AB1212 Analytical validation of an interferon-inducible gene expression kit as a potential diagnostic test for anifrolumab

Background Anifrolumab, a fully human monoclonal antibody that binds to the type I interferon receptor, is in Phase III development for moderate to severe systemic lupus erythematosus (SLE). Patients with greater interferon-inducible gene signatures (IFNGS) have enhanced response to anifrolumab treatment. 1 AstraZeneca and QIAGEN developed an in-vitro diagnostic test for interferon-inducible gene expression (IFIGx). Efficacy of anifrolumab will be evaluated in patients with high and low IFNGS. Objectives We aimed to analytically validate the IFIGx kit for use in a pivotal clinical study and potentially to support future regulatory submission. Methods The IFIGx kit measures expression of four interferon-inducible genes (IF127, IF114, IF114L and RSAD2) compared with three housekeeping genes. Measurements were performed on mRNA extracted from whole blood from adults with SLE. A score was generated that identified patients as “IFNGS test–high” or “IFNGS test–low.” Analytical validation involved six studies measuring lot interchangeability, linearity, repeatability, reproducibility, cross contamination, and system verification. Results Repeatability was 100%. Reproducibility was >96%. No cross contamination was observed. Results of all studies validated the IFIGx kit (table 1). Conclusions The IFIGx kit was shown to be a robust, reproducible diagnostic test for IFNGS. The IFIGx kit has demonstrated value in prior anifrolumab studies, 1 and will be used both for patient stratification in Phase III studies and to support anifrolumab regulatory filings. Reference [1] Furie, et al. Arthritis Rheumatol . 2017;69:376–86. Disclosure of Interest P. Brohawn Employee of: MedImmune LLC, B. Higgs Employee of: MedImmune LLC, S. Patel Employee of: AstraZeneca, A. Moody Employee of: QIAGEN Manchester Ltd, P. Cooper Employee of: QIAGEN Manchester Ltd, K. Ranade Employee of: MedImmune LLC