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Model-based comparisons of post-treatment free IgE and FEV1 between omalizumab asthma dosing tables in the United States and European Union
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  • Rui Zhu,
  • Rik Schoemaker,
  • Aurelie Gautier,
  • Xianbin Tian,
  • Cheryl Sim,
  • Theodore Omachi,
  • Joshi Amita,
  • Jin Jin,
  • Ryan Owen
Rui Zhu
Genentech Inc
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Rik Schoemaker
Occams/Leiden University
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Aurelie Gautier
Novartis Pharma AG
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Xianbin Tian
Novartis Pharmaceuticals Corporation
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Cheryl Sim
Genentech Inc
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Theodore Omachi
Genentech Inc
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Joshi Amita
Genentech Inc
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Jin Jin
Genentech Inc
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Ryan Owen
Genentech Inc

Corresponding Author:[email protected]

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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.
06 Apr 2024Submitted to British Journal of Clinical Pharmacology
08 Apr 2024Submission Checks Completed
08 Apr 2024Assigned to Editor
08 Apr 2024Review(s) Completed, Editorial Evaluation Pending
09 Apr 2024Reviewer(s) Assigned
24 Jun 20241st Revision Received
26 Jun 2024Review(s) Completed, Editorial Evaluation Pending
10 Jul 2024Editorial Decision: Accept