Arm, Jonathan, Bottoli, Ivan, Skerjanec, Andrej, Groenewegen, Andrea, Maahs, Suzanne, Owen, Charles, Jones, Ieuan and Lowe, Phil (2014) Efficacy and safety of QGE031, a novel anti-IgE antibody, in atopic subjects. Clinical and Experimental Allergy, 44 (11). pp. 1371-1385.

Abstract

Background: Omalizumab has a mid-range affinity for IgE, and the clinical effects of deeper IgE suppression are largely unknown.
Objective: To explore the safety, pharmacokinetics and pharmacodynamics of QGE031, a novel high-affinity anti-IgE antibody.
Methods: Preclinical assessments and two randomized, placebo-controlled, double-blind clinical trials were conducted in atopic subjects. The first trial administered QGE031 (0.1-10 mg/kg) or placebo intravenously, while the second trial administered QGE031 (0.2- 4 mg/kg) or placebo subcutaneously. Both trials included an open-label omalizumab arm.
Results: Sixty of seventy-three (82%) and 96/110 (87%) subjects completed the intravenous and subcutaneous studies, respectively. Exposure to QGE031 and its half-life were dependent on the dose of QGE031 and serum IgE level. QGE031 had a biexponential pharmacokinetic profile after intravenous administration and a terminal half-life of approximately 20 days (subcutaneous study; range, 13-26 days). QGE031 demonstrated dose- and time-dependent suppression of free IgE, basophil FcεRI and basophil surface IgE superior in extent (free IgE and surface IgE) and duration to omalizumab. At Day 85, six weeks after the last dose, skin-prick wheal responses to allergen were suppressed by >95% and 41% in subjects treated subcutaneously with QGE031 (2 mg/kg) or omalizumab, respectively (P < .001). Urticaria was observed in QGE031- and placebo-treated subjects and was accompanied by systemic symptoms in one subject treated with 10 mg/kg intravenous QGE031. There were no serious adverse events.
Conclusion and clinical relevance: These are the first clinical data obtained with QGE031, a novel anti-IgE monoclonal antibody; they demonstrate that increased suppression of free IgE compared with omalizumab translated to superior reduction of pharmacodynamic endpoints in atopic subjects, including those with high levels of IgE. QGE031 may therefore benefit patients unable to receive, or not optimally treated with, omalizumab.

Item Type:	Article
Keywords:	QGE031, IgE, atopic
Date Deposited:	13 Oct 2015 13:13
Last Modified:	13 Oct 2015 13:13
URI:	https://oak.novartis.com/id/eprint/21179