Regeneron Pharmaceuticals, Inc. and Sanofi today announced positive pivotal Phase 3 results from a trial evaluating Dupixent (dupilumab) to treat moderate-to-severe atopic dermatitis in children aged 6 months to 5 years. The trial met its primary and all secondary endpoints, showing that Dupixent added to standard-of-care topical corticosteroids (TCS) significantly reduced overall disease severity and improved skin clearance, itch and health-related quality of life measures at 16 weeks compared to TCS alone (placebo). Dupixent is the first biologic medicine to show positive results in this young population and remains the only approved biologic medicine in patients 6 years and older with uncontrolled moderate-to-severe atopic dermatitis.
The data reinforce the well-established efficacy and safety profile of Dupixent in other age groups, including a lower observed rate of skin infections in the Dupixent group compared to placebo. During the 16-week treatment period, Dupixent patients were 50% less likely to experience a skin infection (12% Dupixent, 24% placebo), and the total number of infections was nearly 70% lower (11 Dupixent, 34 placebo). These results add to the extensive LIBERTY AD clinical program – the largest Phase 3 clinical trial program in atopic dermatitis involving approximately 3,500 children, adolescents and adults to date.
"Moderate-to-severe atopic dermatitis in infants and young children is incredibly distressing for patients and their caregivers, who manage painful and persistent itch, intensive daily skincare routines such as chlorine baths and wet wraps, as well as sleepless nights for children and their families," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron. "In fact, when starting this trial, the disease covered more than half of children's bodies and nearly a third of patients had previously resorted to using immunosuppressive medicines. These data show that Dupixent dramatically reduced the impact of atopic dermatitis on the lives of these young children and their families, with rapidly cleared skin, improved itch and improved observed patient outcomes, including sleep and skin pain. Importantly, Dupixent provided its benefits without acting as a broad immunosuppressant. In fact, Dupixent-treated patients experienced nearly 70% fewer skin infections compared to placebo patients."
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Atopic dermatitis is a chronic type 2 inflammatory skin disease, with the age of onset younger than 5 years in 85 to 90% of patients. The debilitating symptoms that infants and young children with moderate-to-severe atopic dermatitis experience often continue through adulthood and include intense, persistent itch and skin lesions that can cover much of the body, resulting in skin dryness, cracking, redness or darkening, and crusting and oozing, along with increased risk of skin infections. Moderate-to-severe atopic dermatitis significantly impacts the life of a young child, their parents and caregivers, including their mood, sleep patterns, and quality of life. In addition, the underlying type 2 inflammation involved in atopic dermatitis can contribute to the development of other atopic diseases, like asthma and certain allergies, that may also appear throughout a person's life.
"When a child is diagnosed with moderate-to-severe atopic dermatitis in the first few months of life, many aspects of their childhood can be significantly impacted. Parents and caregivers are challenged to find safe and effective treatment options," said John Reed, M.D., Ph.D., Global Head of Research and Development at Sanofi. "Currently, the standard of care for this patient population is topical steroids and other immunosuppressive medicines may be used which can damage delicate skin and, if used long-term, potentially impact growth. Knowing that safety is of the utmost importance for physicians and parents when considering treatment options for children and infants, we are encouraged by the results of this trial showing Dupixent addressed the signs and symptoms of atopic dermatitis without broadly suppressing the immune system, demonstrating the potential it could have for these very young patients."
Patients received Dupixent every four weeks (200 mg or 300 mg, based on body weight) plus TCS or placebo. The primary endpoints assessed the proportion of patients achieving an Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) and 75% improvement in Eczema Area and Severity Index (EASI-75). The pre-specified primary analysis showed that at 16 weeks, among patients treated with Dupixent:
Dupixent is a fully human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways and is not an immunosuppressant. It was invented using Regeneron's proprietary VelocImmune technology. IL-4 and IL-13 are key and central drivers of the type 2 inflammation that plays a major role in atopic dermatitis, asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP).
Detailed results from this trial will be presented at a future medical meeting, and data will be submitted to regulatory authorities. In 2016, the FDA granted Breakthrough Therapy designation for Dupixent for the treatment of severe atopic dermatitis (in children aged 6 months to 11 years of age). The efficacy and safety of Dupixent in children below the age of 6 years have not been fully evaluated by any regulatory authority.
About the Dupixent Trial
LIBERTY AD PRESCHOOL is a two-part Phase 2/3 trial. The Phase 3 randomized, double-blind, placebo-controlled trial (Part B) evaluated the efficacy and safety of Dupixent added to standard-of-care low-potency TCS compared to low-potency TCS alone (placebo) in 162 children aged 6 months to 5 years with uncontrolled moderate-to-severe atopic dermatitis.
