A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH

BACKGROUND Management of nonalcoholic steatohepatitis (NASH) is an unmet clinical need. Lanifibranor is a pan-PPAR (peroxisome proliferator–activated receptor) agonist that modulates key metabolic, inflammatory, and fibrogenic pathways in the pathogenesis of NASH. METHODS In this phase 2b, double-bl...

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Autores: Francque, Sven M., Bedossa, Pierre, Ratziu, Vlad, Anstee, Quentin M., Romero Gómez, Manuel, Abdelmalek, Manal F.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/138295
Acceso en línea:https://hdl.handle.net/11441/138295
https://doi.org/10.1056/NEJMoa2036205
Access Level:acceso abierto
Palabra clave:Pan-PPAR Agonist
Lanifibranor
NASH
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spelling A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASHFrancque, Sven M.Bedossa, PierreRatziu, VladAnstee, Quentin M.Romero Gómez, ManuelAbdelmalek, Manal F.Pan-PPAR AgonistLanifibranorNASHBACKGROUND Management of nonalcoholic steatohepatitis (NASH) is an unmet clinical need. Lanifibranor is a pan-PPAR (peroxisome proliferator–activated receptor) agonist that modulates key metabolic, inflammatory, and fibrogenic pathways in the pathogenesis of NASH. METHODS In this phase 2b, double-blind, randomized, placebo-controlled trial, patients with noncirrhotic, highly active NASH were randomly assigned in a 1:1:1 ratio to receive 1200 mg or 800 mg of lanifibranor or placebo once daily for 24 weeks. The pri- mary 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. Secondary end points included resolution of NASH and regression of fibrosis. RESULTS 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. The percentage of patients who had a decrease of at least 2 points in the SAF-A score without worsening of fibrosis was significantly higher among those who received the 1200-mg dose, but not among those who received the 800-mg dose, of lanifibranor than among those who received placebo (1200-mg dose vs. placebo, 55% vs.33%, P = 0.007; 800-mg dose vs. placebo, 48% vs. 33%, P = 0.07). The results favored both the 1200-mg and 800-mg doses of lanifibranor over placebo for resolution of NASH without worsening of fibrosis (49% and 39%, respectively, vs. 22%), improvement in fibrosis stage of at least 1 without worsening of NASH (48% and 34%, respectively, vs. 29%), and resolution of NASH plus improvement in fibrosis stage of at least 1 (35% and 25%, respectively, vs. 9%). Liver enzyme levels decreased and the levels of the majority of lipid, inflammatory, and fibrosis biomarkers improved in the lanifibranor groups. The dropout rate for adverse events was less than 5% and was similar across the trial groups. Diarrhea, nausea, peripheral edema, anemia, and weight gain occurred more frequently with lanifibranor than with placebo. CONCLUSIONS In this phase 2b trial involving patients with active NASH, the percentage of patients who had a decrease of at least 2 points in the SAF-A score without worsening of fibrosis was significantly higher with the 1200-mg dose of lanifibranor than with placebo. These findings support further assessment of lanifibranor in phase 3 trials. (Funded by Inventiva Pharma; NATIVE ClinicalTrials.gov number, NCT03008070Massachusetts Medical SocietyMedicina2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11441/138295https://doi.org/10.1056/NEJMoa2036205reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésNew England Journal OF mEDICINE, 385 (17), 1547-1558.http://doi.org/10.1056/NEJMoa2036205info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1382952026-06-17T12:51:07Z
dc.title.none.fl_str_mv A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH
title A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH
spellingShingle A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH
Francque, Sven M.
Pan-PPAR Agonist
Lanifibranor
NASH
title_short A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH
title_full A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH
title_fullStr A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH
title_full_unstemmed A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH
title_sort A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH
dc.creator.none.fl_str_mv Francque, Sven M.
Bedossa, Pierre
Ratziu, Vlad
Anstee, Quentin M.
Romero Gómez, Manuel
Abdelmalek, Manal F.
author Francque, Sven M.
author_facet Francque, Sven M.
Bedossa, Pierre
Ratziu, Vlad
Anstee, Quentin M.
Romero Gómez, Manuel
Abdelmalek, Manal F.
author_role author
author2 Bedossa, Pierre
Ratziu, Vlad
Anstee, Quentin M.
Romero Gómez, Manuel
Abdelmalek, Manal F.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Medicina
dc.subject.none.fl_str_mv Pan-PPAR Agonist
Lanifibranor
NASH
topic Pan-PPAR Agonist
Lanifibranor
NASH
description BACKGROUND Management of nonalcoholic steatohepatitis (NASH) is an unmet clinical need. Lanifibranor is a pan-PPAR (peroxisome proliferator–activated receptor) agonist that modulates key metabolic, inflammatory, and fibrogenic pathways in the pathogenesis of NASH. METHODS In this phase 2b, double-blind, randomized, placebo-controlled trial, patients with noncirrhotic, highly active NASH were randomly assigned in a 1:1:1 ratio to receive 1200 mg or 800 mg of lanifibranor or placebo once daily for 24 weeks. The pri- mary 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. Secondary end points included resolution of NASH and regression of fibrosis. RESULTS 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. The percentage of patients who had a decrease of at least 2 points in the SAF-A score without worsening of fibrosis was significantly higher among those who received the 1200-mg dose, but not among those who received the 800-mg dose, of lanifibranor than among those who received placebo (1200-mg dose vs. placebo, 55% vs.33%, P = 0.007; 800-mg dose vs. placebo, 48% vs. 33%, P = 0.07). The results favored both the 1200-mg and 800-mg doses of lanifibranor over placebo for resolution of NASH without worsening of fibrosis (49% and 39%, respectively, vs. 22%), improvement in fibrosis stage of at least 1 without worsening of NASH (48% and 34%, respectively, vs. 29%), and resolution of NASH plus improvement in fibrosis stage of at least 1 (35% and 25%, respectively, vs. 9%). Liver enzyme levels decreased and the levels of the majority of lipid, inflammatory, and fibrosis biomarkers improved in the lanifibranor groups. The dropout rate for adverse events was less than 5% and was similar across the trial groups. Diarrhea, nausea, peripheral edema, anemia, and weight gain occurred more frequently with lanifibranor than with placebo. CONCLUSIONS In this phase 2b trial involving patients with active NASH, the percentage of patients who had a decrease of at least 2 points in the SAF-A score without worsening of fibrosis was significantly higher with the 1200-mg dose of lanifibranor than with placebo. These findings support further assessment of lanifibranor in phase 3 trials. (Funded by Inventiva Pharma; NATIVE ClinicalTrials.gov number, NCT03008070
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/138295
https://doi.org/10.1056/NEJMoa2036205
url https://hdl.handle.net/11441/138295
https://doi.org/10.1056/NEJMoa2036205
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv New England Journal OF mEDICINE, 385 (17), 1547-1558.
http://doi.org/10.1056/NEJMoa2036205
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Massachusetts Medical Society
publisher.none.fl_str_mv Massachusetts Medical Society
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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