Efficacy, tolerability and pharmacokinetics of survodutide, a glucagon/glucagon-like peptide-1 receptor dual agonist, in cirrhosis.

BACKGROUND & AIMS

Survodutide is a glucagon/glucagon-like peptide-1 receptor dual agonist in development for treatment of metabolic dysfunction-associated steatohepatitis (MASH). We investigated survodutide in people with cirrhosis.

METHODS

This multinational, non-randomized, open-label, phase 1 clinical trial initially evaluated a single subcutaneous (s.c.) dose of survodutide 0.3 mg in people with Child-Pugh class A, B or C cirrhosis and healthy individuals with or without overweight/obesity matched for age, sex, and weight; the primary endpoints were the area under the plasma concentration-time curve from 0 to infinity (AUC

RESULTS

In the single-dose cohorts (n = 41), mean AUC

CONCLUSIONS

Survodutide is generally tolerable in people with compensated or decompensated cirrhosis, does not require pharmacokinetic-related dose adjustment, and may improve liver-related non-invasive tests, supporting its investigation for MASH-related cirrhosis. Clinical trial number; ClinicalTrials.gov identifier: NCT05296733.

IMPACT AND IMPLICATIONS

Survodutide is a glucagon receptor/glucagon-like peptide-1 receptor dual agonist in development for treatment of metabolic dysfunction-associated steatohepatitis (MASH), which causes cirrhosis in ∼20% of cases. This trial delineates the pharmacokinetic and safety profile of survodutide in people with compensated or decompensated cirrhosis, and revealed associated reductions in liver fat content, markers of liver fibrosis and body weight. These findings have potential relevance for people with MASH-including those with decompensated cirrhosis, who are usually excluded from clinical trials of investigational drugs. Based on this study, further investigation of survodutide for MASH-related cirrhosis is warranted.

Informations de copyright

Copyright © 2024. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest EL reports research/grant support from 89bio, Allergan, Akero Therapeutics, AstraZeneca, Axcella Health, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Durect, Eli Lilly and Company, Elobix, Enanta Pharmaceuticals, Enyo, Galmed Pharmaceuticals, Genfit, Gilead Sciences, Hanmi Pharmaceuticals, Intercept Pharmaceuticals, Laboratory for Advanced Medicine, Madrigal Pharmaceuticals, Merck, Metacrine, Novartis, Novo Nordisk, Octeta Therapeutics, Poxel, Roche Pharmaceuticals, Viking and Zydus. GWN reports disclosures for Boehringer Ingelheim and Intercept Pharmaceuticals, Inc. JMS reports consultancy fees from Akero, 89Bio, Boehringer Ingelheim, Ipsen, Inventiva Pharma, Madrigal, Northsea Therapeutics, Novo Nordisk, Roche, Siemens Healthineers; research funding from Boehringer Ingelheim. Stock Options: AGED diagnostics, Hepta Bio. Speaker Honorarium: Novo Nordisk, Madrigal, MedPublico GmbH. MN reports disclosures for Houston Methodist, Houston Research Institute, and stock options for Rivus Pharma, CIMA, Cytodyn, and ChronWell. NA reports grant/research support from 89Bio, Akero, Arbutus, Better Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Corcept, DSM, Galectin, Genentech, Genfit, Gilead, Hepagene, Healio, Intercept, Inventiva, Ionis, Madrigal, Merck, NGM, Noom, NorthSea, Novo Nordisk, Perspectum, Pfizer, Poxel, Viking, and Zydus; speaker’s fees from AbbVie, Alexion, Echosens, Eisai, Gilead, Intercept, Madrigal, Perspectum, Salix, and Theratechnologies; Consultant for 89Bio, Boehringer Ingelheim, Echosens, Fibronostics, Gilead, Intercept, Madrigal, NorthSea, Novo Nordisk, Perspectum, Pfizer, and Zydus. CPA has received consulting fees from Merck and Boehringer Ingelheim. AJS has stock options for Genfit, Exhalenz, Tiziana, Indalo, NorthSea, Durect, HemoShear, and Rivus. He has been a consultant for Intercept Pharmaceuticals, Inc., AstraZeneca, Amgen, Salix, Janssen, Gilead, Mallinckrodt, Terns, Merck, Siemens, 89Bio, NGM Bio, Poxel, Boehringer Ingelheim, Eli Lilly, HemoShear, Bristol Myers Squibb, Novartis, Novo Nordisk, Pfizer, Albireo, Regeneron, Genentech, Alnylam, Roche, Madrigal, Inventiva, Covance, ProSciento, HistoIndex, PathAI, and Genfit. He has received research grant support to Virginia Commonwealth University from Intercept Pharmaceuticals, Inc., Gilead, Bristol Myers Squibb, Eli Lilly, Merck, Boehringer Ingelheim, Novo Nordisk, Fractyl, Mallinckrodt, Madrigal, Inventiva, Novartis, and Pfizer. He receives royalties from Elsevier and UpToDate. MF, BS, SAH, AH-T, DFM, and RY are employees of Boehringer Ingelheim. The remaining authors have no conflicts to report.