Dupilumab reduces exacerbations in patients with uncontrolled asthma

DENVER — The addition of dupilumab to treatment with inhaled corticosteroids and long-acting beta agonists improved lung function and reduced the annualized severe exacerbation rate in patients with moderate to severe asthma, according to results of a phase 2b study presented at the American Thoracic Society International Conference.

“Dupilumab added to combination therapy demonstrated an improvement in [forced expiratory volume in 1 second (FEV₁)], both in liters and percent, from baseline to 12 weeks, a reduction in severe asthma exacerbations and a decrease in exhaled nitric oxide levels from baseline to 12 weeks,” Sally E. Wenzel, MD, of the division of pulmonary, allergy and critical care medicine at University of Pittsburgh, said during a presentation.

Wenzel and colleagues conducted a 24-week multinational, randomized, placebo-controlled study that included 769 patients aged 18 years and older with uncontrolled physician-diagnosed asthma. Patients received different doses and regimens of dupilumab (Regeneron Pharmaceuticals and Sanofi), a fully human monoclonal antibody. Researchers evaluated efficacy and safety at 12 weeks.

Researchers assigned participants to placebo (n = 158), 200 mg dupilumab every 4 weeks (n = 150), 300 mg dupilumab every 4 weeks (n = 157), 200 mg dupilumab bi-weekly (n = 148), or 300 mg dupilumab bi-weekly (n = 156).

Researchers assessed results based on participants’ baseline eosinophil count (< 300/µL or ≥ 300/µL).

Compared with placebo, dupilumab improved FEV₁ at week 12 in patients with high eosinophils at all doses except 200 mg every 4 weeks (P < 0.03).

All but one dupilumab regimen — 300 mg every 4 weeks — reduced severe asthma exacerbation rates better than placebo in the high eosinophil population and the overall population (P < .001).

Researchers reported comparable incidence of adverse events among patients assigned dupilumab (69.9% to 73.9%) and those assigned placebo (66.5%). Injection site reaction was the most common adverse event, occurring in 12.7% to 25% of patients assigned dupilumab and 12% of patients assigned placebo.

The findings suggest further research into dupilumab in this patient population is warranted, researchers concluded.

“A phase 3 trial is currently recruiting and will include patients with all baseline eosinophil levels,” Wenzel said. – by Ryan McDonald

Reference:

Wenzel SE, et al. A6362. Presented at: American Thoracic Society International Conference; May 15-20, 2015; Denver.

Disclosure: Wenzel reports receiving travel expenses from Sanofi.