FDA Reviews Dupixent® sBLA for Chronic Spontaneous Urticaria

On November 15, 2024, Regeneron Pharmaceuticals, Inc. and Sanofi announced that the U.S. Food and Drug Administration (FDA) has accepted their resubmission of the supplemental Biologics License Application (sBLA) for Dupixent® (dupilumab). This application seeks approval to treat adults and children aged 12 years and older who suffer from chronic spontaneous urticaria (CSU) that is not adequately managed by H1 antihistamines. The FDA is expected to make a decision by April 18, 2025.

The resubmitted sBLA is based on findings from the LIBERTY-CUPID Phase 3 clinical program, which includes three studies: Study A, Study B, and Study C. The key addition in the resubmitted application is the inclusion of results from Study C, which involved patients with uncontrolled CSU who were already on standard H1 antihistamine treatment. Study C, the second pivotal trial in biologic-naïve patients, successfully met its primary and key secondary endpoints, showing significant reductions in itch and urticaria activity, consistent with the results from Study A.

Safety outcomes across all LIBERTY-CUPID Phase 3 trials align with the known safety profile of Dupixent in its current approved uses. The most common adverse events reported with Dupixent (at a rate of 5% or more) compared to placebo were reactions at the injection site and COVID-19 infections.

CSU is a chronic inflammatory skin condition partially driven by type 2 inflammation, characterized by sudden hives and persistent itching. Standard treatment involves H1 antihistamines, which target H1 receptors to manage urticaria symptoms. However, many patients find that their condition remains uncontrolled despite antihistamine treatment, leaving them with few other treatment options. This significantly impacts their quality of life, as over 300,000 people in the United States experience inadequately managed CSU.

The LIBERTY-CUPID Phase 3 studies for Dupixent in CSU include three trials: Studies A and C included patients with CSU uncontrolled by standard antihistamines, while Study B included those who were not only uncontrolled by standard antihistamines but also refractory or intolerant to omalizumab.

Dupixent has received regulatory approval for CSU in Japan and the United Arab Emirates (UAE) and is currently under review in the European Union based on earlier trial data. Besides Japan and the UAE, the safety and efficacy of Dupixent for CSU have not been fully evaluated by other regulatory authorities.

Developed using Regeneron's VelocImmune® technology, Dupixent is a fully human monoclonal antibody that inhibits IL-4 and IL-13 signaling pathways, crucial drivers of type 2 inflammation. It is not classified as an immunosuppressant. The Dupixent development program has demonstrated significant clinical benefits and a reduction in type 2 inflammation in multiple Phase 3 trials.

Dupixent has global regulatory approval in more than 60 countries for various indications including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis, CSU, and chronic obstructive pulmonary disease across different age groups. Currently, over one million patients worldwide are being treated with Dupixent.

Regeneron's VelocImmune technology involves a genetically engineered mouse platform with a humanized immune system to produce optimized fully human antibodies. This technology has led to the development of several therapeutic antibodies including REGEN-COV®, Libtayo®, Praluent®, Kevzara®, Evkeeza®, Inmazeb®, and Veopoz®.

Dupilumab is being co-developed by Regeneron and Sanofi under a global collaboration. It has been evaluated in more than 60 clinical trials involving over 10,000 patients with various chronic diseases driven in part by type 2 inflammation.

In addition to its current approved uses, Regeneron and Sanofi are exploring Dupilumab’s potential in treating a wide range of type 2 inflammation-driven or allergic diseases in Phase 3 trials, including chronic pruritus of unknown origin and bullous pemphigoid. These potential applications are still under clinical investigation, and their safety and efficacy have not yet been fully assessed by any regulatory authority.

Regeneron is a leading biotechnology company focused on developing life-transforming medicines. The company leverages advanced technologies like VelociSuite to innovate and accelerate drug development, aiming to provide treatments for a wide range of serious diseases.