- |||||||||| elafibranor (GFT505) / Genfit, Ocaliva (obeticholic acid) / Intercept
Journal: Human Multilineage 3D Spheroids as a Model of Liver Steatosis and Fibrosis. (Pubmed Central) - Jul 31, 2019
...Finally, this accumulation was rescued by incubating spheroids with liraglutide or elafibranor, drugs that are in clinical trials for the treatment of NASH...This tool may be used to understand molecular mechanisms involved in the early stages of fibrogenesis induced by lipid accumulation. Moreover, it may be used to identify new compounds to treat NASH using high-throughput drug screening.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Cholestatic and Autoimmune Liver Diseases SIG (Hynes Convention Center, Room 312) - Jul 26, 2019 - Abstract #AASLD2019AASLD_282;
Moreover, it may be used to identify new compounds to treat NASH using high-throughput drug screening. Recent approval of the synthetic FXR agonist obeticholic acid for primary biliary cholangitis treatment shows that targeting nuclear receptors in treating liver diseases, particularly cholestatic and autoimmune conditions, has therapeutic potential. At this symposium, translational researchers and clinical investigators with expertise in cholestatic diseases will review recent preclinical and clinical studies and Discuss rapidly emerging novel and efficient therapies.Learning Objectives: Discuss the most recent progresses on bile acid signaling in cholestatic liver diseases Review clinical practice approaches based on the most recent preclinical and clinical investigations
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Current and Promising Therapy for Primary Biliary Cholangitis. (Pubmed Central) - Jul 26, 2019
...Approved treatment options include ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) but novel therapies are being investigated...Several tools such as the Mayo Risk Score and GLOBE are available for prognostic modeling. Ultimately, patients with PBC may end up requiring liver transplantation and referral to a transplant center may also be needed.
- |||||||||| INT-767 / Intercept, Ocaliva (obeticholic acid) / Intercept, bile acid cholic acid (INT-777) / Intercept
Journal: FXR/TGR5 Dual Agonist Prevents Progression of Nephropathy in Diabetes and Obesity. (Pubmed Central) - Jul 17, 2019
Additionally, in mice with diet-induced obesity, INT-767 prevented mitochondrial dysfunction and oxidative stress determined by fluorescence lifetime imaging of NADH and kidney fibrosis determined by second harmonic imaging microscopy. These results identify the renal signaling pathways regulated by FXR and TGR5, which may be promising targets for the treatment of nephropathy in diabetes and obesity.
- |||||||||| Journal: An update on the recent advances in antifibrotic therapy. (Pubmed Central) - Jul 17, 2019
Expert commentary: The tremendous advances in translational and clinical research fuels the hope for efficacious antifibrotic therapies within the next 5 years. Very likely, a combination of etiology-specific, metabolic, anti-inflammatory and direct anti-fibrotic interventions will be most effective.
- |||||||||| 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) - Jul 16, 2019
P=N/A, N=45, Recruiting,
Very likely, a combination of etiology-specific, metabolic, anti-inflammatory and direct anti-fibrotic interventions will be most effective. Trial completion date: Jul 2019 --> Dec 2019 | Trial primary completion date: Jun 2019 --> Dec 2019
- |||||||||| elafibranor (GFT505) / Genfit, Ocaliva (obeticholic acid) / Intercept, NGM282 / NGM Biopharmaceuticals
Journal: Nonalcoholic steatohepatitis, obesity, and cardiac dysfunction. (Pubmed Central) - Jul 13, 2019
Patients with NAFLD have a significant increase in cardiovascular disease risk. For biopsy-proven NASH, vitamin E and pioglitazone are the recommended medical treatments in addition to lifestyle modification.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Guideline review: British Society of Gastroenterology/UK-PBC Primary Biliary Cholangitis treatment and management guidelines. (Pubmed Central) - Jul 10, 2019
New guidelines have been produced for the management of primary biliary cholangitis, an infrequent but nonetheless important autoimmune liver disease. We provide a succient commentary and overview of the key features of disease management that arise from these recent guideline recommendations, with a focus on therapy with licensed agents (ursodeoxycholic acid and obeticholic acid) as well as personalised management of disease complications and associated symptoms.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Novel and emerging therapies for cholestatic liver diseases. (Pubmed Central) - Jul 4, 2019
...While PBC is currently treated with ursodeoxycholic acid (UDCA) and obeticholic acid (OCA), many fail treatment, and we have yet to find an effective therapy for PSC...This review summarizes our current understanding of the role of bile acids in the pathophysiology of cholestatic liver diseases, presents the rationale for already approved medical therapies, and discusses novel pharmacologic therapies under investigation. (word count: 188).
