DENVER – After 12 weeks of treatment, a novel oral prostaglandin D2–receptor antagonist significantly suppressed sputum and submucosal eosinophilia without affecting blood eosinophilia levels in patients with eosinophilic asthma, based on results of a single-center randomized trial.
QAW039 given at 225 mg b.i.d. for 12 weeks improved symptom control and asthma-related quality of life, and had a favorable safety profile, lead study author Dr. Rachid Berair said at an international conference of the American Thoracic Society.
QAW039 is under clinical development by Novartis Pharmaceuticals, the sponsor of the trial.
For the study 61 asthmatics with a sputum eosinophil count of 2% or greater were randomized to either QAW039 (30 patients) or placebo (31 patients) for 12 weeks after a 2-week placebo run-in. The study’s primary endpoint was the reduction of sputum eosinophils, while secondary objectives were improvement of asthma control and safety and tolerability. Other endpoints were improvement on the Asthma-related Quality of Life Questionnaire (AQLQ), FEV1, and histologic features of eosinophilic inflammation and airway remodeling, Dr. Berair of the University of Leicester, England, reported.
Dr. Rachid Berair
Mean patient age was 50 years; 90% of patients had asthma at Global Initiative for Asthma (GINA) level IV or greater, while 10% had asthma at GINA V and required up to 10 mg prednisolone daily.
In the trial, patients in the treatment group experienced a 3.5-fold reduction in sputum eosinophils, compared with those in the placebo group (P = .001); as well as a 2.3-fold reduction in submucosal eosinophils, compared with those in the placebo group (P = .041). The numbers of bronchial epithelial eosinophils did not differ between the two groups and there were no significant reductions in blood eosinophil levels between the groups.
Prebronchodilator FEV1 improved in the treatment group compared with the placebo group, but the differences did not reach statistical significance. However postbronchodilator FEV1 improved significantly in the treatment group, compared with the placebo group (P = .020).
The overall AQLQ scores improved significantly in the treatment group, compared with the placebo group (a mean of .59 points; P = .008), as did the AQLQ subdomains of symptoms, activities, emotions, and environmental exposure.
Adverse events were mild and moderate and balanced between both groups. The most common adverse events were respiratory tract infections and asthma exacerbations.
The clinical benefits of QAW039 on the AQLQ, postbronchodilator FEV1, and ACQ7 were no longer evident at 6 weeks after patients stopped taking the drug. “Given the effect of this drug on eosinophils, we can postulate that it would have an effect on asthma exacerbation rates,” Dr. Berair said. “However, our study was not designed nor was of the required duration to show that effect. We need longer studies to look at the effect of this drug on asthma exacerbations.”
The study was sponsored by Novartis. Dr. Berair reported having no relevant financial conflicts.
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