- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Primary biliary cholangitis. (Pubmed Central) - Sep 15, 2024
Promising clinical investigations are underway to alleviate these symptoms. Efforts to facilitate better access to medical care and dissemination of current knowledge should enable diagnosis at an earlier stage of primary biliary cholangitis and ensure access to treatments based on risk stratification for all patients.
- |||||||||| Review, Journal: Managing bile acid diarrhea: aspects of contention. (Pubmed Central) - Sep 12, 2024
They are relatively inexpensive, and better-quality data is now available for colesevelam...The GLP-1 receptor agonist, liraglutide, is also effective, although mechanisms of action and whether this effect is common to other class members is unclear...The role of dietary factors in symptom development is a major patient concern, needing more formal studies. To build on recent findings, bile acid diarrhea needs further investment into causes, diagnosis and therapy to guide present and future patient care.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Triple Overlap: A Rare Case of PSC, PBC, and AIH in a Patient With Refractory Liver Disease (Exhibit Hall E) - Aug 20, 2024 - Abstract #ACG2024ACG_5366;
She did not respond over 3 years to prednisone, cellcept, azathioprine, tacrolimus, ursodiol, ocaliva, sirolimus...Last visit in clinic, she complained of severe pruritus and was tried with different medications but did not respond to maximum dose of cholestyramine, Atarax, Benadryl, emollients, SSRI...Novel therapies needs to be investigated and explored for such patients with refractory overlap syndromes. We chose to send patient for liver transplant evaluation.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Statins Protect Against Major Liver Events in Patients With Primary Biliary Cholangitis (Exhibit Hall E) - Aug 20, 2024 - Abstract #ACG2024ACG_5129;
160 patients with PBC were identified, with a total of 24 liver events (Table 1). Patients with major liver events at baseline more frequently were cirrhotic (p = 0.05), had higher alkaline phosphatase (p 90%) and obeticholic acid (~10%) were similar between groups.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Stabilization of Enhanced Liver Fibrosis and Liver Stiffness Measures in the Open-Label Extension of the Phase 3 POISE Trial of Obeticholic Acid for the Treatment of Primary Biliary Cholangitis (Exhibit Hall E) - Aug 20, 2024 - Abstract #ACG2024ACG_3991;
The mean ELF scores were 9 at BL, 9.19 at M12, and 9.31 at M24 in pts with moderate fibrosis. In pts with severe fibrosis, mean ELF scores were 10.35 at BL, 10.36 at M12, and 10.56 at M24, and for cirrhosis, mean ELF scores were 11.92 at BL, 11.54 at M12, and 11.35 at M24.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Evaluation of Aspartate Aminotransferase to Platelet Ratio Index and Fibrosis-4 Index Stabilization in the Phase 3 POISE Trial of Obeticholic Acid for the Treatment of Primary Biliary Cholangitis (Exhibit Hall E) - Aug 20, 2024 - Abstract #ACG2024ACG_3990;
In pts with severe fibrosis, mean ELF scores were 10.35 at BL, 10.36 at M12, and 10.56 at M24, and for cirrhosis, mean ELF scores were 11.92 at BL, 11.54 at M12, and 11.35 at M24. In the DB phase, mean APRI scores increased in PBO-pts with low or high APRI at BL (0.37 at BL vs 0.38 at M12 and 2.76 at BL vs 3.37 at M12, respectively) but decreased in OCA 5
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Obeticholic Acid Normalizes Inflammatory Biomarkers in Patients With Primary Biliary Cholangitis (Exhibit Hall E) - Aug 20, 2024 - Abstract #ACG2024ACG_3949;
In the full intent-to-treat population, median BL levels of TNF? were 11.7, 10.1, and 10.8 pg/mL for PBO, OCA titration, and OCA 10 mg, respectively, and median change from BL at month 12 was 1.2, 0.8, and -0.2 pg/mL (p 8.1 pg/mL at BL (79%), 3% (2/58) on PBO, 23% (10/43) on OCA titration, and 14% (7/49) on OCA 10 mg normalized at month 12 (p < 0.05 for both vs PBO).