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Obeticholic acid in primary biliary cholangitis. (Pubmed Central) - Jun 20, 2019
Pruritus (and serious adverse effects) was observed more frequently in obeticholic acid-treated patients than in controls, in spite of a decrease in serum bile acid concentration. These results are encouraging, but more studies are needed on clinical efficacy and safety before obeticholic acid can be widely recommended.
- |||||||||| INT-767 / Intercept
Preclinical, Journal: Long-term Administration of Nuclear Bile Acid Receptor FXR Agonist Prevents Spontaneous Hepatocarcinogenesis in Abcb4(-/-) Mice. (Pubmed Central) - Jun 15, 2019
Here we tested chemical FXR activation by administering for 15 months the dual FXR/ membrane G protein-coupled receptor (TGR5) agonist INT-767 (6α-ethyl-3α,7α,23-trihydroxy-24-nor-5β-cholan-23-sulphate) to Fxr and Abcb4 mice...Thus, long term activation of FXR is able to reduce BA pool, reprogram BA metabolism and prevent HCC. These data provide the impetus to address the bona fide therapeutic potential of FXR activation in disease with BA-associated development of HCC.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Combined obeticholic acid and apoptosis inhibitor treatment alleviates liver fibrosis. (Pubmed Central) - Jun 14, 2019
Our study demonstrated that OCA inhibits HSCs activation/proliferation partially by regulating BA homeostasis and thereby inhibiting activation of HSCs. The findings in this study suggest that combined use of apoptosis inhibitor and OCA at lower dosage represents a novel therapeutic strategy for liver fibrosis.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: HNF4α regulates CSAD to couple hepatic taurine production to bile acid synthesis in mice. (Pubmed Central) - May 30, 2019
Bile acids and cytokines repress hepatic CSAD, which closely couples taurine production to bile acid synthesis in mice. The species-specific regulation of CSAD reflects the differential preference of bile acid conjugation to glycine and taurine in humans and mice, respectively.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Modern treatment of primary biliary cholangitis (Pubmed Central) - May 26, 2019
...This changed at the end of 2016 when obeticholic acid was licensed in Europe for PBC patients not responding to UDCA...One issue that remains unresolved is the therapeutic management of extrahepatic symptoms associated with PBC, namely fatigue and pruritus, which are the main factors influencing the quality of life of affected individuals. Their pathophysiological basis is poorly understood and treatment remains unsatisfactory.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: A facile synthesis of ursodeoxycholic acid and obeticholic acid from cholic acid. (Pubmed Central) - May 11, 2019
In the straightforward synthetic route for preparation of UDCA and OCA, most of the reaction steps have high conversions with average yields of 94% and 92%, and overall yield up to 65% (7 steps) and 36% (11 steps) from cholic acid, respectively. This promising route offers economical and efficient strategies for potential large-scale production of UDCA and OCA.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: A Practical Review of Primary Biliary Cholangitis for the Gastroenterologist. (Pubmed Central) - May 8, 2019
The only currently approved second-line option for patients who do not achieve adequate biochemical response or are intolerant to UDCA is the novel farnesoid X receptor agonist obeticholic acid. Off-label use of peroxisome proliferator-activated receptor agonists, including the fibrate class of drugs where available, is also recognized as an option for patients.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Splenic dendritic cell involvement in FXR-mediated amelioration of DSS colitis. (Pubmed Central) - May 7, 2019
