- Children treated with Dupixent and topical corticosteroids (TCS) achieved clearer skin, experienced significantly improved overall disease severity and significantly reduced itch compared to TCS alone at week 16 in a Phase 3 trial
- Long-term safety data from a 52-week open-label extension trial in this age group reinforce the well-established safety profile of Dupixent observed across all other approved age groups
- Dupixent is the first and only biologic medicine approved to treat moderate-to-severe atopic dermatitis from infancy through adulthood
Regeneron Pharmaceuticals, Inc. and Sanofi today announced that the U.S. Food and Drug Administration (FDA) has approved Dupixent® (dupilumab) for children aged 6 months to 5 years with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Regulatory filings for this age group are underway by the European Medicines Agency and regulatory authorities in additional countries.
API – Dupilumab
Description : Dupilumab, sold under the brand name Dupixent, is a monoclonal antibody blocking interleukin 4 and interleukin 13, used for allergic diseases such as eczema, asthma and nasal polyps which result in chronic sinusitis. It is also used for the treatment of eosinophilic esophagitis.
DUPIXENT is a prescription medicine used:
- to treat adults and children 6 months 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 6 months of age.
- with other asthma medicines for the maintenance treatment of moderate-to-severe eosinophilic or oral steroid dependent asthma in adults and children 6 years of age 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 6 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.
- to treat adults and children 12 years of age and older, who weigh at least 88 pounds (40 kg), with eosinophilic esophagitis (EoE). It is not known if DUPIXENT is safe and effective in children with eosinophilic esophagitis under 12 years of age and who weigh at least 88 pounds (40 kg).
DUPIXENT can cause serious side effects, including:
- Allergic reactions. DUPIXENT can cause allergic reactions that can sometimes be severe. Stop using DUPIXENT and tell your healthcare provider or get emergency help right away if you get any of the following signs or symptoms: breathing problems or wheezing, swelling of the face, lips, mouth, tongue or throat, fainting, dizziness, feeling lightheaded, fast pulse, fever, hives, joint pain, general ill feeling, itching, skin rash, swollen lymph nodes, nausea or vomiting, or cramps in your stomach-area.
- Eye problems. Tell your healthcare provider if you have any new or worsening eye problems, including eye pain or changes in vision, such as blurred vision. Your healthcare provider may send you to an ophthalmologist for an exam if needed.
- 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, chest pain, worsening shortness of breath, a feeling of pins and needles or numbness of your arms or legs, or persistent fever.
- Joint aches and pain. Some people who use DUPIXENT have had trouble walking or moving due to their joint symptoms, and in some cases needed to be hospitalized. Tell your healthcare provider about any new or worsening joint symptoms. Your healthcare provider may stop DUPIXENT if you develop joint symptoms.
The most common side effects include:
- Atopic dermatitis: injection site reactions, eye and eyelid inflammation, including redness, swelling, and itching, sometimes with blurred vision, cold sores in your mouth or on your lips, and high count of a certain white blood cell (eosinophilia).
- Asthma: injection site reactions, pain in the throat (oropharyngeal pain), high count of a certain white blood cell (eosinophilia), and parasitic (helminth) infections.
- Chronic rhinosinusitis with nasal polyposis: injection site reactions, eye and eyelid inflammation, including redness, swelling, and itching, sometimes with blurred vision, high count of a certain white blood cell (eosinophilia), trouble sleeping (insomnia), toothache, gastritis, and joint pain (arthralgia).
- Eosinophilic esophagitis: injection site reactions, upper respiratory tract infections, cold sores in your mouth or lips, and joint pain (arthralgia).
Mechanism of action
Dupilumab binds to the alpha subunit of the interleukin-4 receptor (IL-4Rα), making it a receptor antagonist. Through blockade of IL-4Rα, dupilumab modulates signaling of both the interleukin 4 and interleukin 13 pathways
Dupilumab Development Program
Dupilumab is being jointly developed by Regeneron and Sanofi under a global collaboration agreement. To date, dupilumab has been studied across more than 60 clinical trials involving more than 10,000 patients with various chronic diseases driven in part by type 2 inflammation.
