FDA Approves Dupixent® (dupilumab) as First Biologic Medicine for Children Aged 6 to 11 Years with Moderate-to-Severe Atopic Dermatitis
In the pivotal trial, more than twice as many children achieved clear or almost clear skin and more than four times achieved itch reduction with Dupixent plus topical corticosteroids (TCS) compared to TCS alone
Three-quarters of patients receiving Dupixent achieved at least a 75% improvement in overall disease, with an average improvement of approximately 80%
Safety consistent with the established safety profile of Dupixent across adult and adolescent atopic dermatitis patients
"This approval brings the paradigm-changing efficacy and established safety profile of Dupixent to children with moderate-to-severe atopic dermatitis. This young, vulnerable population struggles with debilitating symptoms and disease covering over half of their body, impacting them and their families who spend countless hours helping them manage their disease," said
Dupixent is a fully-human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) proteins, and is not an immunosuppressant. Data from Dupixent clinical trials have shown that IL-4 and IL-13 are key drivers of the type 2 inflammation that plays a major role in atopic dermatitis, asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP). Across all approved indications globally, more than 150,000 patients have been treated with Dupixent.
"This FDA approval is another milestone in the journey for Dupixent as an innovative biologic treatment for atopic dermatitis and other conditions driven in part by type 2 inflammation," said John Reed, M.D., Ph.D., Global Head of Research and Development at Sanofi. "Caregivers of children with moderate-to-severe atopic dermatitis and their physicians now have access to a first-in-class biologic with a proven safety profile, a factor that often plays a critical role in treatment decisions for younger patients. Additionally, improvements in itch and disease severity were observed as early as two weeks after the first dose and continued throughout active treatment, which is important for these children and their families."
The FDA evaluated the Dupixent application under Priority Review, which is reserved for medicines that represent potentially significant improvements in efficacy or safety in treating serious conditions. The FDA previously granted Breakthrough Therapy designation to Dupixent for the treatment of severe atopic dermatitis in children 6 months to 11 years of age not well controlled on topical prescription medications. The Breakthrough Therapy designation was created to expedite the development and review of drugs developed for serious or life-threatening conditions.
Atopic dermatitis, the most common form of eczema, is a chronic inflammatory disease that often appears as a rash on the skin. Moderate-to-severe atopic dermatitis is characterized by rashes that can potentially cover much of the body and can include intense, persistent itching, skin lesions and skin dryness, cracking, redness or darkness, crusting and oozing. Itch is one of the most burdensome symptoms for patients and can be debilitating.
Dupixent comes in two doses, prescribed based on weight (300 mg every four weeks for children ≥15 to <30 kg and 200 mg every two weeks for children ≥30 to <60 kg, following an initial loading dose) as a pre-filled syringe for pediatric patients aged 6 to 11 years.
The FDA approval is based on data that includes pivotal Phase 3 results on the efficacy and safety of Dupixent combined with topical corticosteroids (TCS) compared to TCS alone in children with severe atopic dermatitis. In the trial, children treated with Dupixent and TCS experienced significant improvements in overall disease severity, skin clearance and itch.
Results at 16 weeks showed:
- 84% improvement in average
EASI(Eczema Area and Severity Index) score from baseline in patients who received Dupixent every four weeks and 80% in patients who received Dupixent every two weeks, compared to 49% and 48% for TCS alone, respectively.
- 75% of patients who received Dupixent every four weeks and 75% of patients who received Dupixent every two weeks achieved
EASI-75 (Eczema Area and Severity Index-75), compared to 28% and 26% for TCS alone, respectively.
- 54% of patients who received Dupixent every four weeks and 61% of patients who received Dupixent every two weeks experienced at least a 4-point reduction in itch intensity on a 0 to 10-point scale (weekly average of daily Peak Pruritus Numerical Rating Scale), compared to 12% and 13% for TCS alone, respectively.
- 30% of patients who received Dupixent every four weeks and 39% of patients who received Dupixent every two weeks achieved clear or almost clear skin (Investigator's Global Assessment or IGA), compared to 13% and 10% for TCS alone, respectively.
The safety profile of Dupixent with TCS was similar to what was observed in adults and adolescents with atopic dermatitis, and consistent through 52 weeks. Safety data over the 16-week treatment period showed:
- Overall rates of adverse events (AEs) were 65% for Dupixent every four weeks, 61% for Dupixent every two weeks, and 72% and 75% for TCS alone, respectively.
- AEs that were more commonly observed with Dupixent included upper respiratory tract infections (15% for Dupixent every four weeks, 9% for Dupixent every two weeks, and 8% and 12% for TCS alone, respectively), injection site reactions (10% for Dupixent every four weeks, 14% for Dupixent every two weeks, and 7% and 5% for TCS alone, respectively), nasopharyngitis (10% for Dupixent every four weeks, 3% for Dupixent every two weeks, and 3% and 10% for TCS alone, respectively), conjunctivitis (7% for Dupixent every four weeks, 9% for Dupixent every two weeks, and 3% and 5% for TCS alone, respectively), vomiting (5% for Dupixent every four weeks, 7% for Dupixent every two weeks, and 7% and 7% for TCS alone, respectively) and fever (5% for Dupixent every four weeks, 2% for Dupixent every two weeks, and 7% and 0% for TCS alone, respectively).
Additional prespecified AEs across all weight groups and doses included skin infections (6% for Dupixent every four weeks, 8% for Dupixent every two weeks, and 13% for TCS alone), which is noteworthy because patients with atopic dermatitis have an increased risk of skin infections. In adult atopic dermatitis trials, the incidence of serious skin infections was 57% less with Dupixent compared to the control groups. In addition, in the pediatric trial (6-11 years of age), herpes viral infections occurred in 0% of Dupixent patients every four weeks, 2% of Dupixent patients every two weeks, and 5% for patients on TCS alone.
