International study supports dupilumab for treatment of moderate-to-
severe asthma in children

Date:
December 8, 2021
Source:
Vanderbilt University Medical Center
Summary:
In a late-stage clinical trial, the biologic agent dupilumab reduced
the rate of severe asthma attacks and improved lung function and
asthma control for children ages 6 to 11. The findings of the
international multicenter Liberty Asthma VOYAGE trial supported
approval of dupilumab for the treatment of moderate-to-severe asthma
in this age group by the Food and Drug Administration in October.



FULL STORY ==========================================================================
A new medication has been added to the treatment options for children
with moderate-to-severe asthma. In a late-stage clinical trial, the
biologic agent dupilumab reduced the rate of severe asthma attacks and
improved lung function and asthma control for children ages 6 to 11.


==========================================================================
The findings of the international multicenter Liberty Asthma VOYAGE trial, reported Dec. 9 in the New England Journal of Medicine, supported approval
of dupilumab for the treatment of moderate-to-severe asthma in this age
group by the Food and Drug Administration in October.

"This is a really important advance for children with moderate-to-severe
asthma and their families," said Leonard Bacharier, MD, an asthma
specialist at Monroe Carell Jr. Children's Hospital at Vanderbilt and
the international lead investigator for the trial.

Asthma -- a condition that affects the lung's airways and makes it
hard to breathe -- is the most common chronic disorder of childhood,
with more than 5 million children under age 18 affected, according to
the Centers for Disease Control and Prevention. It is a leading cause of hospitalization for children, and children with moderate-to-severe asthma
may have reduced lung function and be at greater risk for lung diseases
in adulthood, said Bacharier, who holds the Janie Robinson and John
Moore Lee Chair in Pediatrics at Vanderbilt University School of Medicine.

"As asthma gets increasingly severe, the burden becomes substantial,
impacting the child and the entire family," he said. "While we have very
good asthma therapies available, none of them are perfect in eliminating
severe exacerbations." Dupilumab, a monoclonal antibody that targets
type 2 inflammation, has been approved for the treatment of asthma in
adults and adolescents for several years. Based on its established
safety and efficacy, the investigators conducted a phase 3 clinical
trial in 408 children between the ages of 6 and 11 who had uncontrolled moderate-to-severe asthma.



========================================================================== Children were randomized to receive a subcutaneous injection of dupilumab
or placebo in addition to their standard therapy every two weeks for
a year.

Neither investigators nor participants knew who received active treatment versus placebo (double-blind trial design).

Most of the children in the trial had markers of type 2 inflammation,
namely elevated levels of immune cells called eosinophils and/or elevated levels of nitric oxide in exhaled air. In patients with these markers, dupilumab significantly reduced the rate of severe exacerbations --
symptoms requiring systemic steroid treatment, need for emergency care
or hospitalization -- by nearly 60%.

In addition, dupilumab improved lung function, measured by forced
exhalation, and improved asthma control, assessed with standardized questionnaires administered by trained interviewers.

"This is the first study of its kind in children ages 6 to 11 that
has demonstrated that a biologic improves asthma exacerbations, lung
function and asthma control," Bacharier said. "We were not surprised,
because dupilumab was very effective in clinical trials in adults and adolescents, but we were delighted with the results and the hope they
bring to children and their families." Dupilumab was not effective for
the small number of children in the trial who did not have evidence of
type 2 inflammation, consistent with expectations, he added.



==========================================================================
The trial demonstrated that dupilumab was safe. Some children receiving
active drug had increases in blood eosinophil levels or mild but
manageable parasitic infections (type 2 immunity fights parasites),
but very few participants had to discontinue dupilumab because of
adverse reactions.

Patients in the VOYAGE trial were invited to join an extension trial for another year, with all participants receiving dupilumab. The extension
trial will focus on both efficacy and long-term safety; results should
be available in mid-2022.

Although two other biologic medicines targeting type 2 inflammation
have been approved to treat asthma in children, neither has demonstrated improvements in all three key clinical endpoints -- asthma exacerbations,
lung function and asthma control -- in a controlled clinical trial,
Bacharier said.

Bacharier plans to explore the potential for dupilumab to modify asthma development. "Can we use this agent earlier in life to change how the
disease develops? I think that's the next frontier," he said.

Bacharier is also a co-investigator of the PrecISE Network (Precision Interventions for Severe Asthma), a National Institutes of Health-funded network that is testing novel asthma therapies in patients with very
severe asthma.

The Liberty Asthma VOYAGE trial (NCT02948959) was supported by Sanofi and Regeneron Pharmaceuticals, the manufacturers of dupilumab. Dupilumab is
also FDA-approved for atopic dermatitis and chronic rhinosinusitis with
nasal polyposis.

========================================================================== Story Source: Materials provided by
Vanderbilt_University_Medical_Center. Original written by Leigh
MacMillan. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Leonard B. Bacharier, Jorge F. Maspero, Constance H. Katelaris,
Alessandro G. Fiocchi, Remi Gagnon, Ines de Mir, Neal Jain,
Lawrence D.

Sher, Xuezhou Mao, Dongfang Liu, Yi Zhang, Asif H. Khan, Upender
Kapoor, Faisal A. Khokhar, Paul J. Rowe, Yamo Deniz, Marcella
Ruddy, Elizabeth Laws, Naimish Patel, David M. Weinreich,
George D. Yancopoulos, Nikhil Amin, Leda P. Mannent, David
J. Lederer, Megan Hardin. Dupilumab in Children with Uncontrolled
Moderate-to-Severe Asthma. New England Journal of Medicine, 2021;
385 (24): 2230 DOI: 10.1056/NEJMoa2106567 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/12/211208182543.htm

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