FDA Accepts Dupilumab Application for Chronic Spontaneous Urticaria Treatment
核心洞察
The FDA has accepted the sBLA for dupilumab for treating chronic spontaneous urticaria (搜索) (CSU) in adults and children aged 12 years and older.
The target action date for potential approval of dupilumab for CSU is set for April 18, 2025, marking a potential first targeted therapy in a decade.
The application is supported by data from the LIBERTY-CUPID phase 3 clinical program, demonstrating significant improvements in itch and hives.
The FDA has accepted the resubmitted supplemental Biologics License Application (sBLA) for dupilumab (Dupixent; Regeneron and Sanofi) for the treatment of chronic spontaneous urticaria (搜索) (CSU) in adults and pediatric patients aged 12 years and older. According to a press release from Regeneron, the IL-4 (搜索) and IL-13 (搜索) inhibitor is intended for CSU patients whose condition is not adequately controlled with H1 antihistamine treatment.
With the sBLA accepted, the FDA has set a target action date of April 18, 2025, for potential approval. If approved, dupilumab would be the first targeted therapy for CSU in a decade, according to Regeneron and Sanofi.
The resubmitted sBLA was supported by data from the LIBERTY-CUPID phase 3 clinical program, which included Study A, Study B, and Study C. The sBLA incorporated results from Study C, conducted in patients with uncontrolled CSU on standard-of-care antihistamines. This study met primary and key secondary endpoints, confirming results observed in Study A.
LIBERTY-CUPID Trial Results
In Study A and Study B—phase 3, randomized, placebo-controlled, double-blind trials comparing dupilumab with placebo in symptomatic CSU patients despite H1-AH—the treatment met the primary and all key secondary outcomes. Study A featured omalizumab-naive patients (n = 138) aged 6 years or older, while Study B featured omalizumab-intolerant/incomplete responders (n = 108) aged 12 years and older. The primary endpoint was the change from baseline over 7 days in the Urticaria Activity Score (UAS7) or Itch Severity Score (ISS7) at week 24.
In Study A, UAS7 and ISS7 improved with dupilumab compared to placebo (difference -8.5 [95% CI, -13.2 to -3.9; P = .0003] and -4.2 [95% CI, -6.6 to -1.8; P = .0005]), according to results published in The Journal of Allergy and Clinical Immunology.
In Study B (tested at a = 0.043 after interim analysis), UAS7 improved (difference -5.8 [95% CI, -11.4 to -0.3; P = .0390]), with a numerical trend in ISS7 (difference -2.9 [95% CI, -5.7 to -0.07; nominal P = .0449, not significant]), according to study authors. Across each study, pooled safety data revealed consistency between dupilumab and placebo, aligning with the "known dupilumab safety profile," per study results.
Study C Findings
Among biologic-naive CSU patients receiving background therapy with antihistamines, dupilumab met the primary and key secondary outcomes in the Study C phase 3 trial. This portion of the LIBERTY-CUPID clinical program enrolled 151 children and adults randomized to receive dupilumab (n = 74) or placebo (n = 77) added to standard-of-care H1 antihistamines.
According to results at the 24-week mark, dupilumab demonstrated an 8.64-point reduction in itch severity from baseline, compared to a 6.10-point reduction with placebo (P = .02), as well as a 15.86-point reduction in urticaria activity severity versus an 11.21-point reduction with placebo (P = .02).
In addition, "30% of Dupixent-treated patients reported no urticaria (complete response), compared to 18% of those on placebo (P = .02)," Sanofi stated in a September 11, 2024, press release.