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AKR-001, an Fc-FGF21 Analog, Showed Sustained Pharmacodynamic Effects on Insulin Sensitivity and Lipid Metabolism in Type 2 Diabetes Patients

Experimental fibroblast growth factor 21 (FGF21) analogs can improve lipid profiles in patients with metabolic diseases. However, their effects on markers of insulin sensitivity appear to be minimal, potentially because of insufficient exposure. Systemic drug levels vary from sub-pharmacological to...

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Autores principales: Kaufman, Allegra, Abuqayyas, Lubna, Denney, William S., Tillman, Erik J., Rolph, Tim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659583/
https://www.ncbi.nlm.nih.gov/pubmed/33205064
http://dx.doi.org/10.1016/j.xcrm.2020.100057
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author Kaufman, Allegra
Abuqayyas, Lubna
Denney, William S.
Tillman, Erik J.
Rolph, Tim
author_facet Kaufman, Allegra
Abuqayyas, Lubna
Denney, William S.
Tillman, Erik J.
Rolph, Tim
author_sort Kaufman, Allegra
collection PubMed
description Experimental fibroblast growth factor 21 (FGF21) analogs can improve lipid profiles in patients with metabolic diseases. However, their effects on markers of insulin sensitivity appear to be minimal, potentially because of insufficient exposure. Systemic drug levels vary from sub-pharmacological to demonstrating pharmacodynamic effects but with dose-limiting adverse events. Here we report results from a phase 1 multiple ascending dose study of AKR-001, an Fc-FGF21 fusion protein engineered for sustained systemic pharmacologic exposure, in individuals with type 2 diabetes. With a half-life of 3–3.5 days, the peak-to-trough ratio under steady-state conditions is approximately 2 following QW dosing. AKR-001 appears to demonstrate pharmacodynamic effects on serum markers of insulin sensitivity and acceptable tolerability up to and including 70 mg QW. Positive trends in lipoprotein profile, including triglycerides, non-high-density lipoprotein (non-HDL) cholesterol, HDL-C, and apolipoproteins B and C3 are consistent with other FGF21 analogs. AKR-001’s clinical profile supports further evaluation as a treatment for metabolic diseases.
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spelling pubmed-76595832020-11-16 AKR-001, an Fc-FGF21 Analog, Showed Sustained Pharmacodynamic Effects on Insulin Sensitivity and Lipid Metabolism in Type 2 Diabetes Patients Kaufman, Allegra Abuqayyas, Lubna Denney, William S. Tillman, Erik J. Rolph, Tim Cell Rep Med Article Experimental fibroblast growth factor 21 (FGF21) analogs can improve lipid profiles in patients with metabolic diseases. However, their effects on markers of insulin sensitivity appear to be minimal, potentially because of insufficient exposure. Systemic drug levels vary from sub-pharmacological to demonstrating pharmacodynamic effects but with dose-limiting adverse events. Here we report results from a phase 1 multiple ascending dose study of AKR-001, an Fc-FGF21 fusion protein engineered for sustained systemic pharmacologic exposure, in individuals with type 2 diabetes. With a half-life of 3–3.5 days, the peak-to-trough ratio under steady-state conditions is approximately 2 following QW dosing. AKR-001 appears to demonstrate pharmacodynamic effects on serum markers of insulin sensitivity and acceptable tolerability up to and including 70 mg QW. Positive trends in lipoprotein profile, including triglycerides, non-high-density lipoprotein (non-HDL) cholesterol, HDL-C, and apolipoproteins B and C3 are consistent with other FGF21 analogs. AKR-001’s clinical profile supports further evaluation as a treatment for metabolic diseases. Elsevier 2020-07-21 /pmc/articles/PMC7659583/ /pubmed/33205064 http://dx.doi.org/10.1016/j.xcrm.2020.100057 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Kaufman, Allegra
Abuqayyas, Lubna
Denney, William S.
Tillman, Erik J.
Rolph, Tim
AKR-001, an Fc-FGF21 Analog, Showed Sustained Pharmacodynamic Effects on Insulin Sensitivity and Lipid Metabolism in Type 2 Diabetes Patients
title AKR-001, an Fc-FGF21 Analog, Showed Sustained Pharmacodynamic Effects on Insulin Sensitivity and Lipid Metabolism in Type 2 Diabetes Patients
title_full AKR-001, an Fc-FGF21 Analog, Showed Sustained Pharmacodynamic Effects on Insulin Sensitivity and Lipid Metabolism in Type 2 Diabetes Patients
title_fullStr AKR-001, an Fc-FGF21 Analog, Showed Sustained Pharmacodynamic Effects on Insulin Sensitivity and Lipid Metabolism in Type 2 Diabetes Patients
title_full_unstemmed AKR-001, an Fc-FGF21 Analog, Showed Sustained Pharmacodynamic Effects on Insulin Sensitivity and Lipid Metabolism in Type 2 Diabetes Patients
title_short AKR-001, an Fc-FGF21 Analog, Showed Sustained Pharmacodynamic Effects on Insulin Sensitivity and Lipid Metabolism in Type 2 Diabetes Patients
title_sort akr-001, an fc-fgf21 analog, showed sustained pharmacodynamic effects on insulin sensitivity and lipid metabolism in type 2 diabetes patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659583/
https://www.ncbi.nlm.nih.gov/pubmed/33205064
http://dx.doi.org/10.1016/j.xcrm.2020.100057
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