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Updated: May 13, 2026

Development and Validation of an Ultrasensitive Single Molecule Array Digital Enzyme-linked Immunosorbent Assay for Human Interferon-α
08:26

Development and Validation of an Ultrasensitive Single Molecule Array Digital Enzyme-linked Immunosorbent Assay for Human Interferon-α

Published on: June 14, 2018

Pharmacogenomics and translational simulations to bridge indications for an anti-interferon-α receptor antibody

B Wang1, B W Higgs, L Chang

  • 1Department of Translational Sciences, MedImmune, LLC, Gaithersburg, Maryland, USA.

Clinical Pharmacology and Therapeutics
|March 21, 2013
PubMed

A type I interferon (IFN) gene signature shared by systemic lupus erythematous (SLE) and systemic sclerosis (SSc) was used to evaluate an anti-type I IFN-α receptor (IFN-αR) monoclonal antibody, MEDI-546, in a phase I trial in SSc. MEDI-546 suppressed IFN signature in blood and skin of SSc patients in a dose-dependent manner. To bridge clinical indications to SLE, we developed a model incorporating (i) pharmacokinetics (PK) and pharmacodynamics (PD) in SSc patients, (ii) internalization kinetics of MEDI-546/IFN-αR complex, and (iii) the different IFN signatures between SSc and SLE. Simulations predicted that i.v. administration of MEDI-546 at 300- or 1,000-mg monthly doses could suppress IFN signature in blood to levels of healthy subjects in 53 and 68% of SLE patients, respectively. An innovative approach utilizing a novel biomarker characterized the PD of MEDI-546 by modeling and simulation and allowed rapid progression of MEDI-546 from a phase I study in SSc to a randomized, multiple-dose phase II trial.

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