The US Food and Drug Administration (FDA) has approved dupilumab (Dupixent, Sanofi/Regeneron) as "add-on maintenance therapy in patients with moderate-to-severe asthma aged 12 years and older with an eosinophilic phenotype or with oral corticosteroid-dependent asthma," according to a company news release.
The FDA approved dupilumab for moderate-to-severe atopic dermatitis on March 28, 2017.
"Today's approval marks a significant development for certain people with moderate-to-severe asthma aged 12 years and older. For patients dependent on oral corticosteroids, Dupixent improved lung function, reduced oral corticosteroid use, and reduced exacerbations regardless of baseline eosinophil levels," Olivier Brandicourt, MD, chief executive officer, Sanofi, said in the news release.
"Despite the spectrum of treatments for asthma, there continues to be an unmet need for so many patients with moderate-to-severe asthma, and given that Dupixent works differently than other biologics, there is now a new treatment option for some of these patients. Dupixent has already made a difference for many adults with atopic dermatitis, and we now have the opportunity to do the same for certain adults and adolescents with moderate-to-severe asthma in the United States," Brandicourt added.
Dupilumab is an interleukin-4 (IL-4) and interleukin-13 (IL-13) inhibitor; both IL-4 and IL-13 are proteins that stimulate the Type 2 inflammation that forms the basis of moderate-to-severe asthma. Dupilumab reduces inflammatory biomarkers including fractional exhaled nitric oxide, immunoglobulin E, and eotaxin-3.
For the indication of asthma, dupilumab will be available as an injectable solution in prefilled syringes with 200-mg and 300-mg doses administered every other week using different injection sites after a first loading dose. Patients can receive it in a clinic or self-administer it at home after training by a healthcare professional. According to the company news release, dupilumab is the only asthma biologic that can be administered by the patient at home, the only biologic approved by the FDA for patients with moderate and severe asthma with eosinophilic phenotype, and the only biologic approved for patients with oral corticosteroid-dependent asthma, regardless of asthma phenotype.
"Despite being compliant with their current medicine, many people with moderate-to-severe asthma, including those with eosinophilic phenotype or with oral steroid dependence, live with persistent symptoms like unpredictable attacks and difficulty breathing," said Kenneth Mendez, president and chief executive officer of the Asthma and Allergy Foundation of America (AAFA) in the release. "AAFA supports the availability of innovative new treatment options for people with asthma who struggle with uncontrolled symptoms that impair their quality of life."
Three Clinical Trials
The FDA based its decision on results from three randomized, placebo-controlled, multicenter trials that included a total of 2888 adults and adolescents with moderate-to-severe asthma and lasted 24 to 52 weeks. Patients had varying baseline eosinophil levels.
Trial 2 was the largest trial, with 1902 patients; overall, patients experienced fewer exacerbations and had improved lung function. Patients with eosinophil counts ≥ 150 cells/µL (70% of the study population) experienced reductions in exacerbations, and these were most pronounced in those with higher eosinophil counts. In patients with blood eosinophils ≥ 300 cells/µL, severe exacerbations were reduced by 67% in those who took dupilumab compared with placebo, and FEV1 (lung function) improved by 29% to 33%, compared with 14% to 16% for those who received placebo. Severe exacerbation rates did not differ between the dupilumab and placebo groups among the patients with eosinophil counts < 150 cells/µL. The researchers published their findings on June 28, 2018 in the New England Journal of Medicine.
Trial 3 included 210 patients with severe, oral corticosteroid-dependent asthma. Patients who received dupilumab were able to decrease their average daily oral corticosteroid use by 70% compared with 42% for those in the placebo group. More than half of those who received dupilumab completely discontinued oral corticosteroids. Baseline blood eosinophil levels did not appear to affect lung function, oral steroid use, or exacerbation reduction in patients who took dupilumab. Results of this study were also published on June 28, 2018 in the New England Journal of Medicine.
Trial 1 was a phase 2B clinical trial in 776 patients with uncontrolled persistent asthma who were receiving medium-to-high-dose inhaled corticosteroids plus a long-acting β2-agonist. Patients who received dupilumab experienced increased lung function and fewer severe exacerbations irrespective of their eosinophil count at baseline. Dupilumab had a favorable safety profile. The findings were published online April 26, 2016 and in the July issue of The Lancet the same year.
The most common adverse events that occurred in at least 1% of patients who received dupilumab were injection site reactions, sore throat, and increased eosinophil levels.
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Cite this: FDA Approves Dupilumab for Moderate-to-Severe Asthma - Medscape - Oct 22, 2018.
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