Regeneron Pharmaceuticals, Inc. and Sanofi today announced a pivotal Phase 3 trial evaluating Dupixent (dupilumab) in patients with moderate-to-severe chronic spontaneous urticaria (CSU) met its primary and all key secondary endpoints at 24 weeks. Adding Dupixent to standard-of-care antihistamines significantly reduced itch and hives for biologic-naïve patients, compared to antihistamines alone in Study A, the first of two trials of the LIBERTY-CUPID clinical program.
"This is the first Phase 3 trial to show that by targeting IL-4 and IL-13, Dupixent can address the debilitating symptoms of chronic spontaneous urticaria like persistent itch and hives when standard-of-care antihistamines cannot sufficiently control the disease," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron. "These data add to the increasing body of evidence that Dupixent can reduce the disease burden of a diverse range of dermatologic, respiratory and gastrointestinal diseases. By early 2022, we look forward to reporting results from a second trial in patients who were unable to control their chronic spontaneous urticaria with another biologic medicine, as well as other trial results in additional dermatologic diseases."
CSU is a chronic inflammatory skin disease characterized by the sudden onset of hives on the skin and/or swelling deep under the skin. Despite standard-of-care treatment, people with CSU often experience symptoms including a persistent itch or burning sensation, which can be debilitating and significantly impact quality of life. Swelling often occurs on the face, hands and feet, and can also affect the throat and upper airways. CSU is typically treated with antihistamines but the disease remains uncontrolled for up to 50% of patients who have limited available treatment options. CSU is the fifth disease for which Dupixent has positive Phase 3 data including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis and eosinophilic esophagitis (EoE, investigational).
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"The chronic nature of CSU, coupled with intense itch, causes both a physical and emotional burden on people who have not found an effective treatment," said John Reed, M.D., Ph.D., Global Head of Research and Development at Sanofi. "This is the fifth inflammatory disease in which Dupixent has demonstrated a significant improvement in symptoms and disease manifestations in Phase 3 pivotal studies. The success of this trial underscores the agility of our clinical operations team considering the pandemic conditions and underscores our ability to deliver on an aggressive timeline for addressing a significant unmet need for this patient population."
In the trial (n=138), adding Dupixent to standard-of-care antihistamines nearly doubled the reduction in itch and urticaria activity compared to standard-of-care alone (placebo) with continuous improvement out to 24 weeks. Patients experienced a:
The trial demonstrated safety results similar to the known safety profile of Dupixent in its approved indications. For the 24-week treatment period, the occurrence of treatment emergent adverse events were generally similar between the Dupixent and placebo groups (50% Dupixent, 59% placebo). The most common adverse events were injection site reactions (11% Dupixent, 13% placebo).
The potential use of Dupixent in CSU and EoE is currently under clinical development, and the safety and efficacy have not been fully evaluated by any regulatory authority.
About the Trial
Study A of the Phase 3 randomized, double-blind, placebo-controlled LIBERTY-CUPID clinical program evaluated the efficacy and safety of Dupixent as an add-on therapy to standard-of-care antihistamines compared to antihistamines alone in 138 patients aged 6 years and older with CSU who remained symptomatic despite antihistamine use and were not previously treated with omalizumab.
The primary endpoints assessed the change from baseline in itch (measured by the weekly itch severity score [ISS7]) and the change from baseline in itch and hives (measured by the weekly urticaria activity score [UAS7]) at 24 weeks.
Study B of this clinical program is ongoing to evaluate Dupixent in adults and adolescents who remain symptomatic despite standard-of-care treatment and are intolerant or incomplete responders to omalizumab. The trial is expected to read out in the first half of 2022. Sanofi and Regeneron plan to begin regulatory submissions in 2022. In addition to CSU, Regeneron and Sanofi are also studying Dupixent in chronic inducible urticaria triggered by cold (LIBERTY-CINDU CUrIADS program) in an ongoing Phase 3 trial.
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 asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), atopic dermatitis and eosinophilic esophagitis and may contribute to CSU.
In the U.S. and Europe, Dupixent is approved for patients 6 years and older with moderate-to-severe atopic dermatitis, patients 12 years and older with moderate-to-severe asthma, and in adults with uncontrolled CRSwNP. 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.
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 multiple antibodies including Dupixent, Libtayo (cemiplimab-rwlc), Praluent (alirocumab), Kevzara (sarilumab), Evkeeza (evinacumab-dgnb) and InmazebTM (atoltivimab, maftivimab, and odesivimab-ebgn).
Dupilumab Development Program
To date, Dupixent has been studied across 50 clinical trials involving more than 10,000 patients with various chronic diseases driven 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.
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.
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: Jul 29, 2021
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