A Novel Approach to Managing Patients with Allergic Asthma

On Day 2 of the 2010 World Vaccine Congress in Lyon, France, Martin Bachmann, Chief Scientific Officer of Cytos Biotechnology, discussed a novel approach to managing patients with allergic asthma. He said that allergic asthma, the most common form of asthma, has become dramatically more prevalent in the past century. According to Bachmann, one possible explanation for the increasing frequency of asthma may be “reduced exposure to environmental pathogens in modern societies.” He said that this idea, which may be “summarized under the umbrella of the ‘hygiene hypothesis,’” suggests that “lower rates of infection with bacteria and viruses may skew the immune system towards a so-called ‘T-helper type 2 response,’ leading to allergic diseases including asthma, allergic rhinitis, and atopic dermatitis.”

In order to shift the immune response to a more balanced “type-1 and regulatory T cell response,” Bachmann said that Cytos Biotechnology has developed a natural protein-based nanoparticle filled with a potent stimulator of the innate immune system, a ligand for toll-like receptor 9 (TLR9). This receptor “binds bacterial DNA originating from an infection and prepares the immune system for a counterattack, inducing a normal anti-microbial T-helper type-1 immune response and suppressing type-2 responses that lead to asthma and allergies,” he said. The resulting TLR9 ligand loaded nanoparticle (QbG10) therefore “aims at treating the cause of allergic asthmatic inflammation and should provide patients with a novel therapeutic alternative that could either replace or complement commonly used asthma medications, such as inhaled corticosteroids, while maintaining or improving asthma control.”

Previous studies have shown QbG10 to be safe and efficacious for treatment of allergic rhinitis. Bachmann discussed results from a recent study that aimed to find out whether QbG10 may show a similar efficacy profile for treatment of asthma, a chronic inflammatory disorder of the airways that causes breathlessness, chest tightness, coughing and wheezing.

This randomized, placebo-controlled, multicenter, phase II trial involved 63 patients suffering from persistent allergic asthma that required maintenance therapy with inhaled corticosteroids (ICS) to achieve asthma control. Bachmann said patients were randomized to treatment with either CYT003-QbG10 or placebo as add-on treatment for four weeks. At week 4, patients “entered a corticosteroid reduction phase, where the ICS dose was initially reduced by 50% for the following four weeks and completely withdrawn at week 8 if patients’ clinical stability allowed,” he said.

Under CYT003-QbG10 treatment, daytime and night-time asthma symptoms decreased, while they increased under placebo (p=0.003). At week 12, asthma symptoms had decreased by 33% under QbG10 treatment; they had increased by 29% under placebo (p=0.01). Use of relief medication doubled ( 106%) in the placebo group, but remained stable in the QbG10 group (-4%) (p=0.01). The corresponding combined symptom and medication score improved by 17% in the QbG10 group, but worsened by 71% for the placebo group (p=0.006), with a first significant difference seen already in the second week after the start of treatment.

Lung function (FEV) as assessed by spirometry significantly improved vs. placebo from week 6 onwards. At week 12, FEV1 had decreased on placebo by an average of 251 ml (-8.4%) while it remained stable on QbG10 treatment (-18.5 ml, -0.6%) (p=0.01).

A significant reduction in blood eosinophils under QbG10 therapy versus placebo (p=0.043), and a trend toward reduced exhaled nitric oxide levels in treated patients, showed the anti-inflammatory effects of treatment, which was safe and well tolerated. Bachmann said that local injection site reactions of mostly mild to moderate intensity and two instances of headache were “the only adverse events that were suspected to be associated with treatment and occurred in more than one patient.” He said that these results led researchers to conclude that QbG10 is a highly active drug for the treatment of asthma with great potential for further development.