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Preclinical, Journal: Effect of compound treatments on mouse lens viscoelasticity. (Pubmed Central) - Aug 18, 2024
This study aimed to evaluate the effects of 25-hydroxycholesterol, lipoic acid, and obeticholic acid on the viscoelastic properties of mouse lenses using a custom-built elastometer system...In conclusion, older mouse lenses are stiffer and less viscous than young mouse lenses. Notably, no significant change in lens stiffness was observed following treatment with lipoic acid, contrary to previous findings.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Edaravone and obeticholic acid protect against cisplatin-induced heart toxicity by suppressing oxidative stress and inflammation and modulating Nrf2, TLR4/p38MAPK, and JAK1/STAT3/NF-?B signals. (Pubmed Central) - Aug 17, 2024
Notably, rats co-administered with EDV plus OCA showed noticeable protection that exceeded that of EDV and OCA alone. In conclusion, our study provided that EDV, OCA, and their combinations effectively attenuated CIS-induced cardiac intoxication by activating Nrf2, PPAR?, and SIRT1 signals and downregulating NF-?B, JAK1/STAT3, and TLR4/p38MAPK signals.
- |||||||||| Iqirvo (elafibranor) / Ipsen, Ocaliva (obeticholic acid) / Intercept
Review, Journal: PPAR-Mediated Bile Acid Glucuronidation: Therapeutic Targets for the Treatment of Cholestatic Liver Diseases. (Pubmed Central) - Aug 9, 2024
Additionally, newer PPAR agonists that target various PPAR isoforms (?/?, ?) are under development as an adjunct therapy for PBC or PSC, although their impact on glucuronidation pathways are less characterized. This review will focus on PPAR-mediated bile acid glucuronidation as a therapeutic pathway to improve outcomes for patients with PBC and PSC.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: The treatment of primary biliary cholangitis: from shadow to light. (Pubmed Central) - Jul 31, 2024
Clinical research is focusing on several other groups of drugs: peroxisome proliferator-activated receptor (PPAR) ?- and ?/? agonists, non-steroidal farnesoid X receptor agonists, fibroblast growth factor 19 modulators, and inhibitors of nicotinamide adenine dinucleotide phosphate oxidase 1 and 4.
- |||||||||| Journal: Immunological mechanisms in steatotic liver diseases: An overview and clinical perspectives. (Pubmed Central) - Jul 11, 2024
Immunological modulations targeting hepatocyte death, inflammatory reactions and gut microbiome include N-acetylcysteine, selonsertib, F-652, prednisone, pentoxifylline, anakinra, JKB-121, HA35, obeticholic acid, probiotics, prebiotics, antibiotics and FMT. Understanding the immunological mechanisms underlying in SLD is crucial for advancing clinical therapeutic strategies.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Progress in the Management of Patients with Cholestatic Liver Disease: Where Are We and Where Are We Going? (Pubmed Central) - Jul 8, 2024
Considerable progress has been made in the management of cholestatic liver disease but there are still many opportunities and challenges. In this review, we summarized the recommended guidelines for the management of cholestatic disease and the progress of new drug research and development, in order to provide an important reference for the clinical practice of cholestatic liver disease.
- |||||||||| bile acid cholic acid (INT-777) / Intercept
Preclinical, Journal: Bile acids differentially regulate longitudinal smooth muscle contractility in everted mouse ileum. (Pubmed Central) - Jul 8, 2024
These results demonstrate that gentle eversion of intact mouse ileum facilitates the quantification of longitudinal smooth muscle contractile responses to individual bile acids. Prokinetic effects of ursodeoxycholic acid and low-dose deoxycholic acid are replicated by agonists to TGR5 and muscarinic acetylcholine receptors.
- |||||||||| 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) - Jul 3, 2024
P2, N=60, Active, not recruiting,
Prokinetic effects of ursodeoxycholic acid and low-dose deoxycholic acid are replicated by agonists to TGR5 and muscarinic acetylcholine receptors. Trial completion date: Aug 2024 --> Feb 2025 | Trial primary completion date: Aug 2024 --> Nov 2024
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Microbiota metabolized Bile Acids accelerate Gastroesophageal Adenocarcinoma via FXR inhibition. (Pubmed Central) - Jun 25, 2024
Treatment of murine organoids and L2-IL1B mice with the FXR agonist obeticholic acid (OCA) deacelerated GEAC progression...Further, FXR activation protected with OCA ameliorated the phenotype in vitro and in vivo, suggesting that FXR agonists have potential as differentiation therapy in GEAC prevention. If its inhibition is linked to disease progression and its activation to cancer prevention, exploring the potential of FXR as a therapeutic target has great clinical relevance in GEAC context.