...We show that FXR activation by obeticholic acid (OCA) has systemic anti-inflammatory effects that include increased levels of plasma IL-10, inhibition of both DSS-colitis associated decrease in splenic dendritic cells (DCs) and increase in Tregs...Together, our data suggest that OCA treatment elicits an anti-inflammatory immune status including retention of DCs in the spleen, which is associated with decreased colonic inflammation. Pharmacological FXR activation is therefore an attractive new drug target for treatment of IBD.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: PRIMARY BILIARY CHOLANGITIS: THERAPEUTIC APPROACH IN THE MODERN ERA (Pubmed Central) - May 5, 2019
...Recently, obeticholic acid (OCA) was officially approved as an add-on treatment in patients not responding or intolerant to UDCA...Novel treatment concepts and potential therapeutic options are under investigation. The current review addresses treatment aspects of PBC, while shedding light on the latest updates in patients' management and follow-up.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Primary biliary cholangitis : an update (Pubmed Central) - Apr 28, 2019
Fibrates appear to be a promising alternative. Liver transplantation yields excellent outcomes in advanced cases.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Current Treatment Options for Primary Biliary Cholangitis. (Pubmed Central) - Apr 24, 2019
Off-label use of fibrates has also been reported to be effective. Several new therapies are in development and may further add to the treatment options available to patients with primary biliary cholangitis.
- |||||||||| Remitch (nalfurafine) / Tanabe Research Labs, Toray, Ocaliva (obeticholic acid) / Intercept
Review, Journal: Work in Progress: Drugs in Development. (Pubmed Central) - Apr 24, 2019
We consider compounds acting on the farnesoid X receptor/fibroblast growth factor 19 pathway, fibrates and other agonists of the peroxisome proliferator-activated receptor family, transmembrane-G-protein-receptor-5 agonists, and several immunological agents. We also consider the roles of bile acid reuptake inhibitors, nalfurafine, and fibrates in pruritus management.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Review, Journal: Current Status of Liver Transplantation for Primary Biliary Cholangitis. (Pubmed Central) - Apr 24, 2019
Several scoring systems have been developed and validated to assess treatment response and transplant-free survival in patients. Although PBC is a favorable indication for LT, recurrence of PBC may occur and requires biopsy for diagnosis.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Trial completion, Trial completion date: POISE: Phase 3 Study of Obeticholic Acid in Patients With Primary Biliary Cirrhosis (clinicaltrials.gov) - Apr 23, 2019
P3, N=217, Completed,
Although PBC is a favorable indication for LT, recurrence of PBC may occur and requires biopsy for diagnosis. Active, not recruiting --> Completed | Trial completion date: Jun 2018 --> Dec 2018
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Farnesoid X receptor activation protects the kidney from ischemia-reperfusion damage. (Pubmed Central) - Apr 17, 2019
In further experiments administering 6-ECDCA to renal proximal tubular cells cultured under hypoxia, the renoprotective effects of FXR activation were associated with inhibition of oxidative and ER stress and with increased antioxidant activity. In conclusion, FXR agonists may have a therapeutic role in conditions associated with ischemic kidney damage.
