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The indication is for patients 12 and older with chronic spontaneous urticaria (CSU) whose disease is not adequately controlled with H1 antihistamine treatment.
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The FDA accepted for review the resubmission of the supplemental biologics license (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. According to experts, the target action date for the FDA decision is April 18, 2025.1
Dupilumab is a fully human monoclonal antibody that inhibits the signaling of the interleukin (IL)-4 and IL-13 pathways, which are 2 of the key drivers of type 2 inflammation that play a major role in multiple related—and often comorbid—diseases. It is not an immunosuppressant. Further, dupilumab has received regulatory approvals in more than 60 countries as well as for indications within atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis, chronic spontaneous urticaria, and chronic obstructive pulmonary disease in different age groups. The treatment is currently undergoing evaluation in phase 3 clinical trials for its potential use in chronic pruritus of unknown origin and bullous pemphigoid.1,2
CSU is a chronic inflammatory skin disease that is driven by type-2 inflammation, which causes sudden and often debilitating hives and recurring itch. CSU is often treated with H1 antihistamines; however, the disease remains uncontrolled despite antihistamine treatment in many patients.1,2
The resubmitted sBLA comes after supportive data from the LIBERTY-CUPID phase 3 clinical trial program (NCT04180488). The program consists of 3 phase 3 trials—study A, study B, and study C—in which dupilumab is evaluated for the treatment of CSU. The sBLA adds results from study C, a randomized, double-blind, placebo-controlled trial which enrolled patients 6 years and older with uncontrolled CSU who were on standard of care antihistamines, not previously treated with a biologic, and were omalizumab (Xolair; Genentech)-naïve. A total of 151 patients were randomly assigned to receive either subcutaneous injections of dupilumab (n = 74) or placebo (n = 77) as an add-on treatment to their no-sedating H1 antihistamines.2,3
Trial Name: Dupilumab for the Treatment of Chronic Spontaneous Urticaria in Patients Who Remain Symptomatic Despite the Use of H1 Antihistamine and Who Are naïve to, Intolerant of, or Incomplete Responders to Omalizumab (LIBERTY-CSU CUPID)
ClinicalTrials.gov ID: NCT04180488
Sponsor: Sanofi
Completion Date (Estimated): October 24, 2024
The primary end point for study C was change in itch severity from baseline to week 24, which was measured by a weekly itch severity score (ISS7) on a 0 to 21 scale. Secondary end points measured at the 24-week included the change from baseline in itch and hives, proportion of patients who achieved well-controlled disease status, and complete response.2,3
According to the findings, dupilumab met both its primary and key secondary end points, confirming results demonstrated from study A. Dupilumab was shown to significantly reduce itch and activity of itch and hives compared with placebo. Patients on dupilumab reported ISS7 score reductions of 8.64, whereas those receiving placebo experienced a reduction of 6.10 (P = .02). In addition, itch and hive activity scores were reduced by 15.86 and 11.21 in the dupilumab and placebo groups, respectively (P = .02). Patients in the dupilumab group were also observed to have more improvements in well-controlled disease status (41%) compared with placebo (23%; P = .005). More patients achieved a complete response in the dupilumab group. (30% vs 18%; P = .02).1-3
Further, safety results in all LIBERTY-CUPID phase 3 trials were generally consistent with the known safety profile of dupilumab in its approved indications. Adverse events (AEs) were more common with dupilumab compared with placebo, and consisted of injection site reactions (12% vs 4%), accidental overdose (7% vs 3%), and COVID-19 infection (8% vs 5%).1,2
“CSU is an inflammatory skin condition that affects patients with unpredictable episodes of intense itching and hives, often severely impacting their daily lives. 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,” Thomas B. Casale, MD, professor of internal medicine, Morsani College of Medicine at the University of South Florida, said in a news release.2
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