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Volume 6, Issue 6(Suppl) J Clin Toxicol 2016
ISSN: 2161-0495, JCT an open access journal
Page 92
Notes:
Euro Toxicology 2016
October 24-26, 2016
conferenceseries.com
Toxicology & Applied Pharmacology
October 24-26, 2016 Rome, Italy
7th Euro-Global Summit on
A new pegylated recombinant E.coli L-asparaginase preparation (MC0609): Comparative
pharmacokinetic/pharmacodynamic characterisation in Beagle dog and influence of anti-PEG
IgM antibodies on the pharmacokinetics in B6D2F1 mice
Poppenborg Sabine M
Medac GmbH, Germany
Anew pegylated recombinant E. coli L-asparaginase (PEG-rASNase MC0609) was designed by medac GmbH (Germany)
to improve pharmacokinetic (PK) characteristics of pegylated L-asparaginase in comparison to pegaspargase (Oncaspar®)
used as first-line treatment in patients with acute lymphoblastic leukaemia (ALL). Comparative PK, pharmacodynamic (PD)
and immunogenicity studies were performed in Beagle dogs after single-dose intravenous (i.v.) administration of MC0609 or
pegaspargase. Striking differences in PK and PD properties between both pegylated preparations were observed. The different
PK characteristics were confirmed by a population pharmacokinetic (PopPK) analysis. PK parameters of pegaspargase in
Beagle dog were in the same range than the parameters determined in paediatric ALL patients. Therefore, the Beagle dog was
considered a clinically relevant model for PK evaluation of pegaspargase. In addition, the potential impact of pre-existing anti-
PEG antibodies on the ASNase activity of PEG-rASNase MC0609 and pegaspargase was investigated in immune competent
B6D2F1-hybrid mice. Anti-PEG IgM antibodies were successfully induced in mice after repeated i.v. administration of 40
kDa PEG-Diol without being conjugated to a carrier. All animals detected “positive” for anti-PEG IgM antibodies and control
animals (without prior PEG-Diol pre-sensitisation) were treated once i.v. with PEG-rASNase MC0609 or pegaspargase. ASNase
activity profiles were obviously not influenced by the IgM positivity of animals. No accelerated decrease of ASNase activity was
observed irrespective of successful PEG-Diol pre-sensitisation and presence of acquired anti-drug-IgG and/or anti-PEG IgM
antibodies.
Biography
Poppenborg Sabine M has completed her PhD from University of Bielefeld, Germany, University of Montpellier, France and Post-doctoral studies from MRC Medical
Research Council, Cambridge, UK. Since 2007, she is a Scientist in the Pharmacology/Toxicology unit of medac Gesellschaft für klinische Spezialpräparate mbH,
Germany, a pharmaceutical company specialised on products for oncology, autoimmune diseases and urology.
Poppenborg Sabine M, J Clin Toxicol 2016, 6:6(Suppl)