The primary endpoints assessed the proportion of patients achieving an Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) and 75% improvement in Eczema Area and Severity Index (EASI-75) at 16 weeks. EASI measures extent and severity of the disease. Itch was assessed using a 0 to 10 Numerical Rating Scale. Patients treated with Dupixent received either 200 mg (for children weighing ≥5 to <15 kg) or 300 mg (for children weighing ≥15 to <30 kg) every four weeks.
In total, there were 162 patients in the trial, the average age was 3.8 years and 61% were male. Approximately 12% of patients were Latino/Hispanic and 19% were Black/African American. On average, patients entered the trial with atopic dermatitis covering 58% of their body, and 29% had previously used systemic immunosuppressants. Furthermore, 81% of these patients had at least one concurrent type 2 inflammatory and/or allergic condition such as allergic rhinitis and asthma.
Part B of the Phase 3 trial was informed by Part A, which was an open-label, single-ascending-dose, sequential cohort Phase 2 trial designed to assess the pharmacokinetics and safety of Dupixent in children aged 6 months to 5 years with uncontrolled severe atopic dermatitis.
Children who completed Part A or Part B of the trial were eligible to enroll in an open-label extension trial to assess the safety and efficacy of long-term treatment with Dupixent in this age group.
Dupixent is currently approved in the U.S., Europe, Japan and other countries around the world for use in specific patients with moderate-to-severe atopic dermatitis, as well as certain patients with asthma or CRSwNP in different age populations. Dupixent is also approved in one or more of these indications in more than 60 countries around the world and more than 300,000 patients have been treated globally.
Dupilumab Development Program
To date, dupilumab has been studied across 60 clinical trials involving more than 10,000 patients with various chronic diseases driven in part by type 2 inflammation.
Regeneron and Sanofi are studying dupilumab in a broad range of diseases driven by type 2 inflammation or other allergic processes, including pediatric asthma (6 to 11 years of age, Phase 3), chronic obstructive pulmonary disease with evidence of type 2 inflammation (Phase 3), pediatric atopic dermatitis (6 months to 5 years of age, Phase 3), eosinophilic esophagitis (Phase 3), bullous pemphigoid (Phase 3), prurigo nodularis (Phase 3), chronic spontaneous urticaria (Phase 3), chronic inducible urticaria-cold (Phase 3), chronic rhinosinusitis without nasal polyposis (Phase 3), allergic fungal rhinosinusitis (Phase 3), allergic bronchopulmonary aspergillosis (Phase 3) and peanut allergy (Phase 2). These potential uses of dupilumab are currently under clinical investigation, and the safety and efficacy in these conditions have not been fully evaluated by any regulatory authority. Dupilumab is being jointly developed by Regeneron and Sanofi under a global collaboration agreement.
About Regeneron's VelocImmune Technology
Regeneron's VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron's President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create approximately a quarter of all original, FDA-approved or authorized fully human monoclonal antibodies currently available. This includes Dupixent, REGEN-COV (casirivimab and imdevimab), Libtayo (cemiplimab-rwlc), Praluent (alirocumab), Kevzara (sarilumab), Evkeeza (evinacumab-dgnb) and Inmazeb (atoltivimab, maftivimab, and odesivimab-ebgn).
DUPIXENT is a prescription medicine used:
IMPORTANT SAFETY INFORMATION FOR U.S. PATIENTS
Do not use if you are allergic to dupilumab or to any of the ingredients in DUPIXENT.
Before using DUPIXENT, tell your healthcare provider about all your medical conditions, including if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.
Especially tell your healthcare provider if you are taking oral, topical, or inhaled corticosteroid medicines; have asthma and use an asthma medicine; or have atopic dermatitis or CRSwNP, and also have asthma. Do not change or stop your corticosteroid medicine or other asthma medicine without talking to your healthcare provider. This may cause other symptoms that were controlled by the corticosteroid medicine or other asthma medicine to come back.
DUPIXENT can cause serious side effects, including:
The most common side effects by indication are as follows:
Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of DUPIXENT. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA.
Use DUPIXENT exactly as prescribed. Your healthcare provider will tell you how much DUPIXENT to inject and how often to inject it. DUPIXENT is an injection given under the skin (subcutaneous injection). If your healthcare provider decides that you or a caregiver can give DUPIXENT injections, you or your caregiver should receive training on the right way to prepare and inject DUPIXENT. Do not try to inject DUPIXENT until you have been shown the right way by your healthcare provider. In children 12 years of age and older, it is recommended that DUPIXENT be administered by or under supervision of an adult. In children younger than 12 years of age, DUPIXENT should be given by a caregiver.
Date: Aug 30, 2021
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