Model-based comparisons of post-treatment free IgE and FEV1 between
omalizumab asthma dosing tables in the United States and European Union
Abstract
Aims: 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
modeling and simulation approaches to predict and compare the free IgE
reduction and forced expiratory volume in 1 second (FEV1) improvement
with omalizumab dosing based on the US and EU asthma dosing tables.
Methods: 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. Results/Conclusions: The US and EU asthma dosing tables
were predicted to result in generally comparable free IgE suppression
and FEV1 improvement. However, this has not been clinically validated
with respect to the registrational endpoint of reduction in annualized
asthma exacerbations.