American Thoracic Society International Conference

American Thoracic Society International Conference

Source:

Bacharier LB, et al. Breaking news: Clinical trial results in pulmonary medicine. Presented at: American Thoracic Society International Conference; May 14-19, 2021 (virtual meeting).

Disclosures: Bacharier reports he received speaker fees from AstraZeneca, GlaxoSmithKline, Regeneron and Sanofi; was on the data safety monitoring board for Cystic Fibrosis Foundation and DBV Technologies; and received research support from NIH, Sanofi and Vectura.
May 21, 2021
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Dupilumab reduces severe asthma exacerbations, improves lung function in children

Source:

Bacharier LB, et al. Breaking news: Clinical trial results in pulmonary medicine. Presented at: American Thoracic Society International Conference; May 14-19, 2021 (virtual meeting).

Disclosures: Bacharier reports he received speaker fees from AstraZeneca, GlaxoSmithKline, Regeneron and Sanofi; was on the data safety monitoring board for Cystic Fibrosis Foundation and DBV Technologies; and received research support from NIH, Sanofi and Vectura.
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Dupilumab significantly reduced asthma exacerbations and improved lung function within 2 weeks in children aged 6 to 11 years with uncontrolled moderate to severe asthma with evidence of type 2 inflammation.

Treatment with dupilumab (Dupixent, Sanofi/Regeneron) also resulted in significant improvement in asthma symptom control and reduced fractional exhaled nitric oxide (FeNO), according to data presented at the American Thoracic Society International Conference.

Asthma Blocks
Source: Adobe Stock.

“Uncontrolled childhood asthma remains a significant challenge and we still have many children who are experiencing compromises in their quality of life and activities due to uncontrolled asthma. Over the last two decades, we've been very fortunate to see the development of biologic therapies for asthma which have served to greatly improve the lives of many asthmatic patients and, over time, we've been able to begin to study those therapies in younger patients,” Leonard B. Bacharier, MD, professor of pediatrics at Monroe Carroll Jr. Children’s Hospital at Vanderbilt University, told Healio. “Now we're having the great opportunity to examine the efficacy of one of these therapies in children as young as 6 years of age to see if the effect of this therapy in younger children and school-aged children is effective, as has been demonstrated in in adolescents and adults.”

The phase 3, randomized, double-blind, placebo-controlled LIBERTY ASTHMA VOYAGE trial evaluated the efficacy and safety of dupilumab, a fully human monoclonal antibody that inhibits signaling of the interleukin-4 and interleukin-13 proteins. The trial enrolled 408 children aged 6 to 11 years with uncontrolled moderate to severe uncontrolled asthma who were treated with a medium-dose inhaled corticosteroid (ICS) with a second controller or a high-dose ICS with or without a second controller. More than 90% of children in the trial had at least one concurrent type 2 inflammatory condition, including atopic dermatitis and eosinophilic esophagitis.

Children were randomly assigned to receive subcutaneous dupilumab 100 mg or 200 mg, based on body weight at study initiation, or placebo every 2 weeks for 52 weeks. The primary analysis evaluated two prespecified populations with evidence of type 2 inflammation: patients with baseline blood eosinophils > 300 cells/µL (n = 259) and patients with the type 2 inflammatory asthma phenotype (FeNO > 20 ppb or blood eosinophils > 150 cells/µL; n = 350).

Healio previously reported topline results of the LIBERTY ASTHMA VOYAGE trial announced in October 2020.

“Dupilumab reduced the annualized rate of severe exacerbations in all efficacy populations,” Bacharier said during the presentation.

The primary endpoint was annualized severe asthma exacerbation rate, which was reduced by 65% (P < .0001) in children with blood eosinophils > 300 cells/µL and 59% (P < .0001) in those with the type 2 inflammatory phenotype at 52 weeks compared with placebo (0.24 events per year and 0.31 events per year, respectively, with dupilumab vs. 0.67 and 0.75, respectively with placebo). The researchers reported similar findings in other populations identified by individual markers of type 2 inflammation (61% reduction in those with blood eosinophils > 150 cells/µL and 62% reduction in those with FeNO > 20 ppb) and in the intention-to-treat population (54% reduction), according to the presentation.

Dupilumab also led to rapid and sustained improvement in lung function, with improvement observed as early as 2 weeks and sustained for up to 52 weeks. At 12 weeks, children assigned dupilumab improved their lung function by 5.32 and 5.21 percentage points compared with placebo (P = .0036 and P = .0009, respectively), according to a company press release. The researchers observed similar results in those with blood eosinophils > 300 cells/µL and those with the type 2 inflammatory phenotype.

In addition, dupilumab also led to improved asthma control. Compared with placebo, children receiving dupilumab showed improved asthma control on the Asthma Control Questionnaire-7 by an additional 0.46 and 0.33 points at 24 weeks (P < .0001).

“Improvements in asthma control scores occurred rapidly after treatment initiation in the dupilumab and placebo groups and the primary efficacy populations. Although clinically meaningful improvements were seen in both treatment groups, there was a marked difference between patients on dupilumab vs. those on placebo by the end of the treatment period,” Bacharier said during the presentation.

Results presented also showed a significant reduction in mean FeNO levels to below the threshold for type 2 inflammation. Children assigned dupilumab had an average improvement in FeNO levels by -20.59 ppb and -17.84 ppb compared with placebo from baseline to 12 weeks (P < .0001 for both), according to the release.

The safety results were generally consistent with the known safety profile of dupilumab in individuals aged 12 years and older with uncontrolled moderate to severe asthma, according to the release. Treatment-emerged adverse events were reported in 83% of children assigned dupilumab vs. 80% assigned placebo. The most common adverse events reported in the dupilumab group were injection-site reaction, viral upper respiratory tract infection and eosinophilia.

“In children as young as 6 years of age, the addition of the biologic dupilumab in children with moderate to severe uncontrolled asthma, and especially amongst those who have a type 2 inflammatory patterns, the addition of dupilumab results in clinically important reductions in their risk of severe exacerbations requiring oral steroids, provides substantial improvement in their FEV1 and improves their asthma control,” Bacharier told Healio. “This should then translate to improved life experiences for these children.”

An open-label extension study of the LIBERTY ASTHMA VOYAGE trial is currently ongoing, with anticipated conclusion later this year, Bacharier told Healio.

An FDA decision for children with moderate to severe asthma is expected by October, according to the release.

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