Phil Lowe

Pharmacokinetics, pharmacodynamics and safety of QGE031 (ligelizumab), a novel high-affinity anti-IgE antibody, in atopic subjects

Using a monoclonal antibody with greater affinity for IgE than omalizumab, we examined whether more complete suppression of IgE provided greater pharmacodynamic effects, including suppression of skin prick responses to allergen.

Population Modeling of Filgrastim PK‐PD in Healthy Adults Following Intravenous and Subcutaneous Administrations

Filgrastim is a recombinant human granulocyte colony stimulating factor (G‐CSF) that stimulates production of neutrophils. The objective of this analysis was to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model to account for an increase in G‐CSF clearance on multiple dosing because of an increase of the G‐CSF receptor‐mediated endocytosis. Data from 4 randomized studies involving healthy volunteers were used for analysis. Subjects received filgrastim (Neupogen) via subcutaneous (SC) and intravenous (IV) routes. Filgrastim was administered SC daily for 1 week at 2.5, 5, and 10 μg/kg doses and as single IV infusions (5 μg/kg over 0.5 hours) and SC (1 μg/kg) doses. PK data comprised serum concentration‐time measurements and the blood absolute neutrophil count (ANC) was used for PD evaluations. Population nonlinear mixed‐effect modeling was done using NONMEM VI (Version 6.1.0, Icon Development Solutions, Ellicott City, Maryland). The model depicted the decaying trend in Cmax values with repeated doses and an increase in ANCmax values consistently with an increase in the G‐CSF receptor pool. Simulated time courses of the total clearance exhibited an increasing pattern. The increase in filgrastim clearance on multiple dosing was attributed to the increased neutrophil count in the bone marrow and blood paralleled by an increase in the total G‐CSF receptor density.

P02-026 - Model-based characterization of the PKPD relationship for canakinumab in CAPS: a step towards personalized

Canakinumab is a high-affinity fully human monoclonal antibody of the IgG1/k isotype, designed to bind and functionally neutralize the bioactivity of IL-1β, which is recognized as one of the principal pro-inflammatory cytokines in cryopyrin associated periodic syndromes (CAPS).

Omalizumab in the treatment of severe allergic (IgE-mediated) asthma: an update on recent developments

Omalizumab (OMA), a humanized anti-immunoglobulin E (IgE) monoclonal antibody was approved in the EU in 2005 as an add-on therapy for patients with severe persistent allergic asthma (AA). We present an overview of recent developments in the use of OMA for this indication. Approval for pediatric use: followed the completion of two clinical trials in children 6 to <12 years of age with moderate-to-severe AA, who were either well- or inadequately controlled with inhaled corticosteroids (CS). Pooled analysis of these data demonstrated the efficacy and safety of OMA and led to approval in the EU for use in this population.