FDA Expands Approval of Dupixent® (dupilumab) for Moderate-to-Severe Asthma in Children Aged 6–11

October 21, 2021 -- /BioonBIOON/ -- Sanofi and its partner Regeneron recently jointly announced that the U.S. Food and Drug Administration (FDA) Approved anti-inflammatory drugsDupixent (Chinese trade name: Dabiptuo, generic name: dupilumab) Expanded Patient Population: As an add-on maintenance treatment for pediatric patients aged 6 to 11 years with moderate-to-severe asthma characterized by an eosinophilic phenotype or oral corticosteroid dependence. In the United States, Dupixent was previously approved for the treatment of moderate-to-severeAsthmaPatient.

It is worth noting that,Dupixent is the only biologic approved for the treatment of oral corticosteroid-dependent asthma in children.. In addition,Dupixent is the only one to improve [clinical outcomes] in children aged 6–11 years in a randomized Phase 3 trialAsthmaThe biologic's impact on lung function in pediatric patients supports its potential as a best-in-class option.

Asthma is the most common chronic disease in children. In the United States, approximately 75,000 children aged 6 to 11 years have uncontrolled moderate-to-severe asthma, with many more affected worldwide. Despite receiving current standard-of-care treatment with inhaled corticosteroids and bronchodilators, these children may continue to experience severe symptoms such as cough, wheezing, and shortness of breath. They may also require multiple courses of systemic corticosteroids, which carry significant risks.In children, type 2 inflammation is the most common cause of asthma. Children with asthma and underlying type 2 inflammation are more likely to have poorly controlled asthma and more frequentAsthmaEpisodes and symptoms that interfere with daily activities.

This approval is based on the pivotal Phase 3Clinical TrialResults from (LIBERTY ASTHMA VOYAGE). The trial was conducted in pediatric patients aged 6 to 11 years with uncontrolled moderate-to-severe asthma. Data demonstrate that the trial met the primary endpoint and all key secondary endpoints:In a broad pediatric patient population with type 2 inflammatory asthma (defined as elevated eosinophil [EOS] levels or elevated fractional exhaled nitric oxide [FeNO]), over one year of treatment, Dupixent plus standard of care significantly reduced severe asthma exacerbations by 65% compared with placebo plus standard of care. Lung function improved significantly and rapidly within 2 weeks of treatment and was sustained through Week 52. Additionally, Dupixent significantly improved overall asthma symptom control and reduced fractional exhaled nitric oxide (FeNO), which wasAsthmaairways in which type 2 inflammation plays a predominant roleBiomarker。

ChildrenAsthmaSeizure (Image credit: activemomsnetwork.com)

LIBERTY ASTHMA VOYAGE was a randomized, double-blind, placebo-controlled Phase 3 trial that enrolled 408 patients with uncontrolled moderate-to-severeAsthmaIn pediatric patients (aged 6 to <12 years), the efficacy and safety of Dupixent (100 mg or 200 mg subcutaneously every 2 weeks, based on body weight) in combination with standard-of-care maintenance therapy (medium-dose inhaled corticosteroids [ICS] plus a second controller medication, or high-dose ICS with or without a second controller medication) were evaluated. In this trial, more than 90% of pediatric patients had at least one concurrent type 2 inflammatory disease.

Results showed that patients with a baseline blood eosinophil (EOS) count ≥300 cells/μL (n=259) who received add-on treatment with Dupixent (100 mg or 200 mg every 2 weeks, based on body weight) to standard of care experienced:

—— SevereAsthmaExacerbation rate reduced, with an average reduction of 65% over one year compared with placebo (p<0.0001) (0.24 events/year in the Dupixent group vs. 0.67 events/year in the placebo group);

——Improvement in lung function: observed as early as Week 2 of treatment and sustained through Week 52. Based on percent predicted forced expiratory volume in 1 second (FEV1pp), at Week 12, treatment with Dupixent improved lung function by 5.32 percentage points compared with placebo (p=0.0036). FEV1pp is pediatricAsthmaA common clinical trial endpoint that assesses the change in a patient's lung function relative to predicted values based on factors such as age, height, and sex, to demonstrate the increase in vital capacity across different developmental stages in children.

——Significant improvement in asthma control at Week 24: this was based on patient-reported disease symptoms and impact, usingAsthmaMeasured as a ≥0.5-point improvement in the Asthma Control Questionnaire (ACQ-7-IA, 7-point scale) score, 81% of patients in the Dupixent treatment group reported a clinically meaningful improvement, compared with 64% in the placebo group.

——Mean fractional exhaled nitric oxide (FeNO) levels were significantly reduced, falling below the threshold for type 2 inflammation (≥20 ppb): children with elevated FeNO levels were also evaluated, and in this subgroup, those receiving Dupixent added to standard of care experienced severeAsthmaReduction in attack frequency.

The safety results of this trial are consistent with the known safety profile in patients aged 12 years and older with moderate to severeAsthmaThe safety profile of Dupixent was generally consistent across patients. The overall incidence of adverse events for Dupixent and placebo was 83% and 80%, respectively. The most commonAdverse ReactionsIncluding injection site reactions (Dupixent 18%, placebo 13%), viral upper respiratory tract infections (Dupixent 12%, placebo 10%), and eosinophilia (Dupixent 6%, placebo 1%).

Dupixent targets the key drivers of type 2 inflammation. It is a fully human monoclonal antibody that specifically inhibits the overactivated signaling of two key proteins, IL-4 and IL-13. IL-4/IL-13 are two inflammatory cytokines believed to be key drivers of the underlying inflammation in allergic diseases and other type 2 inflammatory conditions, including atopic dermatitis,Asthma, eosinophilic esophagitis, grass allergy, peanut allergy, etc.

Dupixent was launched in late March 2017 and is currently approved for the treatment of three diseases driven by type 2 inflammation: moderate-to-severe atopic dermatitis (in patients aged ≥6 years), moderate-to-severeAsthma(patients aged ≥6 years), chronic rhinosinusitis with nasal polyps (CRSwNP, adult patients).

In China, in June 2020, Dupixent was approved by the National Medical Products Administration (NMPA) for the treatment of moderate-to-severe atopic dermatitis (AD) in adults.Dupixent is the world's first and only approved targeted biologic for the treatment of moderate-to-severe atopic dermatitis in adults, addressing an unmet clinical need in China by rapidly, significantly, and sustainably improving the severity of skin lesions and pruritus in patients with atopic dermatitis. Driven by regulatory reforms, Dupixent was approved in China two years ahead of schedule, providing Chinese patients with a novel treatment option.

Currently, Sanofi and Regeneron are also conducting an extensive clinical program evaluating Dupixent for diseases caused by allergies and other type 2 inflammation, including: chronic obstructive pulmonary disease (Phase 3), atopic dermatitis in children aged 6 months to 5 years (Phase 3), eosinophilic esophagitis (Phase 3), bullous pemphigoid (Phase 3), prurigo nodularis (Phase 3), chronic spontaneous urticaria (Phase 3), chronic inducible urticaria (Phase 3), chronic rhinosinusitis without nasal polyps (Phase 3), allergic fungal rhinosinusitis (Phase 3), allergic bronchopulmonary aspergillosis (Phase 3), and peanut allergy (Phase 2). (Bioon.com)

Source:FDA Expands Approval of Dupixent® (dupilumab) to Include Children Aged 6 to 11 Years with Moderate-to-severe Asthma