Nonclinical pharmacology and toxicology of the first biosimilar insulin glargine drug product (BASAGLAR ® /ABASAGLAR ® ) approved in the European Union
| Autor: | Jamie L. Blackbourne, David E. Coutant, Julie S. Moyers, Owens Rebecca Anne, M. Dodson Michael, Richard A. Byrd, A. Eric Schultze, John L. Vahle, Michael K. Sievert, Niraj Tripathi, Mark W. Farmen |
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| Rok vydání: | 2017 |
| Předmět: |
medicine.medical_specialty
Insulin glargine business.industry Insulin medicine.medical_treatment 030209 endocrinology & metabolism Biosimilar General Medicine 030204 cardiovascular system & hematology Pharmacology Toxicology Reference drug 03 medical and health sciences 0302 clinical medicine Endocrinology Pharmacokinetics Internal medicine medicine Drug product media_common.cataloged_instance Dosing European union business medicine.drug media_common |
| Zdroj: | Regulatory Toxicology and Pharmacology. 88:56-65 |
| ISSN: | 0273-2300 |
| DOI: | 10.1016/j.yrtph.2017.05.013 |
| Popis: | Basaglar®/Abasaglar® (Lilly insulin glargine [LY IGlar]) is a long-acting human insulin analogue drug product granted marketing authorisation as a biosimilar to Lantus® (Sanofi insulin glargine [SA IGlar]) by the European Medicines Agency. We assessed the similarity of LY IGlar to the reference drug product, European Union–sourced SA IGlar (EU-SA IGlar), using nonclinical in vitro and in vivo studies. No biologically relevant differences were observed for receptor binding affinity at either the insulin or insulin-like growth factor-1 (IGF-1) receptors, or in assays of functional or de novo lipogenic activity. The mitogenic potential of LY IGlar and EU-SA IGlar was similar when tested in both insulin- and IGF-1 receptor dominant cell systems. Repeated subcutaneous daily dosing of rats for 4 weeks with 0, 0.3, 1.0, or 2.0 mg/kg LY IGlar and EU-SA IGlar produced mortalities and clinical signs consistent with severe hypoglycaemia. Glucodynamic profiles of LY IGlar and EU-SA IGlar in satellite animals showed comparable dose-related hypoglycaemia. Severe hypoglycaemia was associated with axonal degeneration of the sciatic nerve; the incidence and severity were low and did not differ between LY IGlar and EU-SA IGlar. These results demonstrated no biologically relevant differences in toxicity between LY IGlar and EU-SA IGlar. |
| Databáze: | OpenAIRE |
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