- |||||||||| Ocaliva (obeticholic acid) / Intercept, lanifibranor (IVA337) / Inventiva
Pharmacotherapy: Past and Current (2F Room 201ABC) - Dec 18, 2022 - Abstract #APASL2023APASL_220; Although there is currently no licensed treatment for metabolic dysfunction-associated fatty liver disease, guidelines support the use of vitamin E, pioglitazone or glucagon-like peptide-1 receptor agonists in selected patients with steatohepatitis...In the interim Week 72 histological assessment of the phase 3 REGERNATE study, obeticholic acid at a dose of 25 mg daily improved liver fibrosis with no worsening of steatohepatitis...Lanifibranor, a pan-PPAR agonist, was shown to both resolve steatohepatitis and improve fibrosis in a phase 2b study. Because the pathogenesis of steatohepatitis is complicated and heterogeneous, it is believed that precision medicine and combination treatments will be needed.
- |||||||||| lanifibranor (IVA337) / Inventiva
Review, Journal: Mechanistic insights into the peroxisome proliferator-activated receptor alpha as a transcriptional suppressor. (Pubmed Central) - Dec 13, 2022 PPARα agonists are expected to be novel prescription drugs for NASH treatment, and some of them (e.g., Lanifibranor) are currently under clinical trials...Intriguingly, PPARα is known to suppress the expression of subsets of target genes under agonist treatment; however, the mechanisms of PPARα-mediated gene suppression and functions of these genes are not well understood. In this review, we summarize and discuss the mechanisms of target gene repression by PPARα and the roles of repressed target genes on hepatic lipid metabolism, fibrosis and carcinogenesis related to NALFD and NASH, and provide future perspectives for PPARα pharmaceutical potentials.
- |||||||||| Lipaglyn (saroglitazar) / Zydus Cadila, lanifibranor (IVA337) / Inventiva
PPARs – Lanifibranor and Saroglitazar (The Chateaux Deer Valley, 7815 Royal Street East, Park City) - Dec 7, 2022 - Abstract #NASHTAG2023NASH_TAG_19;
- |||||||||| elafibranor (GFT505) / Ipsen, Ocaliva (obeticholic acid) / Intercept, lanifibranor (IVA337) / Inventiva
Preclinical, Journal: Modelling fatty liver disease with mouse liver-derived multicellular spheroids. (Pubmed Central) - Nov 5, 2022 Treatment of MCLS cultures with potential anti-NAFLD drugs such as Elafibranor, Lanifibranor, Pioglitazone and Obeticholic acid shows that all can inhibit steatosis, but only Elafibranor and especially Lanifibranor inhibit fibrosis. Therefore, primary mouse MCLS cultures can be used to model acute and chronic liver disease and are suitable for the assessment of anti-NAFLD drugs.
- |||||||||| Ocaliva (obeticholic acid) / Intercept, lanifibranor (IVA337) / Inventiva
MODELING NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) AND NONALCOHOLIC STEATOHEPATITIS (NASH) WITH HUMAN MULTI-CELL-LINEAGE LIVER ORGANOIDS () - Oct 23, 2022 - Abstract #AASLD2022AASLD_1211; Normal 3D-HLOs+FFA were subjected to the treatment of leading drugs in NASH’s clinical development, such as Obeticholic acid (OCA, 1mM), Lanifibranor (LAN, 10mM), and FGF19 (10ng/ml) for 7 days to assess the functionality of organoids and drug responses. Our muti-cell-lineage 3D-HLOs provide a unique in vitro platform not only suitable for studying the pathogenic cellular interactive process in NAFLD/NASH but also for screening novel therapeutic strategies including personalized medicine.
- |||||||||| lanifibranor (IVA337) / Inventiva
Journal: An overview of current therapy options of non-alcoholic fatty liver disease. (Pubmed Central) - Jun 23, 2022 Current pharmacological treatment of NAFLD comprises screening and therapy of metabolic syndrome components and minimizing of alcohol intake. There are new substances being evaluated in clinical trials, the most promising ones are semaglutide and lanifibranor.
