Model-based comparisons of post-treatment free IgE and FEV1 between omalizumab asthma dosing tables in the United States and European Union.

Abstract

Omalizumab is an anti-immunoglobulin E (IgE) monoclonal antibody that was first approved by the United States (US) Food and Drug Administration (FDA) for the treatment of allergic asthma in 2003. The pivotal trials supporting the initial approval of omalizumab used dosing determined by patient's baseline IgE and body weight, with the goal of reducing the mean free IgE level to approximately 25 ng/mL or less. While the underlying parameters supporting the dosing table remained the same, subsequent studies and analyses have resulted in approved alternative versions of the dosing table, including the European Union (EU) asthma dosing table, which differs in weight bands and maximum allowable baseline IgE and omalizumab dose. In this study, we leveraged modelling and simulation approaches to predict and compare the free IgE reduction and forced expiratory volume in 1second (FEV1) improvement with omalizumab dosing based on the US and EU asthma dosing tables. Previously established population pharmacokinetic-IgE and IgE-FEV1 models were used to predict and compare post-treatment free IgE and FEV1 based on the US and EU dosing tables. Clinical trial simulations (with virtual asthma populations) and Monte Carlo simulations were performed to provide both breadth and depth in the comparisons. The US and EU asthma dosing tables were predicted to result in generally comparable free IgE suppression and FEV1 improvement. Despite the similar free IgE and FEV1 outcomes from simulations, this has not been clinically validated with respect to the registrational endpoint of reduction in annualized asthma exacerbations.