RR, 1.7 [lanifibranor 1,200 mg vs placebo] and 34 percent vs 29 percent; RR, - Debrecen, Debrecen, Hajdu-Bihar County, Hungary, 4025, Debreceni Egyetem Klinikai Kzpont Kenzy Gyula Campus, Dl-pesti Centrumkrhz - Orszgos Hematolgiai s Infektolgiai Intzet, Jerusalem, Jerusalem District, Israel, 9103102, Jerusalem, Jerusalem District, Israel, 9112001, Nahariya, Northern District, Israel, 22100, Be'er Sheva, Southern District, Israel, 84101, San Giovanni Rotondo, Foggia, Italy, 71013, Centro de Investigacin y Gastroenterologa, Cuauhtmoc, Ciudad De Mxico, Mexico, 06700, Contact: Alma Laura Ladron De Guevara Cetina, Doctor, Contact: Laura Esthela Cisneros Garza, Doctor, Hospital Universitario Doctor Jos Eleuterio Gonzalez, Amsterdam Universitair Medische Centra - Vrije Universiteit Medisch Centrum, Amsterdam, Noord-Holland, Netherlands, 1081 HV, Tilburg, North Brabant, Netherlands, 5000 LC, Rotterdam, Zuid-Holland, Netherlands, 3015 GD, Niepubliczny Zaklad Opieki Zdrowotnej Centrum Badan Klinicznych, Contact: Orkwiszewska-Nalewajko Anna, Doctor, Mysowice, Silesian Voivodeship, Poland, 41-400, Contact: Magdalena Olszanecka-Glinianowicz, Doctor, Synexus Polska Sp. Semaglutide, but not . The complex pathophysiology of NASH may require targeting multiple pathways rather than a single pathway for successful treatment, said the researchers. Epub 2020 Oct 8. The online version is available here : Elafibranor, an Agonist of the Peroxisome Proliferator-activated Receptor- and -, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening The study was published online October 20 in The New England Journal of Medicine. Nonetheless, the patient with the severe case recovered after drug discontinuation for 12 days, without reoccurrence after treatment resumption. Peroxisome proliferatoractivated receptor agonist, Wy 14 643, improves metabolic indices, steatosis and ballooning in diabetic mice with nonalcoholic steatohepatitis. Harrington WW, Britt CS, Wilson JG, et al. Currently 55, the public has been comparing Gillibrand's physical transformation from when she was young and now. Resolution of NASH without worsening fibrosis a key secondary end point also occurred more often in patients taking lanifibranor. Weight gain in DIONASH mice was relatively similar across the GAN diet feeding periods applied (GAN DIONASH mice, 43-47 0 . Gastrointestinal side effects were also more common in the treatment group. Nat Rev Gastroenterol Hepatol. Epub 2022 Jan 12. The NATIVE study enrolled 247 patients with noncirrhotic, highly active NASH, of whom 103 (42%) had type 2 diabetes mellitus and 188 (76%) had significant (moderate) or advanced fibrosis. Liver enzyme levels decreased and the levels of the majority of lipid, inflammatory, and fibrosis biomarkers improved in the lanifibranor groups. Key secondary objectives of Part 1: To assess the effect of lanifibranor compared to placebo on NASH resolution and no worsening of fibrosis . Solubility: Soluble in DMSO. Four of the peripheral oedema cases were deemed lanifibranor-related, with one being severe. Lanifibranor Placebo Stable, Moderate increase, Increase Stable, Increase CI: Confidence interval Screening EOT-20 0 20 40 60 m e a n a . Lanifibranor is a novel pan-PPAR (peroxisome proliferator-activated receptors) agonist. In mice studies, IVA337 was associated with decreased extracellular matrix (ECM) deposition and reduced expression of phosphorylated SMAD2/3-intracellular effector of transforming growth factor (TGF)-1. Of these, three-quarters had moderate/advanced fibrosis. 3D. Contrary to hepatitis C [which is] caused by a single aetiologic agent, NASH is a multifactorial, complex metabolic disorder that forms part of a systemic disease. Here at the liver meeting 2019, we gave an oral presentation summarizing our discoveries on the application of lanifibranor in Ahpra clinical model of chronic liver disease in this study, we use animals / rats with advanced chronic liver disease decompensated cirrhosis that received lanifibranor during two weeks. Participants were randomized 1:1:1 to receive lanifibranor 1,200 or 800 mg or placebo QD for 24 weeks. 