The U.S. Food and Drug Administration (FDA) has accepted for review the resubmission of the supplemental Biologics License Application (sBLA) for Dupixent (dupilumab) for the treatment of adults and pediatric patients aged 12 years and older with chronic spontaneous urticaria (CSU) whose disease is not adequately controlled with H1 antihistamine treatment. The target action date for the FDA decision is April 18, 2025.
The resubmitted sBLA is backed by data from the multi-study LIBERTY-CUPID phase 3 clinical program (Study A, Study B, and Study C) evaluating Dupixent in CSU. The submission includes results from Study C, which was conducted in patients with uncontrolled CSU despite treatment with standard-of-care antihistamines. Study C, the second LIBERTY-CUPID pivotal study in biologic-naïve patients, met its primary and key secondary endpoints, confirming results observed in the previous Study A. The data demonstrated that Dupixent significantly reduced both itch and urticaria activity, addressing key symptoms of the condition.
Efficacy and Safety Profile
The LIBERTY-CUPID phase 3 studies' safety results were generally consistent with Dupixent's established safety profile across its approved indications. Adverse events more commonly observed with Dupixent (=5%) compared to placebo included injection site reactions and COVID-19 infection. These findings support the overall tolerability of Dupixent in the CSU patient population.
Understanding Chronic Spontaneous Urticaria
Chronic Spontaneous Urticaria (CSU) is a chronic inflammatory skin disease driven in part by type-2 inflammation, leading to sudden and debilitating hives and recurring itch. The condition is typically managed with H1 antihistamines, which target H1 receptors on cells to control urticaria symptoms. However, many patients' disease remains uncontrolled despite antihistamine treatment, leaving them with limited alternative treatment options. These individuals continue to experience debilitating symptoms that significantly impact their quality of life. More than 300,000 people in the US suffer from CSU that is inadequately controlled by antihistamines.
Dupixent's Mechanism of Action
Dupixent (dupilumab) is a fully human monoclonal antibody that inhibits the signaling of the IL-4 and IL-13 pathways and is not an immunosuppressant. The Dupixent development program has demonstrated significant clinical benefit and a decrease in type-2 inflammation in phase 3 studies, establishing that IL-4 and IL-13 are two of the key and central drivers of type-2 inflammation that play a major role in multiple related and often co-morbid diseases.
Global Regulatory Landscape
Dupixent has been approved for CSU in Japan and the United Arab Emirates (UAE) and is also under regulatory review in the EU based on earlier study readouts. Outside of Japan and the UAE, the safety and efficacy of Dupixent for CSU has not been fully evaluated by any regulatory authority.
Ongoing Research and Development
Sanofi and Regeneron are jointly developing dupilumab under a global collaboration agreement. To date, dupilumab has been studied across more than 60 clinical studies involving more than 10,000 patients with various chronic diseases driven in part by type-2 inflammation. In addition to the currently approved indications, Sanofi and Regeneron are studying dupilumab in a broad range of diseases driven in part by type-2 inflammation or other allergic processes in phase 3 studies, including chronic pruritus of unknown origin 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.
