A Novel Investigational Fc-Modified Humanized Monoclonal Antibody, Motavizumab-YTE, Has an Extended Half-Life in Healthy Adults
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The study objective was to evaluate the pharmacokinetics (PK), antidrug antibody (ADA), and safety of motavizumab-YTE (motavizumab with amino acid substitutions M252Y/S254T/T256E [YTE]), an Fc-modified anti-respiratory syncytial virus (RSV) monoclonal antibody. Healthy adults ( n = 31) were randomized to receive a single intravenous (i.v.) dose of motavizumab-YTE or motavizumab (0.3, 3, 15, or 30 mg/kg) and followed for 240 days. Clearance of motavizumab-YTE was significantly lower (71% to 86%) and the half-life ( t 1/2 ) was 2- to 4-fold longer than with motavizumab. However, similar peak concentrations and volume-of-distribution values, indicative of similar distribution properties, were seen at all dose levels. The sustained serum concentrations of motavizumab-YTE were fully functional, as shown by RSV neutralizing activity that persisted for 240 days with motavizumab-YTE versus 90 days postdose for motavizumab. Safety and incidence of ADA were comparable between groups. In this first study of an Fc-modified monoclonal antibody in humans, motavizumab-YTE was well tolerated and exhibited an extended half-life of up to 100 days. (This study has been registered at ClinicalTrials.gov under registration no. NCT00578682.)
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Improved understanding of the IgG-FcRn interaction along with advances in protein engineering has led to opportunities to engineer mAbs with extended half-life.
“Improved understanding of the IgG‐FcRn interaction along with advances in protein engineering has led to opportunities to engineer mAbs with extended half‐life.32”
From Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development (2018) · cites this paper as [32]
M252Y/S254T/T256E (YTE) mutations on motavizumab led to a 10-fold increase in affinity for human FcRn at pH 6.0 with no change in affinity at pH 7.4 and significantly increased its half-life in monkeys and in healthy adult humans.
“M252Y/S254T/T256E (YTE) mutations on motavizumab led to a 10‐fold increase in affinity for human FcRn at pH 6.0 with no change in affinity at pH 7.4 and significantly increased its half‐life in monkeys and in healthy adult humans.32”
From Tutorial on monoclonal antibody pharmacokinetics and its considerations in early development (2018) · cites this paper as [32]
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- Authors
- Robbie, G. J., Criste, R., Dall'Acqua, W. F., Jensen, K., Patel, N. K., Losonsky, G. A., & Griffin, M. P.
- Affiliations
- Clinical Pharmacology and DMPK, MedImmune, Gaithersburg, Maryland, USA
- Antibody Discovery and Protein Engineering, MedImmune, Gaithersburg, Maryland, USA
- Biostatistics, MedImmune, Gaithersburg, Maryland, USA
- Research and Development, Infectious Disease, MedImmune, Gaithersburg, Maryland, USA
- Clinical Research and Development, MedImmune, Gaithersburg, Maryland, USA
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2013-12
- Volume
- 57
- Issue
- 12
- Pages
- 6147-6153
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC3837853
- OpenAlex
- W2148090354
- Cited by
- 366
- References
- 18
- Citations by year
- 2026: 31 · 2025: 26 · 2024: 33 · 2023: 37 · 2022: 47 · 2021: 22 · 2020: 20 · 2019: 26 · 2018: 26 · 2017: 38 · 2016: 19 · 2015: 25 · 2014: 14 · 2013: 1
- FWCI
- 15.26
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Keywords
- respiratory syncytial virus, pharmacokinetics, extended half-life, clearance, amino acid substitutions, antidrug antibodies, drug safety, healthy volunteers
- MeSH terms
- Adult, Antiviral Agents, Double-Blind Method, Female, Half-Life, Humans, Immunoglobulin Fc Fragments, Injections, Intravenous, Male, Metabolic Clearance Rate, Drugs, Investigational, Antibodies, Monoclonal, Humanized
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