title: An ex vivo potency assay to assess active drug levels of a GLP-1 agonistic peptide during preclinical safety studies.
abstract: BACKGROUND
  During development of biologics, safety and efficacy assessments are often hampered by immune responses to the treatment. To assess active exposure of a drug peptide in a toxicology study, we developed an ex vivo potency assay which complemented the total drug quantification assay.
  
  
  METHODS
  Compound activity was assessed in samples of treated monkeys by cell-based cAMP measurements. For each animal, activity was compared with its predose sample to which the compound has been added at the postdose concentration as determined by a total LC-MS/MS assay.
  
  
  CONCLUSIONS
  We were able to show that despite a high total test compound level, activity was reduced tremendously in antidrug-antibody-positive monkeys. Therefore, the applied ex vivo potency assay supplements drug quantification methods to determine active exposures.
authors.affiliation: Roche Pharmaceutical Research & Early Development, Pharmaceutical Sciences, Roche Innovation Center Penzberg, Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schäfer
authors.affiliation: Roche Pharmaceutical Research & Early Development, Pharmaceutical Sciences, Roche Innovation Center Penzberg, Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: Steven
authors.initials: S
authors.lastname: Challand
authors.affiliation: Roche Pharmaceutical Research & Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors.forename: Eginhard
authors.initials: E
authors.lastname: Schick
authors.affiliation: Roche Pharmaceutical Research & Early Development, Pharmaceutical Sciences, Roche Innovation Center Penzberg, Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Bader
authors.affiliation: Metabolism & Pharmacokinetics, Novartis Institute for BioMedical Research, 250 Massachusetts Ave, Cambridge, MA 02139, USA.
authors.forename: Dominik
authors.initials: D
authors.lastname: Hainzl
authors.affiliation: Roche Pharmaceutical Research & Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors.forename: Katja
authors.initials: K
authors.lastname: Heinig
authors.affiliation: Roche Pharmaceutical Research & Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors.forename: Lutz
authors.initials: L
authors.lastname: Müller
authors.affiliation: Roche Pharmaceutical Research & Early Development, Pharmaceutical Sciences, Roche Innovation Center Penzberg, Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: Apollon
authors.initials: A
authors.lastname: Papadimitriou
authors.affiliation: Roche Pharmaceutical Research & Early Development, Pharmaceutical Sciences, Roche Innovation Center Penzberg, Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Heinrich
mesh_terms: D000818:Animals; D001681:Biological Assay / Q000379:methods*; D002853:Chromatography, Liquid / Q000379:methods*; D000242:Cyclic AMP / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D008252:Macaca fascicularis; D008297:Male; D010446:Peptide Fragments / Q000097:blood* / Q000494:pharmacology; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D010446:Peptide Fragments; D052216:Glucagon-Like Peptide 1; D000242:Cyclic AMP