- |||||||||| aldafermin (NGM282) / NGM Biopharma
Preclinical, Review, Journal: THE ROLE OF FGF19 IN METABOLIC REGULATION: INSIGHTS FROM PRECLINICAL MODELS TO CLINICAL TRIALS. (Pubmed Central) - Aug 22, 2024 Moreover, we provide a comprehensive overview of clinical trials involving a FGF19 analog called aldafermin, emphasizing promising results in diseases such as non-alcoholic steatohepatitis and diabetes. Therefore, we aim to foster a deeper understanding of FGF19 role and encourage further exploration of its clinical applications, thereby advancing the field and offering innovative approaches to address the escalating global health challenge of obesity and related metabolic conditions.
- |||||||||| aldafermin (NGM282) / NGM Biopharma
Efficacy and safety of FGF-analogs for the treatment of MASH: a systematic review and meta-analysis (Poster Area) - Apr 2, 2024 - Abstract #EASLILC2024EASL_ILC_2098; Notably, only Aldafermin 1 mg displayed an increase in MASH resolution with no worsening of fibrosis and no significant side effects compared to placebo. Further studies with larger sample size and extended follow-up are essential for comprehensively assessing the sustained efficacy and safety of the drug.
- |||||||||| aldafermin (NGM282) / NGM Biopharma
Journal: FGF19 and its analog Aldafermin cooperate with MYC to induce aggressive hepatocarcinogenesis. (Pubmed Central) - Feb 19, 2024 In particular, even a short systemic treatment with recombinant proteins triggered rapid appearance of proliferative foci of MYC-expressing hepatocytes. The fact that FGF19 analog Aldafermin is not fully devoid of the hormone's oncogenic properties raises concerns in the context of its potential use for patients with damaged, mutation-prone liver.
- |||||||||| Comparative efficacy of pharmacologic therapies in MASH: Systematic review and meta-analysis (New Hall) - Jan 6, 2024 - Abstract #APASL2024APASL_707;
For MRI-PDFF response, Aldafermin (SUCRA = 92.61), Efruxifermin (SUCRA = 81.00) and Resmetirom (SUCRA = 55.54) had the highest probability of being ranked the most effective intervention for achieving MRI-PDFF response at week 12. These data provide relative rank-order efficacy of various MASH therapies in terms of improvements in MRI-PDFF.
- |||||||||| aldafermin (NGM282) / NGM Biopharma
Fibroblast growth factor 19 cooperates with Myc to promote liver carcinogenesis (Poster Area) - Apr 12, 2023 - Abstract #EASLILC2023EASL_ILC_2305; Moreover, we suggest that aldafermin might keep oncogenic properties in this context. Since Myc pathway is often deregulated in patients with NASH or cirrhosis, our results suggest a precautionary approach with regard to the potential adverse effects of FGF analogs in these patients.
- |||||||||| resmetirom (MGL-3196) / Madrigal Pharma, aldafermin (NGM282) / NGM Biopharma
Hepatic fat and liver volume reductions (Poster Area) - Apr 12, 2023 - Abstract #EASLILC2023EASL_ILC_1914; P2 The impact of SC and LV correction is great on the concomitant fibrosis around steatosis, but minimal on the concomitant fibrosis around ballooning. Therefore, concomitant analyses with digital pathology can augment the interpretation of the mechanism of action of drugs in NASH as well as allow for a better understanding of the impact these drugs have on histopathology and should be considered in future trials.
- |||||||||| Update on clinical management of Primary Biliary Cirrhosis (3F Plenary Hall) - Dec 18, 2022 - Abstract #APASL2023APASL_237;
Novel PPAR agonists for PBC including elafibranor (PPAR-ad), saroglitazar (PPARa/g), and seladelpar(PPARd) showed a favorable biochemical response in phase 2 clinical trials. Lastly, RCT of linerixibat (an ileal bile acid transporter inhibitor) in PBC patients showed improvement in pruritus severity.