Dupixent has been studied in more than 8,000 patients ages 6 years and older across more than 40 clinical trials.
Dupixent is an injection under the skin (subcutaneous injection) at different injection sites. In the pediatric (6-11 years of age) population, Dupixent is given either every two weeks (200 mg) or four weeks (300 mg), based on weight, following an initial loading dose. Dupixent is intended for use under the guidance of a healthcare professional and can be given in a clinic or at home by self-administration after training by a healthcare professional. In children younger than 12 years of age, Dupixent should be administered by a caregiver.
Dupixent is also approved in the
Regeneron and Sanofi are committed to helping patients in the
Outside of the
Dupilumab Development Program
In addition to the currently approved indications, Regeneron and Sanofi are also studying dupilumab in a broad range of clinical development programs for diseases driven by allergic and other type 2 inflammation, including pediatric asthma (6 to 11 years of age, Phase 3), pediatric atopic dermatitis (6 months to 5 years of age, Phase 2/3), eosinophilic esophagitis (Phase 3), chronic obstructive pulmonary disease (Phase 3), bullous pemphigoid (Phase 3), prurigo nodularis (Phase 3), chronic spontaneous urticaria (Phase 3), and food and environmental allergies (Phase 2). These potential uses are investigational, and the safety and efficacy have not been evaluated by any regulatory authority. Dupilumab is being jointly developed by Regeneron and Sanofi under a global collaboration agreement.
Dupilumab was invented using Regeneron's proprietary VelocImmune® technology that utilizes a proprietary genetically-engineered mouse platform endowed with a genetically-humanized immune system to produce optimized fully-human antibodies. VelocImmune technology has been used to create multiple antibodies including Libtayo® (cemiplimab-rwlc), Praluent® (alirocumab) and Kevzara® (sarilumab), which are approved in multiple countries around the world. Regeneron previously used these technologies to rapidly develop a treatment for Ebola virus infection, which is currently under review by the FDA, and is now being used in efforts to create prophylactic and treatment medicines for COVID-19.
DUPIXENT is a prescription medicine used:
- to treat people aged 6 years and older with moderate-to-severe atopic dermatitis (eczema) that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies. DUPIXENT can be used with or without topical corticosteroids. It is not known if DUPIXENT is safe and effective in children with atopic dermatitis under 6 years of age.
- with other asthma medicines for the maintenance treatment of moderate-to-severe eosinophilic or oral steroid dependent asthma in people aged 12 years and older whose asthma is not controlled with their current asthma medicines. DUPIXENT helps prevent severe asthma attacks (exacerbations) and can improve your breathing. DUPIXENT may also help reduce the amount of oral corticosteroids you need while preventing severe asthma attacks and improving your breathing. DUPIXENT is not used to treat sudden breathing problems. It is not known if DUPIXENT is safe and effective in children with asthma under 12 years of age.
- with other medicines for the maintenance treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) in adults whose disease is not controlled. It is not known if DUPIXENT is safe and effective in children with chronic rhinosinusitis with nasal polyposis under 18 years of age.
IMPORTANT SAFETY INFORMATION FOR
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:
- have eye problems
- have a parasitic (helminth) infection
- are scheduled to receive any vaccinations. You should not receive a "live vaccine" if you are treated with DUPIXENT.
- are pregnant or plan to become pregnant. It is not known whether DUPIXENT will harm your unborn baby.
- are breastfeeding or plan to breastfeed. It is not known whether DUPIXENT passes into your breast milk.
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; and 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 to come back.
DUPIXENT can cause serious side effects, including:
- Allergic reactions (hypersensitivity), including a severe reaction known as anaphylaxis. Stop using DUPIXENT and tell your healthcare provider or get emergency help right away if you get any of the following symptoms: breathing problems, fever, general ill feeling, swollen lymph nodes, swelling of the face, mouth and tongue, hives, itching, fainting, dizziness, feeling lightheaded (low blood pressure), joint pain, or skin rash.
- Eye problems. Tell your healthcare provider if you have any new or worsening eye problems, including eye pain or changes in vision.
- Inflammation of your blood vessels. Rarely, this can happen in people with asthma who receive DUPIXENT. This may happen in people who also take a steroid medicine by mouth that is being stopped or the dose is being lowered. It is not known whether this is caused by DUPIXENT. Tell your healthcare provider right away if you have: rash, shortness of breath, persistent fever, chest pain, or a feeling of pins and needles or numbness of your arms or legs.
The most common side effects include:
- Atopic dermatitis: injection site reactions, eye and eyelid inflammation, including redness, swelling, and itching, and cold sores in your mouth or on your lips.
- Asthma: injection site reactions, pain in the throat (oropharyngeal pain), and high count of a certain white blood cell (eosinophilia).
- Chronic rhinosinusitis with nasal polyposis: injection site reactions, eye and eyelid inflammation, including redness, swelling, and itching, high count of a certain white blood cell (eosinophilia), trouble sleeping (insomnia), toothache, gastritis, and joint pain (arthralgia).
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. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
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.
Please see full Prescribing Information including Patient Information.
Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune®, which uses unique genetically-humanized mice to produce optimized fully-human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world.
For additional information about the company, please visit www.regeneron.com or follow @Regeneron on Twitter.
Sanofi is dedicated to supporting people through their health challenges. We are a global biopharmaceutical company focused on human health. We prevent illness with vaccines, provide innovative treatments to fight pain and ease suffering. We stand by the few who suffer from rare diseases and the millions with long-term chronic conditions.
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