Dupixent (Dupilumab) Significantly Reduces Asthma Exacerbations and Improves Lung Function in Children Aged 6–11 with Uncontrolled Moderate-to-Severe Asthma: Pivotal Phase 3 Data

May 19, 2021 /BioonBIOON/ -- Sanofi recently announced a pivotal Phase 3 trial evaluating the anti-inflammatory drug Dupixent (Chinese brand name: Dabito, generic name: dupilumab) for the treatment of pediatric patients (aged 6-11 years) with uncontrolled moderate-to-severe asthma with evidence of type 2 inflammation.Clinical Trialdetailed results of (LIBERTY ASTHMA VOYAGE). The data show that,Dupixent significantly reduced severe asthma exacerbations and rapidly improved lung function within 2 weeks.. Additionally, Dupixent also significantly improved overall asthma symptom control and reduced exhaled nitric oxide (FeNO), which isAsthmaairways in which type 2 inflammation plays a major roleBiomarker. These data were presented at the recently held 2021 American Thoracic Society InternationalConferencepublished at (ATS 2021).

It is worth noting that, Dupixent is the only biologic to improve lung function in a randomized phase 3 trial in children aged 6 to 11 years with uncontrolled moderate-to-severe asthma, and has the potential to become a best-in-class therapy for this patient population.Key data presented at the ATS 21 conference showed that Dupixent can significantly reduce pediatric...Asthmaexacerbations, improved lung function, and the results further support the favorable safety profile of Dupixent.

Currently, a supplemental Biologics License Application (sBLA) for Dupixent is under review by the USFDAReview: As an add-on therapy for the treatment of pediatric patients aged 6 to 11 years with uncontrolled moderate-to-severe asthma. In the United States, Dupixent has been approved for patients aged ≥12 years with uncontrolled moderate-to-severe asthma characterized by elevated eosinophils or oral corticosteroid dependence.AsthmaPatient.FDAThe review decision will be made by October 21, 2021.

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 even more children affected worldwide. Despite treatment with the current standard-of-care regimen of 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 underlying cause of asthma. Children with asthma and underlying type 2 inflammation are more likely to experience poorly controlled asthma and more frequentAsthmaEpisodes and symptoms that interfere with daily activities.

Leonard B. Bacharier, Principal Investigator of the study, Director of the Center for Childhood Asthma Research at Monroe Carell Jr. Children's Hospital at Vanderbilt University Medical Center, and Professor of Pediatrics, stated: “The trial results show that when added to the standard of care, Dupixent significantly reduces asthma exacerbations, rapidly improves lung function, and improves# AsthmaControl, which is especially important for these children during a critical developmental period in their lives.”

LIBERTY ASTHMA VOYAGE is a randomized, double-blind, placebo-controlled trial that enrolled 408 patients with moderate-to-severe uncontrolledAsthmaIn pediatric patients (aged 6 to <12 years), the efficacy and safety of adding Dupixent (100 mg or 200 mg subcutaneously every 2 weeks, based on body weight) to 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. Two pre-specified populations with evidence of type 2 inflammation were used for the primary analysis: (1) patients with baseline blood eosinophils (EOS) ≥300 cells/μL (n=259); (2) patients with baseline FeNO ≥20 ppb or EOS ≥150 cells/μL (n=350).

The results for the primary and key secondary endpoints of this trial were both reported in October 2020. These data demonstrated that, in both patient groups, patients who received Dupixent added to standard of care experienced:

——SevereAsthmaReduction in attack frequency: compared with placebo, a mean reduction of 65% (p<0.0001) and 59% (p<0.0001) over one year (0.24 and 0.31 events per year in the Dupixent group vs. 0.67 and 0.75 events per year, respectively, in the placebo group);

——Improvement in Pulmonary Function: First observed as early as Week 2 of treatment and sustained through Week 52. Based on the percent predicted forced expiratory volume in 1 second (FEV1pp), at Week 12, treatment with Dupixent improved lung function by 5.32 and 5.21 percentage points compared with placebo (p=0.0036 and p=0.0009). FEV1pp is the pediatricAsthmaA common endpoint in clinical trials that evaluates the difference between a patient's observed pulmonary function and predicted pulmonary function based on multiple factors such as age, height, and sex, to demonstrate the increase in vital capacity across different developmental stages in children.

Pediatric asthma attack (Image source: activemomsnetwork.com)

New data presented at the ATS conference——Results presented for the first time at the ATS meeting across two major patient populations showed that patients treated with Dupixent experienced:

——Significant improvement in asthma control at week 24: This is based on patient-reported disease symptoms and impact, measured on a 0–6 scale. On average, patients treated with Dupixent showed score improvements of 1.34 and 1.33 points from baseline, compared with 0.88 and 1.00 points in the placebo group (mean score improvement for Dupixent vs. placebo = −0.46 and −0.33; p<0.0001 and p=0.0001, respectively). InAsthmaIn terms of the ACQ-7-IA, the improvement from baseline in patients treated with Dupixent was more than twice the clinically meaningful threshold of 0.5 points.

——Mean FeNO levels significantly decreased, below the threshold for type 2 inflammation (20 ppb). From baseline to Week 12, compared with the placebo group, patients treated with Dupixent showed mean improvements in FeNO levels of -20.59 and -17.84 ppb (both p < 0.0001).

The safety results of this trial were 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 was 83% for Dupixent and 80% for placebo. 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 considered to be key drivers of underlying inflammation in allergic diseases and other type 2 inflammatory diseases, including atopic dermatitis,Asthma、Eosinophilic esophagitis, grass allergy, peanut allergy, etc.

Dupixent was launched in late March 2017 and is currently approved to treat three diseases caused by type 2 inflammation: moderate-to-severe atopic dermatitis (in patients aged ≥6 years), moderate-to-severeAsthma(patients aged ≥12 years), chronic rhinosinusitis with nasal polyps (CRSwNP, adult patients).

In China, in June 2020, Dupixent (Dabitu) 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. It delivers rapid, significant, and sustained improvement in the extent of skin lesions and pruritus for patients with atopic dermatitis. Driven by drug regulatory reforms, Dupixent was approved in China two years ahead of schedule, providing a novel treatment option for Chinese patients.

Currently, Sanofi and Regeneron are also conducting an extensive clinical program evaluating Dupixent for the treatment of diseases driven by allergies and other type 2 inflammation, including: children`Asthma`(Aged 6–11 years, Phase III), pediatric atopic dermatitis (6 months to 5 years, Phase II/III), eosinophilic esophagitis (Phase III), chronic obstructive pulmonary disease (Phase III), bullous pemphigoid (Phase III), prurigo nodularis (Phase III), chronic spontaneous urticaria (Phase III), food and environmental allergies (Phase II). (Bioon.com)

Original Source: Pivotal data at ATS 2021 show Dupixent (dupilumab) significantly reduced asthma attacks and improved lung function in children