QGE031 (ligelizumab) is more effective than omalizumab and placebo in inhibiting allergen-induced early asthmatic response: Results from a predictive modeling study

Aim: QGE031 is a high-affinity humanized anti-IgE antibody in development for treatment of uncontrolled severe asthma. We predicted steady-state dose responses by fitting a mathematical model to PKPD data. Methods: Subjects with mild, atopic asthma (N=37) were randomised to 3 s.c. doses (240mg,N=8; 72mg,N=8; 24mg,N=8) of QGE031 every 2 weeks (wks) for 12wks, Omalizumab (OMA) (N=6; US dosing table) or placebo (N=7). Allergen challenges were conducted 6, 12 and 18 wks after the first dose. Mathematical functions were fitted to full time course drug, total IgE and basophil data. After curve fitting, 0-6 month responses of ∼1000 patients, each receiving an array of 4 wkly administrations of QGE031 (0-1200mg) and OMA (US dosing table), were simulated. Results: The model fitted the response data, down regulation of basophil FceR1 and surface IgE, and inhibition of bronchial and skin allergen reactivity from subjects treated with QGE031 and OMA. QGE031 36mg, dosed every 4 wks, was predicted to give similar skin wheal and allergen PC15 responses to OMA. Higher doses of QGE031 would be required for patients with higher baseline IgE. Conclusion: QGE031 is more effective than OMA in inhibiting bronchial and skin allergen response in a clinical setting. This mathematical model could allow better planning and prediction of future trial outcomes.