- |||||||||| Iqirvo (elafibranor) / Ipsen, Ocaliva (obeticholic acid) / Intercept, Livdelzi (seladelpar) / Gilead
Journal: Primary Biliary Cholangitis: personalizing second-line therapies. (Pubmed Central) - Dec 21, 2024 They also have shown biochemical improvements among patients with an inadequate response to ursodeoxycholic acid but may improve symptoms of pruritus. Herein, we review the patient features to consider when deciding whether a second-line agent is indicated and which agent to consider for a truly personalized approach to PBC patient care.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Enhanced dynamic coupling in a nuclear receptor underlies ligand activity. (Pubmed Central) - Dec 16, 2024 We combined functional assays with over 200 microseconds of simulations, revealing an unexpected role for helix 5 in the allosteric signaling of obeticholic acid (OCA)...Ultimately, the enhanced potency of the bile acid analog can be traced to its effect on FXR dynamics. In addition to identifying a previously unknown mechanistic role for helix 5-helix 7 coupling in FXR, these results emphasize the inextricable linkage between the activity of nuclear receptor ligands and their effects on receptor dynamics.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal, Real-world evidence, Real-world: Hepatic real-world outcomes with obeticholic acid in primary biliary cholangitis (HEROES): A trial emulation study design. (Pubmed Central) - Dec 4, 2024 P=N/A In addition to identifying a previously unknown mechanistic role for helix 5-helix 7 coupling in FXR, these results emphasize the inextricable linkage between the activity of nuclear receptor ligands and their effects on receptor dynamics. We identified a 63% reduced risk of hospitalization for hepatic decompensation, liver transplant, or death in OCA-treated versus non-OCA-treated individuals.
- |||||||||| fuzheng Huayu / Shanghai Sundise
Preclinical, Journal: Study on the mechanism of Fuzheng Huayu formula against biliary fibrosis in mice (Pubmed Central) - Nov 28, 2024 in liver tissues of FZHY mice was significantly increased (P<0.05), and the NF-?B phosphorylation was significantly inhibited compared with Mdr2-/- mice (P<0.05). FZHY significantly ameliorated liver fibrosis, ductular reaction and inflammation in Mdr2-/- spontaneous biliary fibrosis mice, and its mechanism was related to the regulation of PPAR?/NF-?B pathway.
- |||||||||| INT-767 / Intercept
Journal: Aberrant basement membrane production by HSCs in MASLD is attenuated by the bile acid analog INT-767. (Pubmed Central) - Nov 25, 2024 These findings highlight the importance of basement membrane remodeling in MASH pathobiology and as a source of circulating biomarkers. Basement membrane deposition by activated HSCs is abrogated by INT-767 treatment and measurement of basement membrane molecules should be included when determining the therapeutic efficacy of FXR agonists.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: An efficient regioconvergent synthesis of 3-aza-obeticholic acid. (Pubmed Central) - Nov 21, 2024 Upon individual N-Boc-protection, these underwent annulation to the 3-aza-A-ring when subjected to either mesylation or a Dess-Martin oxidation/hydrogenation sequence. Global deprotection of the 3-aza-intermediate delivered 3-aza-OCA in ten steps and an overall yield of up to 19?%.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Sub-optimal therapy of patients with primary biliary cholangitis (PBC) in the real-life stetting of the German PBC cohort. (Pubmed Central) - Nov 13, 2024 OCA (13% vs. 4.5%) and BZF (14% vs. 6.5%) were significantly more often prescribed by academic vs. nonacademic centres.Pruritus (27% vs. 15.5%), fatigue (23% vs. 4.5%), and sicca syndrome (14% vs. 1%) were significantly more often reported by academic centres.The German PBC registry could be established, which indicates suboptimal therapy in a relevant proportion of patients and shows significant differences between academic and nonacademic centres. Results are fundamental to improving clinical management at different levels of care.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Obeticholic acid's effect on HDL function in MASH varies by diabetic status. (Pubmed Central) - Nov 13, 2024 In all patients, serum glucose levels were negatively correlated with OCA-induced change in pro-inflammatory function in HDL (p?<?0.001), which was primarily due to diabetes (p?=?0.05). These preliminary results suggest a distinct effect of OCA therapy on diabetic and nondiabetic patients with MASH and warrant a future large-scale study.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Primary Biliary Cholangitis and Primary Sclerosing Cholangitis Therapy Landscape. (Pubmed Central) - Oct 31, 2024 While significant progress has been made in development of therapies for PBC, there are no current approved treatments for PSC other than liver transplantation although several emerging therapies have shown encouraging results. This review outlines the current and upcoming treatments for PBC and PSC.
