The novel TLR-9 agonist QbG10 shows clinical efficacy in persistent allergic asthma

Background: Allergen-specific T(H)2 responses contribute to the development of allergic asthma. Their increase may be due to a reduced early exposure to environmental pathogens, which induces a T(H)1 response, and thereby suppresses the allergic T(H)2 response. QbG10 (bacteriophage Qbeta-derived virus-like particle with CpG-motif G10 inside), a novel Toll-like receptor 9 agonist packaged into virus-like particles, was designed to stimulate the immune system toward a T(H)1-mediated protective response. Objective: We examined clinical efficacy, safety, and tolerability of QbG10 with patient-reported and objective clinical outcome parameters in patients with mild-to-moderate persistent allergic asthma. Methods: In this proof-of-concept parallel-group, double-blind, randomized trial, 63 asthmatic patients followed conversion to a standardized inhaled steroid and were treated with 7 injections of either QbG10 or placebo. Incorporating a controlled steroid withdrawal, the effects on patient-reported (day- and nighttime asthma symptoms, salbutamol usage, and 7-item-Asthma Control Questionnaire scores) and objective clinical outcome measures (FEV1, fraction of exhaled nitric oxide, and blood eosinophils) were assessed over 12 weeks (ClinicalTrials.gov number, NCT00890734). Results: All patient-reported parameters improved overall between week 0 and 12 in QbG10-treated patients (n=33) despite steroid withdrawal, compared with deteriorations observed under placebo (n=30, P<.05). At week 12, two thirds of the QbG10-treated patients had their asthma "well controlled'' (Asthma Control Questionnaire score <= 0.75) compared with one third under placebo. FEV1 had worsened to a clinically significant extent in patients on placebo, while it remained stable in QbG10 patients. Adverse events were mostly injection site reactions occurring after QbG10 administration. Conclusion: Treatment with QbG10 may contribute to continued asthma control during steroid reduction in patients on moderate or high-dose inhaled steroids. (J Allergy Clin Immunol 2013;131:866-74.)