- |||||||||| Clinical, Review, Journal: Efficacy of peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors for treatment of non-alcoholic fatty liver disease: a systematic review. (Pubmed Central) - Apr 21, 2022
Pioglitazone, lanifibranor, and GLP1-R agonists (mostly liraglutide and semaglutide) improved individual histological features of NASH (ie, steatosis, ballooning, lobular inflammation) or achieved resolution of NASH without worsening of fibrosis. SGLT2 inhibitors (mostly empagliflozin and dapagliflozin) reduced liver fat content, as assessed by magnetic resonance-based techniques.
- |||||||||| lanifibranor (IVA337) / Inventiva
Journal: The metabolic triad of NAFLD, visceral adiposity and type 2 diabetes: implications for treatment. (Pubmed Central) - Apr 1, 2022 (pioglitazone) and pan-PPARs agonists (lanifibranor) have shown some beneficial effects on both NASH and liver fibrosis. Since NASH is a complex and multifactorial disease, it is conceivable that targeting different pathways, not only insulin resistance but also inflammation and fibrotic processes, is required to achieve NASH resolution.
- |||||||||| 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; Since NASH is a complex and multifactorial disease, it is conceivable that targeting different pathways, not only insulin resistance but also inflammation and fibrotic processes, is required to achieve NASH resolution. 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.
- |||||||||| lanifibranor (IVA337) / Inventiva
Identification of biomarkers of histological response in patients with non-cirrhotic NASH treated with Lanifibranor (Meeting Point 3) - Mar 16, 2022 - Abstract #EASLILC2022EASL_ILC_1667; These beneficial effects occur in parallel with a marked increase of adiponectin, which marks adipose tissue health and improves insulin sensitivity; the data provide further evidence that PPARγ-induced weight gain is metabolically distinct from lifestyle-related weight gain. Combined biomarker signatures have good positive and negative predictive value for histological response under lanifibranor treatment in NASH.
- |||||||||| Review, Journal: Horizon scanning of therapeutic modalities for nonalcoholic steatohepatitis. (Pubmed Central) - Feb 2, 2022
Five ongoing RCTs (5/62, 8.06%) will investigate histological progression to cirrhosis, death, or liver-related clinical outcomes. In conclusion, some therapeutic modalities showed promising benefits, but further studies are warranted to find a definite treatment of NASH which prevents progression to cirrhosis and adverse liver outcomes.
- |||||||||| Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
Clinical, Review, Journal: Non-Alcoholic Steatohepatitis (NASH) - A Review of a Crowded Clinical Landscape, Driven by a Complex Disease. (Pubmed Central) - Feb 2, 2022 At the time of writing this review, only Zydus Cadila's new drug application for Saroglitazar had been approved (2020) for NASH therapy in India...Obeticholic acid (Intercept Pharmaceuticals), Cenicriviroc (Allergan), Aramchol (Galmed Pharmaceuticals), Resmetirom (Madrigal Pharmaceuticals), Dapagliflozin and Semaglutide (Novo Nordisk) are in advanced Phase 3 clinical trials, while Belapectin (Galectin Therapeutics), MSDC-0602K (Cirius Therapeutics), Lanifibranor (Inventiva), Efruxifermin (Akero) and Tesamorelin (Theratechnologies) are expected to start Phase 3 trials soon...Hence, the development of a single therapy for NASH seems challenging and unlikely, despite the plethora of later stage trials due to report. We therefore predict that clinical, patient and company interest in pipeline and next-generation therapies will remain high for some time to come.
- |||||||||| Parmodia (pemafibrate) / Kowa
Preclinical, Journal: Human hepatic in vitro models reveal distinct anti-NASH potencies of PPAR agonists. (Pubmed Central) - Dec 28, 2021 The in vitro scoring system, based on a battery of the most performant models, namely PHH, hSKP-HPC, and LX-2 cultures, showed that elafibranor, followed by saroglitazar and pioglitazone, induced the strongest anti-NASH effects. These data corroborate available clinical data and show the relevance of these in vitro models for the preclinical investigation of anti-NASH compounds.
- |||||||||| lanifibranor (IVA337) / Inventiva
Journal: Lanifibranor and NASH resolution. (Pubmed Central) - Dec 25, 2021 These data corroborate available clinical data and show the relevance of these in vitro models for the preclinical investigation of anti-NASH compounds. No abstract available
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