NGM282, an FGF19 analogue, in primary sclerosing cholangitis: A nebulous matter

Tabibian, James H.; Lindor, Keith D.

doi:10.1016/j.jhep.2018.12.006

Cited by 6 publications

(6 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite that no significant changes in ALP from baseline were observed, fibrosis biomarkers (Enhanced Liver Fibrosis test score and Pro-C3) were significantly improved in the treatment group [77]. This trial has stimulated discussion about the most appropriated target in PSC [88]. There are no established endpoints in PSC.…”

Section: Fxr Agonistsmentioning

confidence: 96%

The Management of Cholestatic Liver Diseases: Current Therapies and Emerging New Possibilities

Mazzetti

Marconi

Mancinelli

et al. 2021

JCM

View full text Add to dashboard Cite

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are two chronic cholestatic liver diseases affecting bile ducts that may progress to biliary cirrhosis. In the past few years, the increasing knowledge in the pathogenesis of both diseases led to a growing number of clinical trials and possible new targets for therapy. In this review, we provide an update on the treatments in clinical use and summarize the new drugs in trials for PBC and PSC patients. Farnesoid X Receptor (FXR) agonists and Pan-Peroxisome Proliferator-Activated Receptor (PPAR) agonists are the most promising agents and have shown promising results in both PBC and PSC. Fibroblast Growth Factor 19 (FGF19) analogues also showed good results, especially in PBC, while, although PBC and PSC are autoimmune diseases, immunosuppressive drugs had disappointing effects. Since the gut microbiome could have a potential role in the pathogenesis of PSC, recent research focused on molecules that could change the microbiome, with good results. The near future of the medical management of these diseases may include new treatments or a combination of multiple drugs targeting different signaling pathways at different stages of the diseases.

show abstract

Section: Fxr Agonistsmentioning

confidence: 96%

The Management of Cholestatic Liver Diseases: Current Therapies and Emerging New Possibilities

Mazzetti

Marconi

Mancinelli

et al. 2021

JCM

View full text Add to dashboard Cite

show abstract

“…49 It is worth mentioning that NGM282 (Aldafermin), an engineered FGF19 analogue, has also been utilized in clinical trials for patients with Non-alcoholic steatohepatitis (NASH), with promising outcomes including the reduction in absolute liver fat content. [51][52][53][54] In a phase 2 trial with NASH patients, Aldafermin was shown to reduce liver fat and generated a trend towards the improvement of hepatic fibrosis. 52…”

Section: F I G U R E 2 List Of Three Categories Of Potential Fgf21 Ba...mentioning

confidence: 99%

Hepatic hormone FGF21 and its analogues in clinical trials

Shao

Jin

2022

Chronic Diseases and Translational Medicine

View full text Add to dashboard Cite

Fibroblast growth factor 21 (FGF21) is a fasting or stress inducible metabolic hormone produced mainly in the liver. It plays important roles in regulating both glucose and lipid homeostasis via interacting with a heterodimeric receptor complex comprising FGF receptor 1 (FGFR1) and β‐klotho (KLB). For the past decade, great effort has been made on developing FGF21 derivatives or specific FGF21 receptor agonists into therapeutic agents for various metabolic disorders including type 2 diabetes (T2D), obesity, and more importantly, nonalcoholic fatty liver disease (NAFLD). Here we have reviewed FGF21 gene and protein structures, its expression pattern, cellular signaling cascades that mediate FGF21 production and function. We have then summarized the six clinical trials utilizing four FGF21 analogues. Finally, two recent literatures on the development of GLP‐1 and FGF21 dual agonists were presented briefly.

show abstract

“…Indeed, this trial has awakened again the discussion around limitations of ALP as surrogate endpoint of novel therapies in PSC [81]. It is of note that this trial included also patients with dominant strictures, small-duct PSC, autoimmune hepatitis and cirrhosis, and this could have hampered the demonstration of the potential beneficial effects of the drug [82]. Despite it is probably likely that ALP is not the best treatment target, whether improvement of other explanatory markers translates into (1) improvement in hard outcomes, (2) prevention of cholangiocarcinoma needs also to be proven [82] (ClinicalTrials.gov Identifier: NCT02704364).…”

Section: Fxr Agonistsmentioning

confidence: 99%

Multiple therapeutic targets in rare cholestatic liver diseases: Time to redefine treatment strategies

Gerussi

D’Amato

Cristoferi

et al. 2020

Annals of Hepatology

View full text Add to dashboard Cite

Primary biliary cholangitis and primary sclerosing cholangitis are rare diseases affecting the bile ducts and the liver. The limited knowledge of their pathogenesis leads to limited therapeutic options. Nevertheless, the landscape of novel therapies for these cholangiopathies is now rapidly changing, providing new treatment opportunities for patients and clinicians involved in their care. The aim of this review is to summarize the evidence of novel molecules under investigation for primary biliary cholangitis and primary sclerosing cholangitis and to discuss how they can potentially change current treatment paradigms.

show abstract

NGM282, an FGF19 analogue, in primary sclerosing cholangitis: A nebulous matter

Cited by 6 publications

References 16 publications

The Management of Cholestatic Liver Diseases: Current Therapies and Emerging New Possibilities

The Management of Cholestatic Liver Diseases: Current Therapies and Emerging New Possibilities

Hepatic hormone FGF21 and its analogues in clinical trials

Multiple therapeutic targets in rare cholestatic liver diseases: Time to redefine treatment strategies

Contact Info

Product

Resources

About