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Safety and Efficacy of Novel Incretin Co-agonist Cotadutide in Biopsy-proven Noncirrhotic MASH With Fibrosis.
Shankar, Sudha S; Daniels, Samuel J; Robertson, Darren; Sarv, Janeli; Sánchez, José; Carter, Debra; Jermutus, Lutz; Challis, Benjamin; Sanyal, Arun J.
Afiliación
  • Shankar SS; Early Clinical Development, Early Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland; Translational Science and Experimental Medicine, Research and Early Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, M
  • Daniels SJ; Early Clinical Development, Early Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland.
  • Robertson D; Early Clinical Development, Early Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland.
  • Sarv J; Early Biometrics & Statistical Innovation, Data Science & Artificial Intelligence, R&D, AstraZeneca, Gothenburg, Sweden.
  • Sánchez J; Early Biometrics & Statistical Innovation, Data Science & Artificial Intelligence, R&D, AstraZeneca, Gothenburg, Sweden.
  • Carter D; Global Patient Safety, Astra Zeneca, Gaithersburg, Maryland.
  • Jermutus L; Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom.
  • Challis B; Translational Science and Experimental Medicine, Research and Early Development, Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom.
  • Sanyal AJ; Division of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, Virginia.
Clin Gastroenterol Hepatol ; 22(9): 1847-1857.e11, 2024 Sep.
Article en En | MEDLINE | ID: mdl-38729399
ABSTRACT
BACKGROUND &

AIMS:

Cotadutide, a peptide co-agonist at the glucagon-like peptide-1 (GLP-1) and glucagon (GCG) receptors, has demonstrated robust improvements in body weight, glycemia, and hepatic fat fraction (HFF) in patients living with obesity and type 2 diabetes mellitus.

METHODS:

In PROXYMO, a 19-week randomized double-blind placebo-controlled trial, the safety and efficacy of cotadutide (600 µg, 300 µg) or placebo were evaluated in 74 participants with biopsy-proven noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis. Analyses were performed using intent-to-treat and modified intent-to-treat population data.

RESULTS:

Dose- and time-dependent improvements in HFF, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), markers of liver health, and metabolic parameters were observed with significant improvements after 19 weeks with 600 µg ([least squares] mean difference vs placebo, [95% confidence interval] for absolute HFF -5.0% [-8.5 to -1.5]; ALT -23.5 U/L [-47.1 to -1.8]; AST -16.8 U/L [-33.0 to -0.8]). Incidences of any grade treatment-emergent adverse events (TEAEs) were 91.7%, 76.9%, and 37.5% with cotadutide 600 µg, 300 µg, and placebo, respectively. The majority were gastrointestinal, mild to moderate in severity, and generally consistent with other incretins at this stage of development. TEAEs leading to treatment discontinuation were 16.7%, 7.7%, and 4.2% with cotadutide 600 µg, 300 µg, and placebo, respectively.

CONCLUSIONS:

PROXYMO provides preliminary evidence for the safety and efficacy of GLP-1/GCG receptor co-agonism in biopsy-proven noncirrhotic MASH with fibrosis, supporting further evaluation of this mechanism in MASH. CLINICAL TRIAL REGISTRATION NUMBER NCT04019561.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Incretinas Idioma: En Revista: Clin Gastroenterol Hepatol Asunto de la revista: GASTROENTEROLOGIA Año: 2024 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Incretinas Idioma: En Revista: Clin Gastroenterol Hepatol Asunto de la revista: GASTROENTEROLOGIA Año: 2024 Tipo del documento: Article