Chronic obstructive pulmonary disease patients with type 2 inflammation may soon gain access to a new drug — dupilumab — that showed rapid and sustained improvements in patients in a pivotal Phase 3 clinical trial, researchers report in the New England Journal of Medicine. This monoclonal antibody is the first biologic shown to improve clinical outcomes in COPD. The data supporting the use of dupilumab in COPD will be reviewed by the United States Food and Drug Administration in June.
The disease improvements — as measured by a significantly lower annualized rate of acute exacerbations and significantly better lung function than placebo-treated adults with COPD — were observed at 12 weeks after the initiation of dupilumab and were sustained throughout the 52-week trial period. In terms of safety, the number of adverse events was similar between placebo and treatment groups and consistent with the established profile of dupilumab.
The lung disease COPD is marked by cough and labored breathing. COPD has traditionally been thought of as an inflammatory disease predominantly driven by neutrophilic inflammation. About 20 percent to 40 percent of COPD patients have COPD with a predominant type 2 inflammation that is commonly detected by elevated blood eosinophil counts. These patients have a high risk of exacerbations.
“Dupilumab substantially decreases exacerbation frequency and improves lung function as well as symptom burden in patients with COPD with type 2 inflammation and high exacerbation risk, who are already on maximal inhaled therapy,” said Surya Bhatt, M.D., a professor of medicine and endowed professor of airways disease in the University of Alabama at Birmingham Department of Medicine Division of Pulmonary, Allergy and Critical Care Medicine.
Bhatt and Klaus Rabe, M.D., Ph.D., a professor of pulmonary medicine at the LungenClinic Grosshansdorf, Grosshansdorf, Germany, co-led the international multicenter clinical study that had 470 patients in the dupilumab group and 465 patients in the placebo group. The patients ranged in age from 40 to 85.
The just completed trial replicates an initial, nearly identical, Phase 3 clinical trial of dupilumab reported in NEJM by Bhatt and Rabe last year. The current Phase 3, randomized, double-blind, placebo-controlled trial was needed to confirm findings of that first trial for COPD patients with blood eosinophil counts of 300 cells per microliter or higher and an elevated exacerbation risk, despite being on inhaled triple therapy. Carefully designed clinical trials produce data that allows the FDA to determine whether benefits of an investigational drug outweigh any known and potential risks for its intended population.
COPD patients often have disease exacerbations that can lead to an increased risk of subsequent exacerbations, accelerated lung-function decline and an increased risk of death. Thus, says Bhatt, improving lung function and reducing exacerbations are unmet needs in patients with COPD.
“COPD is the third leading cause of death globally,” Bhatt said. “Exacerbations of COPD lead to poorer quality of life, increased hospitalizations and an increased risk of death.”