- U.S. FDA submission for children planned for 4Q 2019
PARIS and TARRYTOWN, NY--(BUSINESS WIRE)--A pivotal Phase 3 trial evaluating Dupixent® (dupilumab) to treat severe atopic dermatitis in children aged 6 to 11 years met its primary and secondary endpoints. Dupixent is the first and only biologic to show positive results in this pediatric atopic dermatitis population.
The topline data show that for children with severe atopic dermatitis (covering nearly 60% of their skin surface on average), adding Dupixent to standard-of-care topical corticosteroids (TCS) significantly improved measures of overall disease severity, skin clearing, itching and health-related quality of life, compared to TCS alone. In addition, the safety data were consistent with the previously documented safety profile of Dupixent in older populations, including a numerically lower rate of skin infections compared to placebo.
“The results from this trial, the first to assess a biologic medicine in children under 12 with atopic dermatitis, are very important because of the significant unmet needs in this patient population. Children in the trial had suffered from severe atopic dermatitis for most of their lives,” said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer of Regeneron. “The trial showed that Dupixent significantly improved outcomes and quality of life, with no new safety signals.
Dupixent is a fully-human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) proteins. 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).
“In this trial, children with severe atopic dermatitis had uncontrolled disease covering, on average, nearly 60% of their skin. The unrelenting symptoms of this disease, which impact not just the child but the whole family, include widespread rashes, intense and persistent itching, and skin lesions,” said John Reed, M.D., Ph.D., Global Head of Research and Development at Sanofi. "Symptoms of severe atopic dermatitis can take a toll on children both physically and emotionally. We are encouraged by these results, which demonstrate that Dupixent improved skin lesions, reduced itching, cleared the skin and importantly, improved health-related quality of life measures for these young patients.”
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 co-primary endpoint outside of the U.S.) at 16 weeks.
Results at 16 weeks included:
- 33% of patients who received Dupixent every four weeks (300 mg) and 30% of patients who received Dupixent every two weeks (100 mg or 200 mg, based on weight) achieved clear or almost clear skin (IGA; score of 0 or 1), compared to 11% for placebo (p<0.0001 and p=0.0004, respectively).
- 70% of patients who received Dupixent every four weeks and 67% of patients who received Dupixent every two weeks achieved 75% or greater skin improvement (EASI-75), compared to 27% for placebo (p<0.0001 for both).
- The average EASI score improvement from baseline was 82% in the Dupixent every four weeks group and 78% in the Dupixent every two weeks group, compared to 49% for placebo (p<0.0001 for both).
- Dupixent demonstrated significant itch relief, and also improved measures of patient-reported outcomes, such as anxiety, depression and health-related quality of life of parents and family members.
For the 16-week treatment period, the overall rates of adverse events were 65% for Dupixent every four weeks, 67% for Dupixent every two weeks and 73% for placebo. Adverse events that were more commonly observed with Dupixent included conjunctivitis (7% for Dupixent every four weeks, 15% for Dupixent every two weeks and 4% for placebo), nasopharyngitis (13% for Dupixent every four weeks, 7% for Dupixent every two weeks and 7% placebo) and injection site reactions (10% for Dupixent every four weeks, 11% for Dupixent every two weeks and 6% for placebo). Additional prespecified adverse events included skin infections (6% for Dupixent every four weeks, 8% for Dupixent every two weeks and 13% for placebo) and herpes viral infections (2% for Dupixent every four weeks, 3% for Dupixent every two weeks and 5% for placebo).
Detailed results from this trial will be presented at a future medical meeting and data will be submitted to regulatory authorities, starting with the U.S. Food and Drug Administration (FDA) in 4Q 2019. In 2016, the FDA granted Breakthrough Therapy designation for Dupixent for the treatment of moderate-to-severe (12 to 17 years of age) and severe (6 months to 11 years of age) atopic dermatitis. The efficacy and safety of Dupixent in children below the age of 12 has not been reviewed by any regulatory authority.
About the Dupixent Pediatric Trial
The Phase 3, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of Dupixent combined with TCS in children with severe atopic dermatitis. The trial enrolled 367 patients aged 6 to 11 years with severe atopic dermatitis whose disease could not be adequately controlled with topical medications. In total, 92% of these patients suffered from at least one concurrent condition such as allergic rhinitis, asthma and food allergy.
All patients received TCS throughout the trial. Patients were randomized into one of three treatment groups for the 16-week treatment period: Dupixent subcutaneous injection 300 mg every four weeks (with an initial dose of 600 mg); Dupixent 100 mg or 200 mg every two weeks, based on weight (100 mg for <30 kg, 200 mg for ³30 kg), with an initial dose of 200 mg or 400 mg, respectively; and placebo every two or four weeks.
Dupilumab Development Program
In addition to the currently approved indications, Sanofi and Regeneron 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 and atopic dermatitis (6 to 11 years of age, Phase 3), pediatric atopic dermatitis (6 months to 5 years of age, Phase 2/3), eosinophilic esophagitis (Phase 2/3), chronic obstructive pulmonary disease (Phase 3) and food and environmental allergies (Phase 2). Dupilumab is also being studied in combination with REGN3500 (SAR440340), which targets IL-33. These potential uses are investigational and the safety and efficacy have not been evaluated by any regulatory authority.
Dupilumab is being jointly developed by Sanofi and Regeneron under global collaboration agreement.
DUPIXENT is a prescription medicine used:
- to treat people 12 years of age 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 12 years of age.
- with other asthma medicines for the maintenance treatment of moderate-to-severe 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 to treat chronic rhinosinusitis with nasal polyposis 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 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:
- have eye problems
- have a parasitic (helminth) infection
- are taking oral, topical, or inhaled corticosteroid medicines. Do not stop taking your corticosteroid medicines unless instructed by your healthcare provider. This may cause other symptoms that were controlled by the corticosteroid medicine to come back.
- 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. If you are taking asthma medicines, do not change or stop your asthma medicine without talking to your healthcare provider.
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. 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.
Please see accompanying full Prescribing Information including Patient Information.
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents life-transforming medicines for people with serious diseases. Founded and led for 30 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to seven FDA-approved treatments and numerous product candidates in development, all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye disease, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, infectious diseases, pain and rare diseases.
Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune® which produces optimized fully-human antibodies, and 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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