- |||||||||| Firazyr (icatibant) / Takeda, Ocaliva (obeticholic acid) / Intercept, INT-747 / Intercept
Preclinical, Journal: Farnesoid X Receptor Activation Modulates Calcium Homeostasis in Rat Aortic Vascular Smooth Muscle Cells. (Pubmed Central) - Apr 14, 2019
No abstract available ...agonists GW4064 and INT-747 increased the protein abundance of ATâ‚‚R and Bâ‚‚R in rat aortic VSMCs...were partially reversed by ATâ‚‚R and Bâ‚‚R blockade with PD123319 and HOE140, respectively...suggest that FXR regulates vascular tension by modulating extracellular Ca²⺠influx and intracellular Ca²âºrelease from the sarcoplasmic reticulum via activation of an ATâ‚‚R-Bâ‚‚R pathway in rat aortic VSMCs.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Clinical, Journal: Are Clinicians Ready for Safe Use of Stratified Therapy in Primary Biliary Cholangitis (PBC)? A Study of Educational Awareness. (Pubmed Central) - Apr 11, 2019
Significant knowledge gaps in clinicians managing PBC presents a problem in optimizing care. It is perhaps not surprising that knowledge of emerging second-line therapies is low, however more concerning is sub-optimal use of UDCA in real-life practice and the lack of confidence at assessing treatment response which should be a routine part of clinical practice to assess risk of disease progression and will be key in delivering stratified medicine.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Preclinical, Journal: Human-specific dual regulations of FXR-activation for reduction of fatty liver using in vitro cell culture model. (Pubmed Central) - Apr 4, 2019
...The hepatocytes were exposed to natural or synthetic farnesoid X receptor-ligands (bile acids, GW4064, obeticholic acid) together with or after To901317...The accumulated triglyceride was significantly degraded by the farnesoid X receptor-ligands only in the human cells accompanied with the up-regulations of peroxisome proliferator-activated receptor-α and fatty acid β-oxidation. Farnesoid X receptor-ligands can be therapeutic agents for treating human fatty liver through dual effects on inhibition of lipogenesis and on enhancement of lipolysis.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: Advances in the treatment of primary biliary cholangitis (Pubmed Central) - Mar 29, 2019
Obeticholic acid, a farnesoid X receptor agonist, has been approved by FDA in May 2016 for patients who have no response to UDCA treatment or cannot tolerate such treatment. Other drugs such as fibrates, glucocorticoids, immunosuppressants, biological agents, and mesenchymal stem cells are gradually used in clinical practice and bring new hope to patients with refractory PBC.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Biomarker, Clinical, Journal: Risk factors and therapeutic strategies for primary biliary cholangitis patients with poor prognosis (Pubmed Central) - Mar 29, 2019
These patients need early diagnosis and urgent treatment. This article discusses how to identify the PBC patients with poor prognosis early from the aspects of biochemical response, disease features, and biomarkers, and reviews the progress in related complementary therapies and new drugs including Ocaliva, Fibrates, UDCA-derived drugs, and molecular targeted drugs.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Journal: The effects of farnesoid X receptor activation on arachidonic acid metabolism, NF-kB signaling and hepatic inflammation. (Pubmed Central) - Mar 25, 2019
...Mice were fed an HFD to induce NAFLD and then treated with the FXR ligand obeticholic acid (OCA)...The CYP450 epoxygenase pan-inhibitor gemfibrozil fully abolished the protective effect of OCA, indicating that OCA-mediated inhibition of NF-kB signaling was EET-dependent...Farnesoid X receptor (FXR) activation reprogramed arachidonate metabolism by inducing CYP450 epoxygenase expression and EET production. In vitro, FXR-mediated NF-kB inhibition, required active CYP450 epoxygenases.
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Trial completion date, Trial primary completion date: Role of Obeticholic Acid in the Patients of NAFLD With Raised ALT (clinicaltrials.gov) - Mar 6, 2019
P=N/A, N=150, Not yet recruiting,
Not yet recruiting --> Recruiting Trial completion date: Jun 2019 --> Oct 2019 | Trial primary completion date: Apr 2019 --> Jul 2019
- |||||||||| Ocaliva (obeticholic acid) / Intercept
Clinical, Journal: Practical strategies for pruritus management in the obeticholic acid-treated patient with PBC: proceedings from the 2018 expert panel. (Pubmed Central) - Mar 1, 2019
These recommendations include a comprehensive list of management strategies (including over-the-counter, prescription, and alternative therapies), guidance on titration of OCA to minimize pruritus severity, and an algorithm that outlines a practical approach to follow up with patients receiving OCA, to better assess and manage pruritus symptoms. Pruritus associated with OCA therapy is dose dependent and often manageable, and with the proper education and tools, most pruritus cases can be effectively managed to minimize treatment discontinuation.
|
