The FDA has accepted for review the resubmitted supplemental Biologics License Application (sBLA) for dupilumab (Dupixent; Sanofi, Regeneron) for the treatment of chronic spontaneous urticaria (CSU) in adult and pediatric patients 12 years and older whose disease is not adequately controlled with histamine-1 (H1) antihistamine treatment. The target action date for the FDA decision is April 18, 2025.
Dupilumab, a fully human monoclonal antibody, inhibits the signaling of the interleukin (IL)-4 and IL-13 pathways, key drivers of type 2 inflammation. It is already approved in over 60 countries for various indications, including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis, CSU, and chronic obstructive pulmonary disease. It is currently in phase 3 trials for chronic pruritus of unknown origin and bullous pemphigoid.
LIBERTY-CUPID Phase 3 Trial Program
The resubmitted sBLA is supported by data from the LIBERTY-CUPID phase 3 clinical trial program (NCT04180488), which includes three trials: study A, study B, and study C. The sBLA incorporates results from study C, a randomized, double-blind, placebo-controlled trial involving 151 patients aged 6 years and older with uncontrolled CSU on standard-of-care antihistamines who were omalizumab-naïve. Patients were randomized to receive subcutaneous injections of either dupilumab (n = 74) or placebo (n = 77) as an add-on to their non-sedating H1 antihistamines.
The primary endpoint for study C was the change in itch severity from baseline to week 24, measured by the weekly itch severity score (ISS7) on a 0 to 21 scale. Secondary endpoints at 24 weeks included changes from baseline in itch and hives, the proportion of patients achieving well-controlled disease status, and complete response.
Significant Results
Dupilumab met both its primary and key secondary endpoints, confirming results from study A. Patients treated with dupilumab experienced significant reductions in itch and hive activity compared to placebo. Specifically, dupilumab-treated patients reported ISS7 score reductions of 8.64, while those receiving placebo experienced a reduction of 6.10 (P = .02). Itch and hive activity scores were reduced by 15.86 and 11.21 in the dupilumab and placebo groups, respectively (P = .02). Furthermore, 41% of patients in the dupilumab group achieved well-controlled disease status compared to 23% in the placebo group (P = .005), and more patients achieved a complete response (30% vs 18%; P = .02).
Safety Profile
The safety results from the LIBERTY-CUPID phase 3 trials were consistent with the known safety profile of dupilumab in its approved indications. Adverse events (AEs) were more common with dupilumab compared to placebo, including injection site reactions (12% vs 4%), accidental overdose (7% vs 3%), and COVID-19 infection (8% vs 5%).
Expert Commentary
"CSU is an inflammatory skin condition that affects patients with unpredictable episodes of intense itching and hives, often severely impacting their daily lives," said Thomas B. Casale, MD, professor of internal medicine, Morsani College of Medicine at the University of South Florida. "These data confirm results seen in the previous study A and reinforce the potential of [dupilumab] to significantly alleviate symptoms for patients, helping them to better control this challenging disease."