In addition to the currently approved indications, Regeneron and Sanofi are studying dupilumab in a broad range of diseases driven by type 2 inflammation or other allergic processes in Phase 3 trials, including prurigo nodularis, pediatric eosinophilic esophagitis, hand and foot atopic dermatitis, chronic inducible urticaria-cold, chronic spontaneous urticaria, chronic pruritis of unknown origin, chronic obstructive pulmonary disease with evidence of type 2 inflammation, chronic rhinosinusitis without nasal polyposis, allergic fungal rhinosinusitis, allergic bronchopulmonary aspergillosis and bullous pemphigoid. 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.
“Moderate-to-severe atopic dermatitis in babies and young children is more than just a rash – the intense itch can make them scratch uncontrollably throughout the day and night and cause their skin to crack and bleed,” said Julie Block, President and Chief Executive Officer at National Eczema Association. “Caregivers do their best to manage skincare routines multiple times a day, but for many, topical treatments are not enough. We’re pleased to see how scientific innovation and research continues to address unmet needs for the atopic dermatitis community, and we’re hopeful for the positive impact Dupixent can have for these children and their families.”
The FDA evaluated Dupixent under Priority Review, which is reserved for medicines that represent potentially significant improvements in efficacy or safety in treating serious conditions. The approval is based on data that include a Phase 3 trial evaluating Dupixent every four weeks (200 mg or 300 mg, based on body weight) plus low-potency topical corticosteroids (TCS) or TCS alone. The trial met the primary and all secondary endpoints. At 16 weeks, patients who received Dupixent with TCS experienced the following, compared to TCS alone (placebo):
- 28% achieved clear or almost-clear skin compared to 4% with placebo, the primary endpoint.
- 53% achieved 75% or greater improvement in overall disease severity from baseline compared to 11% with placebo, the co-primary endpoint outside of the U.S.
- 48% achieved clinically meaningful reduction in itch compared to 9% with placebo.
The safety profile of Dupixent observed through 16 weeks in children aged 6 months to 5 years was similar to the safety profile in patients 6 years and older with atopic dermatitis. The long-term safety profile of Dupixent in children aged 6 months to 5 years through 52 weeks was also similar to the safety profile observed in the pivotal trial and consistent with what was observed in older patients with atopic dermatitis. Hand-foot-and-mouth disease and skin papilloma were, respectively, reported in 5% and 2% of Dupixent patients aged 6 months to 5 years, and none of these cases led to treatment discontinuation.
“Young children with moderate-to-severe atopic dermatitis are a significantly underserved population of patients, who spend vulnerable years of their lives suffering through the relentless and far-reaching effects of this chronic disease,” said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron, and a principal inventor of Dupixent. “Dupixent has changed the atopic dermatitis treatment paradigm – significantly clearing skin and reducing itch – by targeting an underlying cause of this disease without broadly suppressing the immune system. Today’s approval brings the proven efficacy and, importantly, well-established safety profile of Dupixent to these young children, making it the first of its kind to be approved for any U.S. patient aged six months or older living with this debilitating disease.”
“Until today, treatment options in the U.S. for infants and children under the age of 6 suffering from moderate-to-severe atopic dermatitis have been limited to topical steroids – which may be associated with significant safety risks when used long-term. This has left patients and their caregivers in desperate need of medicines that can better address the chronic, long-term nature of the disease,” Naimish Patel, M.D, Senior Vice President, Head of Global Development, Immunology and Inflammation at Sanofi. “These young people, and their families, often struggle to cope with the significant impact itch can have not only on the body, but on many other facets of daily life. This approval means that Dupixent, with its well-established safety and efficacy profile, is now available to some of the youngest people living with this disease.”
About Atopic Dermatitis
Atopic dermatitis is a chronic type 2 inflammatory skin disease. Eighty-five to ninety percent of patients first develop symptoms before 5 years of age, which can often continue through adulthood. Symptoms include intense, persistent itch and skin lesions that cover much of the body, resulting in skin dryness, cracking, pain, redness or darkening, and crusting and oozing. In the U.S., more than 75,000 children aged 5 years and younger have uncontrolled moderate-to-severe disease and are most in need of new treatment options. Moderate-to-severe atopic dermatitis may also significantly impact the quality of life of a young child and their caregivers.
Regeneron is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for nearly 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous FDA-approved treatments and product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, pain, hematologic conditions, infectious diseases and rare diseases.
We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across some 100 countries, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions.