AKR-001, an Fc-FGF21 Analog, Showed Sustained Pharmacodynamic Effects on Insulin Sensitivity and Lipid Metabolism in Type 2 Diabetes Patients
Summary: 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-pharmacolo...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-07-01
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| Series: | Cell Reports Medicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666379120300732 |
| _version_ | 1819205169370365952 |
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| author | Allegra Kaufman Lubna Abuqayyas William S. Denney Erik J. Tillman Tim Rolph |
| author_facet | Allegra Kaufman Lubna Abuqayyas William S. Denney Erik J. Tillman Tim Rolph |
| author_sort | Allegra Kaufman |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-12-23T04:47:26Z |
| format | Article |
| id | doaj.art-ff70adc410394e34a7243a26c6816dac |
| institution | Directory Open Access Journal |
| issn | 2666-3791 |
| language | English |
| last_indexed | 2024-12-23T04:47:26Z |
| publishDate | 2020-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports Medicine |
| spelling | doaj.art-ff70adc410394e34a7243a26c6816dac2022-12-21T17:59:36ZengElsevierCell Reports Medicine2666-37912020-07-0114100057AKR-001, an Fc-FGF21 Analog, Showed Sustained Pharmacodynamic Effects on Insulin Sensitivity and Lipid Metabolism in Type 2 Diabetes PatientsAllegra Kaufman0Lubna Abuqayyas1William S. Denney2Erik J. Tillman3Tim Rolph4Amgen Inc., Thousand Oaks, CA 91320, USAAmgen Inc., Thousand Oaks, CA 91320, USAHuman Predictions, LLC, Cambridge, MA 02139, USAAkero Therapeutics, South San Francisco, CA 94080, USAAkero Therapeutics, South San Francisco, CA 94080, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2666379120300732 |
| spellingShingle | Allegra Kaufman Lubna Abuqayyas William S. Denney Erik J. Tillman Tim Rolph AKR-001, an Fc-FGF21 Analog, Showed Sustained Pharmacodynamic Effects on Insulin Sensitivity and Lipid Metabolism in Type 2 Diabetes Patients Cell Reports Medicine |
| 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 |
| url | http://www.sciencedirect.com/science/article/pii/S2666379120300732 |
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