activation of TGR5 on L cells and cholinergic- and VIP-secretomotor neurons in the submucosal plexus. Furthermore, the inhibitory mechanism may involve TGR5-stimulated PYY release from L cells and Y2R activation in VIP-secretomotor neurons.
- |||||||||| bile acid cholic acid (INT-777) / Intercept
Journal: Identification of the Role of TGR5 in the Regulation of Leydig Cell Homeostasis. (Pubmed Central) - Dec 12, 2022
Here, we investigated the potential role of TGR5 within Leydig cells using cell culture approaches combined with pharmacological exposure to the TGR5 agonist INT-777...In conclusion, the present work highlights the impact of the TGR5 signaling pathway on testosterone production and reinforces the links between bile acid signaling pathways and the testicular endocrine function. The testicular bile acid pathways need to be further explored to increase our knowledge of pathologies associated with impaired testicular endocrine function, such as fertility disorders.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Preclinical, Journal: Obeticholic acid treatment ameliorates the cardiac dysfunction in NASH mice. (Pubmed Central) - Dec 10, 2022
The testicular bile acid pathways need to be further explored to increase our knowledge of pathologies associated with impaired testicular endocrine function, such as fertility disorders. Chronic FXR activation with OCA is a potential strategy for activating IL-10/IL-10R signalling, reversing cardiac regulatory T cell dysfunction, and improving inflammasome-mediated NASH-related cardiac dysfunction.
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