Bioarctic Ab Class B · OMXSTO:BIOA_B
Bioarctic Ab Class B — Technical Presentation (August 2022)
9 slides from Bioarctic Ab Class B's technical presentation, Aug 4, 2022
Slide 1: Modeled Impact of APOE4 Genotype on ARIA-E Incidence in Patients Treated With Lecanemab
Modeled Impact of APOE4 Genotype on ARIA-E Incidence in Patients Treated With Lecanemab Larisa Reyderman,1 Seiichi Hayato,2 Harsha Reddy,1 Osamu Takenaka,1 Sanae Yasuda,2 Chad J. Swanson,1 Brian A. Willis,1 and Ziad Hussein3 1. Eisai Inc., Woodcliff Lake, NJ, USA 2. Eisai Co., Ltd., Tokyo, Japan 3.
Slide 2: Presenter Disclosures
Presenter Disclosures • Dr Reyderman is an employee of Eisai. 2
Slide 3: Lecanemab: Anti-Aβ Protofibril Monoclonal Antibody
Lecanemab: Anti-Aβ Protofibril Monoclonal Antibody Selectively Targets Aβ Protofibrils Lecanemab • Humanized immunoglobulin G1 (IgG1) monoclonal Binding Affinity antibody • Selectively binds to soluble Aβ aggregate species Monomer Oligomer Protofibrils Fibril – >1000-fold selectivity for protofibril
Slide 4: ARIA-E Exposure-Response Analysis
ARIA-E Exposure-Response Analysis Effect of APOE4 Carrier Status • Estimated baseline hazard was 26% lower for • Population PK model was used to derive APOE4 non-carriers than carriers Cmax,ss and Cave,ss for sequential • ARIA-E best correlated with Cmax at steady-state Exposure-Response analysis of
Slide 5: Analysis Objectives
Analysis Objectives • To evaluate APOE4 genotype defined as APOE4 homozygous carrier, heterozygous carrier, and APOE4 non-carrier as a covariate in the exposure-ARIA-E model • To evaluate lecanemab exposure parameter (Css,max or Css,ave) that is best predictor of ARIA-E incidence • To test hypothesi
Slide 6: ARIA-E Exposure-Response Model: Exposure Parameters and APOE4 Genotype Covariate Evaluation
ARIA-E Exposure-Response Model : Exposure Parameters and APOE4 Genotype Covariate Evaluation • Inclusion of APOE4 genotype as a covariate Model in the model with 3 categories led to a Model Description OFV* # statistically significant decrease in model 1 Css,max without covariates 345.597 objective
Slide 7: ARIA-E Exposure-Response Model Predictions
ARIA-E Exposure-Response Model Predictions • Model-predicted ARIA-E rates for APOE4 homozygous carriers Model Predicted and Observed treated with lecanemab 10 mg/kg biweekly were 22.5% (versus 6.8% ARIA-E vs. Cmax in heterozygous or 5.4% in noncarriers) – Comparable to the observed 25% incidence in
Slide 8: Summary and Conclusions
Summary and Conclusions • APOE4 genotype is a significant covariate in the exposure-ARIA-E model • The probability of ARIA-E was best correlated with lecanemab maximum concentration at steady-state (Css,max) • ARIA-E incidence is higher in APOE4 homozygous carriers and lower and similar in APOE4 non
Slide 9: Acknowledgments
Acknowledgments We thank the participants, their families and study partners, and the sites and staff participating in this study for their significant contributions Funding for the studies and analyses was provided by Eisai Inc. and Biogen Inc. Editorial support, funded by Eisai Inc, was provided b