The FDA has accepted the resubmitted supplemental Biologics License Application (sBLA) for dupilumab (Dupixent; Regeneron and Sanofi) for the treatment of chronic spontaneous urticaria (CSU) in adults and pediatric patients aged 12 years and older. According to a press release from Regeneron, the IL-4 and IL-13 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.