- |||||||||| tropifexor (LJN452) / Novartis, Ocaliva (obeticholic acid) / Intercept, cilofexor (GS-9674) / Gilead
Review, Journal: Investigational farnesoid X receptor agonists for the treatment of primary biliary cholangitis. (Pubmed Central) - Jun 23, 2024
Close to half of such patients show a remarkable improvement when additionally treated with Obeticholic acid (OCA) but have a dose-dependent increase of pruritus...However, as with OCA, pruritus remains a concern with the newer drugs despite targeted chemical modifications to increase FXR specificity. Directing future resources toward studying the molecular mechanisms behind pruritus may lead to better drug design and efficacious yet safer drugs.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Emerging drugs for the treatment of hepatic fibrosis on nonalcoholic steatohepatitis. (Pubmed Central) - Jun 21, 2024
modulator have been reported to be effective against fibrosis, although further evidence is required. The effects of pan-peroxisome proliferator-activated receptors, obeticholic acid, and fibroblast growth factor-21 analogs on liver fibrosis in the development stage therapeutics for NASH are of particular interest.
- |||||||||| Trulicity (dulaglutide) / Eli Lilly, bile acid cholic acid (INT-777) / Intercept
Preclinical, Journal: Lactobacillus reuteri JCM 1112 ameliorates chronic acrylamide-induced glucose metabolism disorder via the bile acid-TGR5-GLP-1 axis and modulates intestinal oxidative stress in mice. (Pubmed Central) - Jun 17, 2024
Here, C57BL/6N mice were orally administered with 5 mg per kg bw AA for 10 weeks, followed by another 3 weeks of glucagon-like peptide-1 (GLP-1) analogue (dulaglutide) treatment...Then, mice were administered with AA or AA + INT-777 (Takeda G-protein-coupled receptor 5 (TGR5) agonist) for 10 weeks...In addition, L. reuteri significantly enhanced ileal superoxide dismutase and catalase activities and total antioxidant capacity, thereby preventing chronic AA-induced oxidative stress. Our research provides new insights into the GMD toxicity of chronic low-dose AA and confirms the role of probiotics in alleviating AA-induced GMD.
- |||||||||| ursodeoxycholic acid / Generic mfg.
Review, Journal: Treatment in primary biliary cholangitis: Beyond ursodeoxycholic acid. (Pubmed Central) - Jun 5, 2024
Randomized controlled trials showed improvements in the key biochemical surrogate markers with the addition of these drugs, which have also been associated with improved clinical outcome. Considering this evolving PBC landscape, with more versatile treatment options and treatment goals, this review recapitulates the recent insight in UDCA therapy, the selection of patients with a residual risk of liver disease progression and the results of the currently available second line treatment options.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, liproxstatin-1 / Jilin University
Journal: A combined nanotherapeutic approach targeting farnesoid X receptor, ferroptosis, and fibrosis for nonalcoholic steatohepatitis treatment. (Pubmed Central) - May 27, 2024
Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist with favorable effects on fatty and glucose metabolism, has been considered the leading candidate drug for nonalcoholic steatohepatitis (NASH) treatment...ONL@MSN also displayed enhanced therapeutic actions on the maintenance of intrahepatic macrophages/monocytes homeostasis, inhibition of immune response/lipid peroxidation, and correction of microbiota dysbiosis. These findings present a promising synergistic nanotherapeutic strategy for the treatment of NASH by simultaneously targeting FXR, ferroptosis, and fibrosis.
- |||||||||| bile acid cholic acid (INT-777) / Intercept
Biased GPBAR Signaling in Regulating Islet Homeostasis and Glucose Metabolism (Poster Hall (West A4-B2); 1758) - May 20, 2024 - Abstract #ADA2024ADA_2704;
Decompensation was linked to pre-existing portal hypertension. These findings collectively indicated that ligands of GPBAR with Gs-biased viability, may could better improve islet homeostasis and provide a rational design of GPBAR-targeting drugs for diabetes or other metabolic diseases.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Real-world study of reasons for non-utilization of second-line treatment in patients with primary biliary cholangitis (Track Hub: Immune-mediated & Cholestatic Diseases) - May 14, 2024 - Abstract #EASLILC2024EASL_ILC_2817;
This study revealed that only about one-quarter of patients who met eligibility criteria for initiating a 2L treatment received an approved 2L treatment. The findings of this study underscore that there remains unmet need in the 2L treatment space and that current 2L treatment options may not fully address patients' and healthcare providers' needs.
|
