Sanofi and Regeneron recently announced that the U.
Food and Drug Administration (FDA) has accepted the anti-inflammatory drug Dupixent (Chinese trade name: Dabituo, generic name: dupilumab, dupilumab) ) A supplementary biological product license (sBLA), as an add-on therapy for the treatment of children with moderate to severe asthma who are 6-11 years old and whose condition is uncontrolled.
Currently, Dupixent is approved for patients with moderate to severe asthma who are ≥12 years old, have elevated eosinophils, or rely on oral corticosteroids, and whose condition is uncontrolled.
The FDA has designated the sBLA’s "Prescription Drug User Charges Act" target action date of October 21, 2021.
In the European Union, Dupixent's regulatory application for the treatment of children with asthma from 6 to 11 years old is scheduled to be submitted in the first quarter of 2021.
The sBLA is based on the results of a pivotal phase 3 clinical trial (LIBERTY ASTHMA VOYAGE).
The trial was conducted in children 6-11 years old with uncontrolled moderate to severe asthma.
Data released in October 2020 showed that the trial reached its primary endpoint and all key secondary endpoints.
It is worth mentioning that Dupixent is the first biological agent to improve the lung function of children in a phase 3 controlled trial.
The results showed that in a broad group of patients with type 2 inflammatory asthma (defined as elevated eosinophils [EOS] levels or elevated exhaled nitric oxide [FeNO]), during one year of treatment, with placebo + Compared with standard care, Dupixent+ standard care significantly reduces severe asthma attacks (exacerbations) by 65%, and lung function improves significantly and rapidly within 2 weeks of treatment and lasts for 52 weeks.
In the United States, approximately 75,000 children aged 6-11 suffer from uncontrolled moderate-to-severe asthma, which may bring a heavy burden to children and their families.
Despite the current use of standard care therapies, such as inhaled corticosteroids (ICS) and bronchodilators, these children still experience symptoms such as coughing, wheezing, and difficulty breathing, and may be at risk of life-threatening severe asthma attacks.
These attacks It often leads to frequent hospitalizations and emergency room visits, and may require the use of systemic corticosteroids, which poses significant risks in long-term use.
Uncontrolled moderate to severe asthma can impair lung function and interfere with daily activities such as sleep, school, and exercise.
The results of the LIBERTY ASTHMA VOYAGE study show that Dupixent has the potential to become a best-in-class treatment option for children with asthma from 6 to 11 years old.
LIBERTY ASTHMA VOYAGE is a randomized, double-blind, placebo-controlled trial that enrolled 408 uncontrolled children with moderate to severe asthma (6 years to under 12 years old), and evaluated the addition of Dupixent to labeled care maintenance Efficacy and safety of therapy (medium-dose inhaled corticosteroids [ICS] combined with the second control drug, or: high-dose ICS combined with or without the second drug).
The main analysis was based on 259 patients at baseline (EOS≥300 cells/μl) and 350 patients with type 2 inflammatory markers (baseline EOS≥150 cells/μl or FeNO≥20 ppb).
There is no minimum biomarker requirement at the time of enrollment.
During the 52-week treatment period, patients received a subcutaneous injection of Dupixent 100 mg or 200 mg every 2 weeks (body weight ≤ 30 kg: 100 mg, body weight> 30 kg: 200 mg) according to their body weight, or a subcutaneous injection of placebo every 2 weeks.
The primary endpoint assesses the annualized rate of severe asthma attacks in two main pre-specified populations: patients with EOS ≥ 300 cells/μl in blood at baseline and patients with type 2 inflammatory markers (FeNO ≥ 20 ppb or EOS ≥ 150 cells) /Μl).
In these two patient groups, patients who added Dupixent to the standard of care (100 mg or 200 mg every 2 weeks, based on body weight) experienced:
-Reduced rate of severe asthma attacks: Compared with placebo, an average reduction of 65% (p<0.
0001) and 59% (p<0.
0001) within one year (0.
24 and 0.
31 events per year in the Dupixent group, 0.
67 and 0.
75 events per year in the Dupixent group, respectively) );
——Improvement of lung function: According to the predicted forced expiratory volume per second (FEV1) percentage (FEV1pp), at week 12, Dupixent treatment improved lung function by 10.
15 and 10.
53 percentage points from baseline, compared with 4.
83 and 10.
53 percentage points for placebo patients, respectively 5.
32 percentage points (the least squares average difference between Dupixent and placebo was 5.
3 and 5.
2 percentage points, respectively, p=0.
0036 and p=0.
FEV1pp is a common endpoint in pediatric asthma trials.
It evaluates patients' lung function and predicts changes in lung function based on multiple factors such as age, height, and gender, so as to illustrate the increase in children's vital capacity at different developmental stages.
This clinically significant improvement in lung function was observed as early as 2 weeks and lasted up to 52 weeks.
-The safety results of Dupixent in the trial are consistent with the known safety in patients with moderate to severe asthma 12 years of age and older.
During 52 weeks of treatment, the adverse event rates of Dupixent and placebo were 83% and 80%, respectively.
Compared with the placebo group, the most common adverse reactions in the Dupixent group included injection site reactions (18% for Dupixent and 13% for the placebo group) and viral upper respiratory tract infections (12% for the Dupixent group and 13% for the placebo group) ).
Dupixent targets the key drivers of type 2 inflammation.
The drug is a fully humanized monoclonal antibody that specifically inhibits the over-activation signal of two key proteins, IL-4 and IL-13.
IL-4/IL-13 are two kinds of inflammatory factors, which are considered to be the key driving factors of intrinsic inflammation in allergic diseases and other type 2 inflammatory diseases, including atopic dermatitis, asthma, eosinophilic esophagitis, and herb allergy , Peanut allergy, etc.
Dupixent was launched at the end of March 2017 and has been approved to treat 3 types of diseases caused by type 2 inflammation: moderate to severe atopic dermatitis (patients ≥ 6 years old), moderate to severe asthma (patients ≥ 12 years old), 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.
Darbitux is the world's first and only targeted biological agent approved for the treatment of moderate to severe atopic dermatitis in adults.
It fills the unmet clinical needs in China and can quickly, significantly and continuously improve the skin of patients with atopic dermatitis.
The degree of damage and symptoms of itching.
Thanks to the promotion of the drug regulatory reform, Dabituo was approved in China two years in advance, providing Chinese patients with new treatment options.
At present, Sanofi and Regeneron are also carrying out an extensive clinical project to evaluate Dupixent in the treatment of diseases caused by allergies and other type 2 inflammations, including: childhood asthma (6-11 years old, stage III), childhood atopy Dermatitis (6 months to 5 years, stage II/III), eosinophilic esophagitis (stage III), chronic obstructive pulmonary disease (stage III), bullous pemphigoid (stage III), prurigo nodularis ( Stage III), chronic spontaneous urticaria (stage III), food and environmental allergies (stage II).
Dupixent is another important product jointly developed by Sanofi and Regeneron following the PCSK9 inhibitor lipid-lowering drug Praluent.
It is expected to become a game-changing drug.
At present, Dupixent indications are steadily increasing.
EvaluatePharma, a well-known pharmaceutical market research organization, previously predicted that the drug's global sales in 2024 may reach 8 billion US dollars.
Original source: FDA ACCEPTS DUPIXENT? (DUPILUMAB) FOR REVIEW IN CHILDREN WITH MODERATE-TO-SEVERE ASTHMA