- |||||||||| bile acid cholic acid (INT-777) / Intercept
Journal: Activation of TGR5 in the injured nerve site according to a prevention protocol mitigates partial sciatic nerve ligation-induced neuropathic pain by alleviating neuroinflammation. (Pubmed Central) - Oct 25, 2024 Perisciatic nerve administration of the TGR5 agonist, INT-777 according to a prevention protocol (50 ?g/?L daily from postoperative day [POD] 0 to POD6) provided sustained relief from mechanical allodynia and spontaneous pain, whereas the TGR5 antagonist, SBI-115 worsened neuropathic pain...Furthermore, the activation of microglia in the spinal cord on POD7 and POD14 was altered when TGR5 in the sciatic nerve was manipulated. Collectively, TGR5 activation in the injured nerve site mitigates neuropathic pain by reducing neuroinflammation, while TGR5 knockdown in myeloid cells worsens pain by enhancing neuroinflammation.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, Bezalip SR (bezafibrate) / AbbVie, Intercept, Miravo
PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTION OF OBETICHOLIC ACID AND BEZAFIBRATE IN HEALTHY VOLUNTEERS () - Oct 15, 2024 - Abstract #AASLD2024AASLD_3119; BZF increased total OCA plasma levels with high variability, while OCA had a slight effect on BZF levels. Together, they reduced C4 to a larger extent than either alone at a low dose of OCA, suggesting potential incremental benefit of their combination on reducing BA synthesis compared with OCA alone.
- |||||||||| Iqirvo (elafibranor) / Ipsen
ONE-YEAR TREATMENT WITH ELAFIBRANOR IN THE PHASE III ELATIVE () - Oct 15, 2024 - Abstract #AASLD2024AASLD_3057; P3 Considering the dose-dependent relation between UDCA and improved survival, optimizing first-line therapy may result in additional life-years. In the phase III ELATIVE
- |||||||||| Ocaliva (obeticholic acid) / Intercept
OBETICHOLIC ACID FOR PRIMARY BILIARY CHOLANGITIS IN THE PREVENTION OF CLINICAL EVENTS: A MODELING STUDY USING REAL-WORLD DATA () - Oct 15, 2024 - Abstract #AASLD2024AASLD_3041; Although clinical trials in PBC provide an important measure of effectiveness based on liver biochemistries, studies in RW settings have demonstrated the benefit of OCA on long-term outcomes, as the medication has been used in regular clinical practice since its accelerated approval in 2016. Using RW data to estimate clinical events avoided demonstrates the long-term clinical benefit of OCA for appropriate patients with PBC.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
TREATMENT RESPONSE IN PRIMARY BILIARY CHOLANGITIS BASED ON DIFFERING CRITERIA () - Oct 15, 2024 - Abstract #AASLD2024AASLD_3034; Criteria for UDCA response should identify the need for second line therapy. Conservative criteria of achieving normal ALP and subnormal Tbili may be the optimal endpoint, however in our group only 36% of patients achieved this and providers did not add second line therapy in the majority of this group.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
FIBRATE-OCA (FI-OCA) STUDY - A GLOBAL SNAPSHOT OF PBC PRACTICE AROUND THE GLOBE () - Oct 15, 2024 - Abstract #AASLD2024AASLD_1432; Background: The introduction of obeticholic acid (OCA) and the emerging evidence on the efficacy of fibrates and other PPAR-agonists have changed the treatment paradigm for primary biliary cholangitis (PBC) and increased the complexity of disease management, resulting in heterogeneous and diverse PBC practices worldwide...Among these, 635 patients started on bezafibrate and 233 on fenofibrate... Management of PBC demands dynamic adjustments to second-line treatments, and high discontinuation and change rates underscore the urgent need for better allocation tools.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, Rezdiffra (resmetirom) / Madrigal Pharma
A NEW THERAPEUTIC APPROACH FOR MASLD/MASH TREATMENT () - Oct 15, 2024 - Abstract #AASLD2024AASLD_721; Therefore, NTP can be a useful intervention for treating MASLD/MASH. Widely used for over 50 years in Japan and China without significant side effect, NTP can be an effective and safe medication for MASLD/MASH management.
