Positive results from the Phase 3 LIBERTY-CUPID Study C reveal that dupilumab (Dupixent) significantly reduces itch symptoms and urticaria activity in biologic-naive patients with uncontrolled chronic spontaneous urticaria (CSU) receiving background antihistamine therapy. The findings, presented at the American College of Allergy, Asthma and Immunology (ACAAI) 2024 Annual Scientific Meeting, highlight dupilumab's potential to improve disease control in patients with CSU.
Impact on CSU Symptoms
Chronic spontaneous urticaria, characterized by unpredictable episodes of intense itching and hives, affects patients' daily lives significantly. CSU is often driven by type-2 inflammation, leading to sudden and debilitating hives and persistent itch. Despite the use of histamine-1 (H1) antihistamines, a substantial number of patients, exceeding 300,000 in the US alone, continue to experience inadequate control of their CSU.
Mechanism of Action and Clinical Development
Dupilumab, a fully human monoclonal antibody, functions by inhibiting the signaling of the IL-4 and IL-13 pathways. Its clinical development program has demonstrated notable clinical benefits and a reduction in type-2 inflammation in Phase 3 studies, establishing IL-4 and IL-13 as key drivers of type-2 inflammation.
LIBERTY-CUPID Study Design and Results
The Phase 3 LIBERTY-CUPID trial program evaluated dupilumab for CSU across three studies (Study A, Study B, and Study C). Study C was a randomized, double-blind, placebo-controlled trial involving 151 biologic-naive patients aged ≥6 years with CSU. Patients were administered dupilumab as an add-on to antihistamines versus antihistamines alone.
The primary endpoint in Study C was the change from baseline in itch at 24 weeks, measured using the weekly itch severity score (scale, 0–21). Secondary endpoints at 24 weeks included the change from baseline in itch and hives, measured by the weekly urticaria activity score (UAS7) (scale, 0-42), the proportion of patients achieving well-controlled disease status (UAS7 ≤6), and complete response (UAS7, 0).
Results showed that dupilumab achieved significant improvements in the itch severity score compared to placebo (8.64 vs. 6.10 point baseline reduction; P = .02). Dupilumab also outperformed placebo on the UAS7 (15.86 vs. 11.21 point baseline reduction; P = .02) and in the achievement of well-controlled disease status (UAS7 ≤6; 41% vs. 23%; P = .005) or complete response (UAS7, 0; 30% vs. 18%; P = .02).
Safety Profile
The safety profile of dupilumab in Study C was consistent with its known safety profile in dermatological indications approved by the FDA. The rates of treatment-emergent adverse events (TEAEs) were 53% for both dupilumab and placebo. Common TEAEs with dupilumab (≥5%) included injection site reactions (12% vs. 4%), accidental overdose (7% vs. 3%), and COVID-19 infection (8% vs. 5%).
According to Dr. Thomas B. Casale, a professor of internal medicine at the 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."
