Journal
CLINICAL PHARMACOLOGY & THERAPEUTICS
Volume 89, Issue 2, Pages 283-290Publisher
WILEY
DOI: 10.1038/clpt.2010.311
Keywords
-
Categories
Funding
- Genentech Research and Early Development, of the Roche Group
Ask authors/readers for more resources
MTRX1011A is a humanized anti-CD4 antibody with an amino acid substitution (N434H) to improve its binding to the neonatal Fc receptor (FcRn). Pharmacokinetic/pharmacodynamic (PK/PD) data in baboons suggest that the increased binding to FcRn reduces the nonspecific elimination rate (K-el) of MTRX1011A by similar to 50% but does not affect its PK-PD relationship. The human PK/PD data of MTRX1011A from a phase I study in patients with rheumatoid arthritis (RA) were compared with those previously reported for TRX1, its predecessor antibody, using population PK-PD modeling. The results suggest a comparable PK-PD relationship and no significant difference between the K-el values of the two antibodies. However, the results may have been confounded by the differences in the clinical populations in which the two antibodies were studied and the presence of preexisting immunoglobulin M (IgM) antibodies in the RA sera that recognize N434H in MTRX1011A. This study highlights the challenges in translating from animal studies to human application the effects of FcRn-directed mutations on the PK of monoclonal antibodies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available