2022 Jan 20;386(3):294-295. doi: 10.1056/NEJMc2118255. HHS Vulnerability Disclosure, Help The primary endpoint of a reduction of at least two points in SAF-A . By continuing to browse you agree to the storing of cookies on your device. Diarrhea, nausea, peripheral edema, anemia, and weight gain occurred more frequently with lanifibranor than with placebo. Roles of hepatic stellate cells in NAFLD: From the perspective of inflammation and fibrosis. There is a large need for drugs that prevent the development of this disease and its complications, Wakim-Fleming, who was not involved in the study, told Medscape Medical News. No effect on kidney function or bone turnover was observed. 2022 Jan 20;386(3):294. doi: 10.1056/NEJMc2118255. Price : $50 *. Lanifibranor tackles both metabolic drivers of the disease, most notably the adipose tissue dysfunction, as well as the mechanisms of inflammation and fibrogenesis inside the liver. Unable to load your collection due to an error, Unable to load your delegates due to an error, Collaborators, (Clinical Trial), Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor), A Randomised, Double-blind, Placebo-controlled, Multicentre, Phase 3 Study Evaluating Long-term Efficacy and Safety of Lanifibranor in Adult Patients With Non-cirrhotic Non-alcoholic Steatohepatitis (NASH) and Fibrosis 2 (F2)/Fibrosis 3 (F3) Stage of Liver Fibrosis, Experimental: Lanifibranor (IVA 337) (800 mg/day), Experimental: Lanifibranor (IVA 337) (1200 mg/day), 18 Years and older (Adult, Older Adult), Objective Health - Birmingham Gastroenterology Associates, Birmingham, Alabama, United States, 35209, Digestive Health Specialist of the Southeast, The Institute For Liver Health - Chandler, Chandler, Arizona, United States, 85224-5688, Del Sol Research Management - Tucson East, ARcare Center for Clinical Research - Conway, Little Rock, Arkansas, United States, 72205, North Little Rock, Arkansas, United States, 72117, Camarillo, California, United States, 93011, Chula Vista, California, United States, 91909, Chula Vista, California, United States, 91910, El Cajon, California, United States, 92020, Garden Grove, California, United States, 92844, National Research Institute - 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Because of these side effects, more large and long-term trials are needed in order to clearly assess the safety of lanifibranor and the degree of weight gain when lanifibranor is used for more than 24 weeks, Wakim-Fleming said. Lanifibranor is currently evaluated in a pivotal Phase III trial in NASHInventiva will receive a $12 million upfront, $5. Pharmacotherapy for Non-alcoholic Fatty Liver Disease Associated with Diabetes Mellitus Type 2. J Clin Transl Hepatol. Management of NASH is an unmet clinical need, said the researchers. Tsao from the Yale University School of Medicine, New Haven, Connecticut, US, in an editorial. RRs of 2.2 and 1.7 for the respective 1,200- and 800-mg doses. Lanifibranor looks like a highly efficacious drugwith a good safety profile, and if confirmed in phase 3, this would be a major breakthrough, as we currently havent seen any drug that has a significant effect on both steatohepatitis and fibrosis and this in the timeframe of 6 months, Francque told Medscape Medical News. Product name : Lanifibranor Catalog No. Pan-peroxisome proliferator-activated receptor agonist lanifibranor as a dominant candidate pharmacological therapy for nonalcoholic fatty liver disease. risk ratio [RR], 1.7; p=0.007), but not in the lanifibranor 800-mg arm (48 percent vs 33 percent; RR, Little change in these measures was seen in the placebo group. Similar to other insulin sensitizers, patients receiving lanifibranor had weight gain during treatment (2.6%-3.1% from baseline). ClinicalTrials.gov Identifier: NCT04849728, Interventional Side effects of 24-week treatment with lanifibranor included diarrhea, nausea, peripheral edema, anemia and weight gain, a part of which were very similar to those observed with pioglitazone use. Substance Class Chemical Careers. However, the mice exhibit comparable body weight to those fed a control diet and significantly lower than those fed with HFD, suggesting CCl 4 masks HFD-induced weight gain (Kubota et al. Type Small Molecule Groups Investigational Structure. The results favored both the 1200-mg and 800-mg doses of lanifibranor over placebo on several secondary end points. Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04849728. 2022 Oct 28;10(5):965-971. doi: 10.14218/JCTH.2021.00564. Of these, three-quarters had moderate/advanced fibrosis. Although regression of fibrosis can be indirectly accomplished with long-term therapy to control disease activity, the combination of therapy to control disease activity and fibrogenesis, the goals of which are reflected in the composite [secondary] endpoint could have a stronger and faster effect on disease progression, explained the researchers. The mean mRSS score at 48 weeks in the lanifibranor 400 mg, lanifibranor 600 mg, and placebo groups were lowered by 3.7, 4.3, and 4.9 from baseline, respectively. Lanifibranor is an agonist of peroxisome proliferator-activated receptors (PPARs) with EC50 values of 1,537, 866, and 206 nM for human recombinant PPAR, PPAR, and PPAR, respectively, for transactivation activity. government site. The levels of plasma adiponectin were elevated corresponding to the degree of weight gain. A total of 247 patients underwent randomization, of whom 103 (42%) had type 2 diabetes mellitus and 188 (76%) had significant (moderate) or advanced fibrosis. Lanifibranor induced a histologic improvement despite this weight gain, which could be explained by the role of adipose tissue dysfunction rather than overweight per se in the pathophysiology of NASH, and by a shift from visceral to metabolically healthy subcutaneous adipose tissue, a finding that was noted with other PPAR agonists.. Nonalcoholic Steatohepatitis - Opportunities and Challenges. The researchers attributed the weight gain to improved adipose tissue function, as reflected by the increases in serum adiponectin level with both lanifibranor 1,200 and 800 mg (17.12 and 11.95 g/ml, respectively). The primary end point was a decrease of at least 2 points in the SAF-A score (the activity part of the Steatosis, Activity, Fibrosis [SAF] scoring system that incorporates scores for ballooning and inflammation) without worsening of fibrosis; SAF-A scores range from 0 to 4, with higher scores indicating more-severe disease activity. Conclusions: 2022 Oct 13;13:958428. doi: 10.3389/fphar.2022.958428. N Engl J Med. Catalog No. sharing sensitive information, make sure youre on a federal You have reached the maximum number of saved studies (100). Lanifibranor, also known as IVA-337, is a peroxisome proliferator-activated receptors (PPAR) agonist. Inventiva (Euronext Paris and Nasdaq: IVA) and Chia Tai-Tianqing Pharmaceutical Group Co., Ltd ("CTTQ"), a subsidiary of Sino Biopharm, have entered into a licensing and collaboration agreement (the "Agreement") to develop and commercialize lanifibranor, Inventiva's proprietary compound, for the treatment of non-alcoholic steatohepatitis ("NASH") and potentially other metabolic . The researchers attributed the weight gain to improved adipose tissue function, as reflected by the increases in serum adiponectin level with both lanifibranor 1,200 and 800 mg (17.12 and 11.95 g/ml, respectively). ripheral edema, anemia, and weight gain were more common with . 2022 Oct 28;10(5):939-946. doi: 10.14218/JCTH.2022.00067. "The side effects of lanifibranor in this trial were seen in 4% of the patients, notably concerning are the severe adverse events and the weight gain." "Weight loss is considered essential and . Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V, Sanyal AJ, Sejling AS, Harrison SA; NN9931-4296 Investigators. The ability of lanifibranor to simultaneously improve pathways driving insulin resistance, reduce hepatic inflammation, and improve fibrotic response suggests an effective multitargeted mechanism of action.. N Engl J Med. GLP1 receptor activation indirectly reduces hepatic lipid accumulation but does not attenuate development of atherosclerosis in diabetic male, GLP1 receptor localization in monkey and human tissue: Novel distribution revealed with extensively validated monoclonal antibody, Reductions in insulin resistance are mediated primarily via weight loss in subjects with type 2 diabetes on semaglutide. : 927961-18- 1.2 Relevant identified uses of the substance or mixture and uses advised against Identified uses : Laboratory chemicals, manufacture of substances. Inventiva announces the presentation of five scientific abstracts at the . Listing a study does not mean it has been evaluated by the U.S. Federal Government. official website and that any information you provide is encrypted The LEGEND trial is a proof-of-concept Phase IIa clinical trial to evaluate the safety and efficacy of lanifibranor in combination with the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance 1) in patients with non-alcoholic steatohepatitis (NASH) and type 2 diabetes (T2D) The trial will be conducted in several sites in the United States and Europe with a treatment . Panjwani N, Mulvihill EE, Longuet C, et al. In a phase 2b trial, the pan-PPAR agonist lanifibranor showed promise for patients with active non-alcoholic steatohepatitis (NASH). 1.2 [lanifibranor 800 mg vs placebo]), and NASH resolution plus improvement in fibrosis stage of Affiliations. Oddzial w Gdansku, Hospital da Senhora da Oliveira - Guimares, Centro Hospitalar Universitrio Lisboa Norte - Hospital De Santa Maria, Centro Hospitalar Universitrio De So Joo, Senhora Da Hora, Portugal, Senhora Da Hora, Unidade Local Sade Alto Minho - Hospital de Santa Luzia, Fundacin de Investigacin de Diego Clinical Research, Sefako Makgatho Health Sciences University, Synexus - Mediclinic Southern Africa - Constantiaberg, Cape Town, Western Cape, South Africa, 7800, Contact: Muhammad Naayil Rajabally, Doctor, Synexus - Helderberg Clinical Research Centre - Somerset West, Somerset West, Western Cape, South Africa, 7130, Palma De Mallorca, Balearic Islands, Spain, 07120, Consorci Corporaci Sanitria Parc Taul de Sabadell, Hospital Universitario Marqus de Valdecilla, Hospital Clnico Universitario de Santiago, Santiago de Compostela, La Corua, Spain, 15706, Hospital Universitario Fundacin Alcorcn, Hospital Universitario Puerta de Hierro - Majadahonda, Contact: Marta Maria Casado Martn, Doctor, Complejo Asistencial Universitario de Leon, Hospital General Universitario Gregorio Maran, Hospital Clnico Universitario de Valencia, Contact: Maria Desamparados Escudero Garcia, Doctor, Consorci Hospital General Universitari de Valncia, Contact: Francisco Moises Diago Madrid, Doctor, Hospital Clinico Universitario Lozano Blesa, Medical Center Center of Family Medicine Plus, LLC, King's College Hospital NHS Foundation Trust, Manchester, England, United Kingdom, OL11 4AU, Preston, England, United Kingdom, PR2 9QB, Royal Surrey County Hospital NHS Foundation Trust, Surrey Quays, England, United Kingdom, GU2 7XX, Glasgow, North Lanarkshire, United Kingdom, G51 4TF, VCU Health, Gastroenterology Hepatology and Nutrition, 1200 West Broad Street, Richmond VA23298, USA, Division of Gastroenterology and Hepatology, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Belgium. Intervention: 247 adults with biopsy-confirmed, . Abstract, Editorial. the beneficial effects of lanifibranor on markers of cardiometabolic health in patients with non-cirrhotic NASH fibrosis independent of weight gain observed. No effect on kidney function or markers of bone turnover was observed. Trending News Stories from around the World. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. These are stringent end points, with a high barrier, so achieving both holds promise for truly improving the patients prognosis, he said. The most common side effects were diarrhea, nausea, peripheral edema, anemia, and weight gain, which occurred more commonly with lanifibranor.