- |||||||||| Review, Journal: Bile Acids-Based Therapies for Primary Sclerosing Cholangitis: Current Landscape and Future Developments. (Pubmed Central) - Oct 15, 2024
The ursodeoxycholic acid (UDCA) has been widely used, although there is no evidence that the use of UDCA delays the time to liver transplant or increases survival...The largest group of these new agents is represented by FXR agonists, including obeticholic acid, cilofexor, and tropifexor...Additional agents under evaluation are PPARs (elafibranor and seladelpar), anti-itching agents such as MAS-related G-protein-coupled receptors antagonists, and anti-fibrotic and immunosuppressive agents. Drugs targeting gut bacteria and bile acid pathways are also under investigation, given the strong link between PSC and gut microbiota.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, lanifibranor (IVA337) / Inventiva, Hepalys Pharma
Review, Journal: Emerging Therapies for Non-Alcoholic Steatohepatitis (NASH): A Comprehensive Review of Pharmacological and Non-Pharmacological Approaches. (Pubmed Central) - Oct 14, 2024 The evolving landscape of NASH research emphasizes the need for multidisciplinary approaches integrating advances in diagnostics, therapeutics, and digital health technologies. As the field progresses, the focus remains on developing more effective, personalized, and accessible strategies for preventing, diagnosing, and treating NASH, with the ultimate goal of improving outcomes for patients affected by this increasingly prevalent liver disease.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Revisiting PPAR agonists: novel perspectives in the treatment of primary biliary cholangitis. (Pubmed Central) - Oct 11, 2024 Although obeticholic acid (OCA) is approved as a second-line therapy, it is not well-tolerated by patients with significant itching or advanced cirrhosis...Combining PPAR agonists with other treatments and advancing personalized approaches may enhance therapeutic efficacy and patient outcomes. This study provides future perspectives on the roles of PPAR agonists in PBC management.
- |||||||||| Iqirvo (elafibranor) / Ipsen, Ocaliva (obeticholic acid) / Intercept, Livdelzi (seladelpar) / Gilead
Review, Journal: Current Landscape and Evolving Therapies for Primary Biliary Cholangitis. (Pubmed Central) - Sep 27, 2024 In this review, we will examine published and ongoing clinical trials in PBC, including the recently approved peroxisome-proliferator-activated receptor (PPAR) agonist, elafibranor and seladelpar. These novel second-line therapies are expected to improve therapy in PBC and the development of personalized approaches.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Enrollment open, Trial initiation date: Study to Assess Efficacy, Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Obeticholic Acid (OCA) Compared to Placebo in Pediatric Participants With Biliary Atresia, Post-hepatoportoenterostomy (clinicaltrials.gov) - Sep 19, 2024 P2/3, N=144, Recruiting, These results illuminate the synergistic benefits of integrating an ROS-responsive biomimetic platform with OCA, offering a promising therapeutic avenue for PSC. Not yet recruiting --> Recruiting | Initiation date: Mar 2024 --> Sep 2024
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