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The AAPS Journal

, 21:9 | Cite as

Measurement of IL-17AA and IL-17FF as Pharmacodynamic Biomarkers to Demonstrate Target Engagement in the Phase I Study of MCAF5352A

  • Kun PengEmail author
  • Yehong Wang
  • Ketevan Siradze
  • Rich Erickson
  • Saloumeh K. Fischer
  • Tracy L. Staton
Research Article
  • 160 Downloads

Abstract

The interleukin (IL)-17 pathway has been implicated in the pathophysiology of many autoimmune diseases. MCAF5352A is a humanized monoclonal antibody which targets both IL-17A and IL-17F, thereby inhibiting the activity of IL-17 dimers (IL-17AA, IL-17AF, and IL-17FF). The pharmacokinetic profile of MCAF5352A has been characterized in both a Phase Ia single ascending dose study and a Phase Ib multiple ascending dose study. Two qualified enzyme-linked immunosorbent assays were used to measure total IL-17AA and IL-17FF levels in serum as pharmacodynamic biomarkers in the Phase I studies. The two assays demonstrated specificity for IL-17AA or IL-17FF with sensitivity at low picogram/milliliter levels. The assay precision and accuracy also met acceptance criteria. Although total serum IL-17AA and IL-17FF levels were below the assay detection limits prior to administration of MCAF5352A, post-treatment levels in both the single and multiple dose cohorts became detectable and increased in a dose-dependent manner. These data are consistent with target engagement by MCAF5352A. Our work highlights bioanalytical challenges encountered while developing biomarker assays requiring high sensitivity and specificity. Data generated using these assays enabled the confirmation of target engagement during early clinical drug development.

KEY WORDS

anti-IL-17 monoclonal antibody biomarker assay IL-17AA IL-17FF pharmacodynamics 

Notes

Acknowledgements

MCAF5352A is a molecule in-licensed from Novimmune SA.

Funding Details

This study was funded by Genentech Inc., South San Francisco, CA, USA.

Compliance with Ethical Standards

Conflict of Interest

All authors are Genentech employees and Roche shareholders.

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Kun Peng
    • 1
    Email author
  • Yehong Wang
    • 2
  • Ketevan Siradze
    • 1
  • Rich Erickson
    • 1
  • Saloumeh K. Fischer
    • 1
  • Tracy L. Staton
    • 3
  1. 1.Department of BioAnalytical SciencesGenentech IncSouth San FranciscoUSA
  2. 2.Department of Clinical PharmacologyGenentech IncSouth San FranciscoUSA
  3. 3.Department of OMNI Biomarker DevelopmentGenentech IncSouth San FranciscoUSA

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