- |||||||||| Ocaliva (obeticholic acid) / Intercept
Preclinical, Journal: Oxidation of fish oil exacerbates alcoholic liver disease by enhancing intestinal dysbiosis in mice. (Pubmed Central) - Jun 22, 2021 Stabilization of intestinal barrier by obeticholic acid markedly blunted OFO-aggravated liver injury in alcohol-fed mice. These results demonstrate that OFO exacerbates alcoholic liver injury through enhancing intestinal dysbiosis, barrier dysfunction, and hepatic inflammation mediated by gut-derived endotoxin.
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Trial completion date, Trial primary completion date: Phase 2 Study of Obeticholic Acid for Lipodystrophy Patients (clinicaltrials.gov) - Jun 4, 2021 P2, N=20, Recruiting, On the basis of these results, it may be concluded that the strategy of combining OCA with SIM represents an effective pharmacotherapy for NASH. Trial completion date: Jun 2021 --> Jan 2022 | Trial primary completion date: May 2021 --> Dec 2021
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Clinical, Journal: Impact of Obeticholic Acid on the Lipoprotein Profile in Patients with Nonalcoholic Steatohepatitis. (Pubmed Central) - Jun 2, 2021 P2 Recently, obeticholic acid (OCA), a farnesoid X receptor agonist, improved liver disease but led to an increase in cholesterol, however, the impact of OCA on cholesterol is not well understood. In the present study, we present data showing that OCA therapy is associated with an increase in lipoprotein levels which improve after drug discontinuation.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, resmetirom (MGL-3196) / Madrigal
Clinical, P3 data: 5/non-invasive liver testing, @Nordic_Bio @novonordisk #obeticholicacid, Phase3, Semaglutide, #TrialDesign, #resmetirom, primary endpoints, clinical development strategy, (Twitter) - May 28, 2021
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Review, Journal: Novel insights into the organic solute transporter alpha/beta, OSTα/β: From the bench to the bedside. (Pubmed Central) - May 28, 2021 Obeticholic acid, a semi-synthetic bile acid used to treat PBC, under review for the treatment of NASH, and in development for the treatment of other metabolic disorders, induces OSTα/β...This review article has been compiled to comprehensively summarize the recent data emerging on OSTα/β, recapitulating the available literature on the structure-function and expression-function relationships of OSTα/β, the regulation of this important transporter, the interaction of drugs and other compounds with OSTα/β, and the comparison of OSTα/β with other solute carrier transporters as well as adenosine triphosphate-binding cassette transporters. Findings from basic to more clinically focused research efforts are described and discussed.
- |||||||||| JQ-1 / Roche, Ocaliva (obeticholic acid) / Intercept
Clinical, Journal: BRD4 inhibition and FXR activation, individually beneficial in cholestasis, are antagonistic in combination. (Pubmed Central) - May 25, 2021 While BRD4 promotes hepatic inflammation and fibrosis in cholestasis, paradoxically, BRD4 is required for the anti-inflammatory, anti-fibrotic actions of OCA-activated FXR. Co-treatment with OCA and JQ1, individually beneficial, may be antagonistic in treatment of liver disease patients with inflammation and fibrosis complications.
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Biomarker, Journal: Obeticholic Acid Derivative, T-2054 Suppresses Osteoarthritis via Inhibiting NF-κB-Signaling Pathway. (Pubmed Central) - May 21, 2021 In summary, we showed for the first time that T-2054 effectively reduced the release of inflammatory mediators, as well as promoted extracellular matrix (ECM) synthesis via the NF-κB-signaling pathway. Our findings support the potential use of T-2054 as an effective therapeutic agent for the treatment of OA.
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Review, Journal: Farnesoid X receptor (FXR): Structures and ligands. (Pubmed Central) - May 20, 2021 With the approval of obeticholic acid (OCA) as the first small molecule to target FXR, many other small molecules are being evaluated in clinical trials. This review summarizes the structures of FXR, especially its ligand binding domain, and the development of small molecules (including agonists and antagonists) targeting FXR.
- |||||||||| cenicriviroc (TBR-652) / Takeda, AbbVie, Ocaliva (obeticholic acid) / Intercept
Review, Journal: Non-alcoholic fatty liver diseases: current challenges and future directions. (Pubmed Central) - May 15, 2021 However, up to now the prevention of overweight and lack of exercise targets the most important risk factors. This review aims to identify therapy relevant risk factors, management strategies, and open questions concerning NAFLD patients.
