Nonclinical Evaluation of PF-06438179: A Potential Biosimilar to Remicade® (Infliximab)
| العنوان: | Nonclinical Evaluation of PF-06438179: A Potential Biosimilar to Remicade® (Infliximab) |
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| المؤلفون: | Leslie G. Lorello, Jim McNally, Hugh D. Conlon, Michael W. Leach, Carol F. Kirchhoff, Teresa Annette Smolarek, Andrew Saati, Sarah Koob, Mazin Derzi, Ahmed M. Shoieb, Penny Sharpe, Michael W. Bolt, Theodore R. Johnson |
| المصدر: | Advances in Therapy |
| بيانات النشر: | Springer Science and Business Media LLC, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Monoclonal antibody, Male, 0301 basic medicine, Tumor necrosis factor, medicine.drug_class, Pharmacology toxicology, Drug Evaluation, Preclinical, Remicade, Pharmacology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, medicine, Animals, Pharmacology (medical), Biosimilar Pharmaceuticals, Original Research, Medicine(all), 030203 arthritis & rheumatology, Toxicity, Tumor Necrosis Factor-alpha, business.industry, Biosimilar, Antibodies, Monoclonal, General Medicine, Infliximab, Toxicokinetics, Rats, Human tumor, Treatment Outcome, 030104 developmental biology, Liver, Immunology, Administration, Intravenous, Tumor necrosis factor alpha, business, Immunosuppressive Agents, medicine.drug |
| الوصف: | Introduction PF-06438179, a potential biosimilar to Remicade® (infliximab, Janssen Biotech, Inc.), is a chimeric mouse–human monoclonal antibody targeting human tumor necrosis factor alpha (TNF). Methods Analytical (small subset reported here) and nonclinical studies compared the structural, functional, and in vivo nonclinical similarity of PF-06438179 with Remicade sourced from the United States (infliximab-US) and/or European Union (infliximab-EU). Results The peptide map profiles were superimposable, and peptide masses were the same, indicating identical amino acid sequences. Data on post-translational modifications, biochemical properties, and biological function provided strong support for analytical similarity. Administration of a single intravenous (IV) dose (10 or 50 mg/kg) of PF-06438179 or infliximab-EU to male rats was well tolerated. There were no test article-related clinical signs or effects on body weight or food consumption. Systemic exposures [maximum drug concentration (C max) and area under the concentration–time curve (AUC)] in rats administered PF-06438179 or infliximab-EU were similar, with mean exposure ratio of PF-06438179 relative to infliximab-EU ranging from 0.88 to 1.16. No rats developed anti-drug antibodies. A 2-week IV toxicity study was conducted with once-weekly administration of 10 or 50 mg/kg of PF-06438179 to male and female rats. PF-06438179-related hyperplasia of sinusoidal cells occurred in the liver in rats administered 50 mg/kg, but was not adverse based on its minimal to mild severity. The no-observed adverse-effect level for PF-06438179 was 50 mg/kg. At this dose, C max was 1360 µg/mL and AUC at 168 h was 115,000 µg h/mL on day 8. Conclusions The analytical and nonclinical studies have supported advancement of PF-06438179 into global comparative clinical trials. Funding Pfizer Inc. |
| تدمد: | 1865-8652 0741-238X |
| DOI: | 10.1007/s12325-016-0403-9 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::af1eb4ef54c3121972985f519b27fd07 https://doi.org/10.1007/s12325-016-0403-9 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....af1eb4ef54c3121972985f519b27fd07 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18658652 0741238X |
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| DOI: | 10.1007/s12325-016-0403-9 |