- |||||||||| linerixibat (GSK2330672) / GSK, seladelpar (MBX-8025) / CymaBay, aldafermin (NGM282) / NGM Biopharma
Retrospective data, Review: Efficacy and safety of pharmacological interventions for pruritus in primary biliary cholangitis: A systematic review and meta-analysis. (Pubmed Central) - Nov 8, 2022 UDCA, bezafibrate, OCA, rifampicin, NGM282 and others may improve blood γ-glutamyl transpeptidase (γ-GGT) (p < 0.05), but due to the high heterogeneity and the limitation of research samples, a clear conclusion cannot be drawn...Due to the heterogeneity in the published studies, based on the present review, we cannot explicitly recommend any specific drug for the treatment of PBC-related pruritus. Systematic Review Registration: link-https://osf.io/2g8ya, identifier 10.17605/OSF.IO/2G8YA.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, aldafermin (NGM282) / NGM Biopharma
Preclinical, Journal: Systemic ASBT inactivation protects against liver damage in obstructive cholestasis in mice. (Pubmed Central) - Sep 29, 2022 In a second (wild-type) mouse model, a combination of obeticholic acid (OCA) and intestine-restricted ASBT inhibition was used to lower the bile salt pool size before BDL...Novel treatment approaches against cholestatic liver disease (resulting in reduced or blocked flow of bile) involve non-absorbable inhibitors of the bile acid transport protein ASBT, but these are not always effective and/or can cause unwanted side effects. In this study, we demonstrate that systemic inhibition/inactivation of ASBT protects mice against developing severe cholestatic liver injury after bile duct ligation, by reducing bile salt pool size and increasing renal bile salt excretion.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, resmetirom (MGL-3196) / Madrigal Pharma, aldafermin (NGM282) / NGM Biopharma
Clinical, Retrospective data, Review, Journal: Pharmacotherapeutic Impact on Nonalcoholic Steatohepatitis Histology: A Systematic Review and Network Meta-analysis. (Pubmed Central) - Jul 13, 2022 Multiple interventions were found to improve individual histologic scores across secondary outcome analyses and are detailed below. This novel systematic review and network meta-analysis represents the most comprehensive investigation to date regarding the pharmacotherapeutic options for biopsy-proven NASH using current recommended histologic endpoints.
- |||||||||| aldafermin (NGM282) / NGM Biopharma
Aldafermin rebalances collagen turnover in patients with NASH and liver fibrosis in the ALPINE 2/3 study (Poster Area) - May 12, 2022 - Abstract #EASLILC2022EASL_ILC_1811; Given the invasive and heterogeneous nature of liver biopsy, these novel, non-invasive fibrosis markers may have the potential to obviate the limitations of liver biopsy by providing important information regarding the state of the liver and extracellular matrix turnover. Non-invasive assessment of liver disease except NAFLD
- |||||||||| aldafermin (NGM282) / NGM Biopharma
Enrollment closed, Trial completion date, Trial primary completion date: Study of Aldafermin (NGM282) in Subjects With Compensated Cirrhosis (ALPINE 4) (clinicaltrials.gov) - Mar 18, 2022 P2b, N=160, Active, not recruiting, Non-invasive assessment of liver disease except NAFLD Recruiting --> Active, not recruiting | Trial completion date: Sep 2022 --> Mar 2023 | Trial primary completion date: Jun 2022 --> Dec 2022
- |||||||||| Ocaliva (obeticholic acid) / Intercept, aldafermin (NGM282) / NGM Biopharma, lanifibranor (IVA337) / Inventiva
Spontaneous and drug-induced histological changes in nonalcoholic steatohepatitis: an assessment by meta-analysis of trials (Poster Area) - Mar 16, 2022 - Abstract #EASLILC2022EASL_ILC_1689; Recruiting --> Active, not recruiting | Trial completion date: Sep 2022 --> Mar 2023 | Trial primary completion date: Jun 2022 --> Dec 2022 Since semaglutide and pioglitazone appear to be more effective on NASH activity while aldafermin, lanifibranor and obeticholic acid perform better on the evolution of fibrosis, combination therapies should be assessed prospectively in subjects who are less likely to improve spontaneously over time, i.e. older patients with biochemically active disease.