- |||||||||| Review, Journal: Non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH)-related liver fibrosis: mechanisms, treatment and prevention. (Pubmed Central) - May 15, 2021
While several promising drug candidates failed in phase 2 or 3 clinical trials (including elafibranor, emricasan and selonsertib), promising results with the farnesoid X receptor agonist obeticholic acid, the pan-PPAR agonist lanifibranor and the chemokine receptor CCR2/CCR5 inhibitor cenicriviroc support the expectation of an effective pharmacological therapy for liver fibrosis in the near future. Tackling NAFLD-associated fibrosis from different directions by combinatorial drug treatment and effective lifestyle changes hold the greatest prospects.
- |||||||||| 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) - May 6, 2021 P2, N=72, Recruiting, Trial completion date: Oct 2022 --> Sep 2025 | Trial primary completion date: Oct 2022 --> Sep 2025 Trial completion date: Feb 2023 --> Jun 2023 | Trial primary completion date: Mar 2022 --> Jul 2022
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Review, Journal: Emerging New Diagnostic Modalities and Therapies of Nonalcoholic Fatty Liver Disease. (Pubmed Central) - May 4, 2021 As we continue to await the first FDA-approved therapeutic agent for NASH, lifestyle change remains the main modality of treatment. Newer diagnostic and treatment modalities for pediatric NAFLD continue to be in development under FDA guidance.
- |||||||||| tropifexor (LJN452) / Novartis, Ocaliva (obeticholic acid) / Intercept
Journal: Structure-guided modification of isoxazole-type FXR agonists: Identification of a potent and orally bioavailable FXR modulator. (Pubmed Central) - May 4, 2021 Although the steroidal obeticholic acid, a full FXR agonist, was recently approved, several side effects probably due to insufficient pharmacological selectivity impede its further clinical application...Our efforts focusing on isoxazole-type FXR agonists, common nonsteroidal agonists for FXR, led to the discovery a series of novel FXR agonists bearing aryl urea moieties through structural simplification of LJN452 (phase 2)...Extensive in vitro evaluation further confirmed partial efficacy of 11k in cellular FXR-dependent gene modulation, and revealed its lipid-reducing activity. More importantly, orally administration of 11k in mice exhibited desirable pharmacokinetic characters resulting in promising in vivo FXR agonistic activity.
- |||||||||| Journal: New drugs for non-alcoholic steatohepatitis and HIV infection: great expectations with a great absent? (Pubmed Central) - Apr 21, 2021
The risk of DDI between ART and aramchol, cenicriviroc, elafibranor, obeticholic acid and resmetirom (MGL-3196), which are currently in phase III trials for the treatment of NASH, are reviewed. Finally, a model for trial design to include PLWH is proposed, strongly advocating for the scientific community to include this group as a sub-population within studies.
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Clinical, Journal: Liver Injury in Patients with Cholestatic Liver Disease Treated with Obeticholic Acid. (Pubmed Central) - Apr 15, 2021 Drug-induced liver injury (DILI) in patients with PBC can put them at risk for acute on chronic liver failure (ACLF) and increased mortality. We describe in this report worsening of liver disease or ACLF after starting OCA among a cohort of patients with PBC and primary sclerosing cholangitis (PSC).
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Journal: Obeticholic acid for the treatment of nonalcoholic steatohepatitis. (Pubmed Central) - Apr 14, 2021 The side effect of an atherogenic lipoprotein profile may adversely affect long-term outcomes, though studies have shown that co-administration of statins are able to mitigate this effect. OCA is likely to become an option for treatment but the specific context within which it may be prescribed stills need to be clarified.
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[VIRTUAL] Combining non-selective beta blockers with FXR agonists towards ameliorating intestinal barrier dysfunction in NASH (Poster area) - Apr 9, 2021 - Abstract #EASLILC2021EASL_ILC_889; The present study aimed at investigating the effect of combining carvedilol (CAR), a NSBB, to obeticholic acid (OCA), an FXR agonist on BTand, therefore, NASH histopathological features. Combining the NSBB, carvedilol, to OCA, decreased BT and mitigated the intestinal barrier dysfunction alongside NASH histopathological features in a combinedmodel of chronic colitis and dietary NASH suggesting its potential use in NASH patients with disrupted intestinal homeostasis.
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