Positive phase 3 data from the LIBERTY-CUPID Study C evaluating Dupixent (dupilumab) in patients with uncontrolled chronic spontaneous urticaria (CSU) showed significant reductions in itch and hive activity, with a notable proportion of patients achieving well-controlled disease status compared to placebo. The findings, presented at the American College of Allergy, Asthma and Immunology (ACAAI) 2024 Annual Scientific Meeting, support a planned US regulatory resubmission by the end of the year. If approved, Dupixent would be the first new targeted treatment for CSU in over 10 years.
The study enrolled 151 adults and children who were biologic-naive, meaning they had not previously been treated with omalizumab, and whose CSU was inadequately controlled by H1 antihistamines. Participants were randomized to receive Dupixent or placebo in addition to their antihistamine regimen. At 24 weeks, Dupixent demonstrated statistically significant improvements across key endpoints.
Key Findings from LIBERTY-CUPID Study C
- Itch Severity: Dupixent-treated patients experienced an 8.64-point reduction in itch severity score from baseline, compared to a 6.10-point reduction in the placebo group (p=0.02).
- Urticaria Activity: The urticaria activity score, measuring both itch and hives, decreased by 15.86 points in the Dupixent arm versus 11.21 points in the placebo arm (p=0.02).
- Disease Control: 41% of Dupixent patients achieved well-controlled disease status (urticaria activity score ≤6), compared to only 23% of placebo patients (p=0.005).
- Complete Response: 30% of Dupixent patients achieved complete response (urticaria activity score=0), versus 18% of placebo patients (p=0.02).
Expert Commentary
"Chronic spontaneous urticaria is an inflammatory skin condition that affects patients with unpredictable episodes of intense itching and hives, often severely impacting their daily lives," said Dr. Thomas B. Casale, Professor of Internal Medicine at the University of South Florida's Morsani College of Medicine. "These data confirm results seen in the previous Study A and reinforce the potential of Dupixent to significantly alleviate symptoms for patients, helping them to better control this challenging disease."
Safety Profile
The safety profile of Dupixent in Study C was consistent with its known safety profile in approved dermatological indications. Overall rates of treatment-emergent adverse events were similar between the Dupixent and placebo groups (53% each). Adverse events more commonly observed with Dupixent included injection site reactions (12% vs. 4% with placebo), accidental overdose (7% vs. 3%), and COVID-19 infection (8% vs. 5%).
About Chronic Spontaneous Urticaria
Chronic spontaneous urticaria is characterized by sudden and debilitating hives and persistent itch, driven by type-2 inflammation. While H1 antihistamines are commonly used, many patients remain symptomatic, highlighting the need for alternative treatment options. In the US, over 300,000 people suffer from CSU that is inadequately controlled by antihistamines.
Dupixent's Mechanism of Action
Dupixent is a fully human monoclonal antibody that inhibits the signaling of the IL-4 and IL-13 pathways, key drivers of type-2 inflammation. It is not an immunosuppressant. Dupixent has already been approved for CSU in Japan and the United Arab Emirates, and is under regulatory review in the European Union. It is also approved for other indications, including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis, and chronic obstructive pulmonary disease in different age populations.
Ongoing Development
Dupixent is being jointly developed by Sanofi and Regeneron under a global collaboration agreement. It is currently being investigated in phase 3 studies for chronic pruritus of unknown origin and bullous pemphigoid.
