Results from the phase 3 Liberty Asthma Quest trial demonstrated that the investigational drug, dupilumab, reduced severe exacerbations and improved lung function in patients with uncontrolled persistent asthma, according to a press release issued by Regeneron Pharmaceuticals and Sanofi.
“Approximately one million U.S. adults and adolescents live with uncontrolled, persistent asthma, and continue to experience serious asthma attacks, despite taking an intensive regimen of standard therapies,” George D. Yancopoulos, MD, PhD, president and chief scientific officer of Regeneron, said in the release. “Dupilumab has now demonstrated positive late-stage results in two serious allergic diseases — asthma and atopic dermatitis — with robust efficacy and an extensive safety database. These results continue to support our hypothesis that the [interleukin (IL)]-4/IL-13 pathway is a critical driver of allergic disease, and we remain committed to further investigating the IL-4/IL-13 pathway in other allergic diseases.”
In the trial, researchers enrolled 1,902 patients (1,795 adults; 107 adolescents) with uncontrolled persistent asthma from 413 international study sites. Participants were assigned to receive 200 mg of dupilumab every other week with a loading dose of 400 mg; 300 mg of dupilumab every other week with a loading dose of 600 mg; or one of two separate placebos. Researchers randomly assigned patients 2:1 to active drug or placebo.
During the study, participants continued their standard therapies, including medium- or high-dose inhaled corticosteroid and up to two additional controller medicines. Researchers evaluated two primary endpoints: the annualized rate of severe exacerbation events at 52 weeks and the absolute change from baseline in lung function at 12 weeks, which was measured using pre-bronchodilator forced expiratory volume in 1 second (FEV1).
Results showed that the 300 mg dupilumab dose group demonstrated a 46% reduction in severe asthma attacks in the overall population, a 60% reduction in patients with 150 eosinophilic cells/µL or greater, and a 67% reduction in patients with 300 eosinophilic cells/µL or greater at 52 weeks (P for all < .001).
Compared with placebo, the mean improvement in lung function in the 300 mg dupilumab dose group at 12 weeks was 9% in the overall population, 11% in patients with 150 eosinophilic cells/µL or greater, and 18% in patients with 300 eosinophilic cells/µL or greater (P for all < .001).
The researchers also noted that rates of exacerbations and lung function were comparable between the 200 mg and 300 mg dupilumab dose groups. The dupilumab and placebo groups had similar overall rates of adverse events, deaths, infections, conjunctivitis, herpes and discontinuations, but reactions at the injection site occurred more often in the dupilumab groups than the placebo groups (17% vs. 8%).
“We believe that therapies like dupilumab, which focus on specific molecular pathways such as the [T helper type 2] pathway associated with multiple chronic allergic diseases, are important targets for further investigations,” Elias Zerhouni, MD, president of global R&D at Sanofi, said. "The positive data from this large second pivotal trial in uncontrolled persistent asthma, following the positive results of dupilumab in atopic dermatitis, further support this view in our opinion. We will work diligently with health authorities to bring this new application of dupilumab to the patients who most need it."
Disclosures: Healio Internal Medicine was unable to obtain relevant financial disclosures for the study authors at the time of publication.