- |||||||||| aldafermin (NGM282) / NGM Biopharma
Quantitative assessment of liver fibrosis in NASH patients (Poster Area) - Mar 16, 2022 - Abstract #EASLILC2022EASL_ILC_1149; P2 Samples from a Phase 2 clinical trial with aldafermin (NGM282), an engineered fibroblast growth factor 19 analogue, were used to develop a novel image analysis readout for liver fibrosis... In summary, immunohistochemistry-based quantitative pathology endpoints may identify drug effects that are not captured by categorical CRN endpoints.
- |||||||||| aldafermin (NGM282) / NGM Biopharma
Journal: A short report on NGM282/aldafermin for the treatment of non-alcoholic steatohepatitis [NASH]. (Pubmed Central) - Mar 3, 2022 Aldafermin is an FGF-19 analogue that has shown promising results in non-alcoholic steatohepatitis animal models, with preclinical data supporting its safety profile, specifically, the lack of a tumourogenic effect. The pre-clinical data presented in this paper support the clinical development of aldafermin, and indeed early data from several phase II clinical trials report promising results in relation to the ability of aldafermin to improve the histologic features of NASH particularly in relation to a reduction in liver fat content.
- |||||||||| aldafermin (NGM282) / NGM Biopharma
Trial completion, Trial completion date: Evaluation of Efficacy, Safety and Tolerability of Aldafermin in a Phase 2b, Randomized, Double-blind, Placebo-controlled, Multi-center Study In Subjects With Nonalcoholic Steatohepatitis and Stage 2/3 Fibrosis (ALPINE 2/3) (clinicaltrials.gov) - Jan 6, 2022 P2b, N=171, Completed, Recruiting --> Completed Active, not recruiting --> Completed | Trial completion date: Sep 2021 --> Mar 2021
- |||||||||| Humira (adalimumab) / Eisai, AbbVie
Journal: Recent advances in the treatment of primary sclerosing cholangitis. (Pubmed Central) - Nov 12, 2021 In observational studies of effects of biological therapy in patients with IBD/PSC adalimumab was associated with reduction in ALP. Results of liver transplantation are favorable but recurrence can be of clinical relevance particularly in patients transplanted before the age of 40.
- |||||||||| Review, Journal: Evolving role for pharmacotherapy in NAFLD/NASH. (Pubmed Central) - Oct 27, 2021
Outcomes of promising phase 2 trials in adults with NASH are also available and those have investigated agents including the FGF19 analogue NGM282, the GLP1 agonist liraglutide, the FGF21 analogue Pegbelfermin, the SGLT2 inhibitor Empagliflozin, the ketohexokinase inhibitor PF-06835919, the acetyl-coenzyme A carboxylase inhibitor GS-0976 and the chemokine receptor antagonist Cenicriviroc. Completed and ongoing clinical trials emphasize the need for a more nuanced understanding of the phenotypes of subgroups within NAFLD that may respond to an individualized approach to pharmacotherapy.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, aldafermin (NGM282) / NGM Biopharma
[VIRTUAL] RESISTANCE TO FGF19 SIGNALING PREDICTS THE SEVERITY OF HEPATIC STEATOSIS DURING CROHN’S DISEASE () - Oct 21, 2021 - Abstract #AASLD2021AASLD_1867; Although the direction of causality is unresolved, either suppression of FGF19 production or disrupting its receptor’s (FGFR4) signaling pathway are expected to both promote de novo lipogenesis and reduce fatty acid oxidation . Future directions will include unravelling the molecular mechanism of FGF19 resistance and determining if it predicts clinical response to FGF19 relevant therapeutics (e .g .
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