Dupilumab Proves Effective in Chronic Spontaneous Urticaria

BOSTON — Add-on dupilumab (Dupixent) significantly reduced itching and urticaria in patients with chronic spontaneous urticaria (CSU) whose symptoms were uncontrolled with H1-antihistamine therapy.

The phase III LIBERTY-CUPID study C showed that among children and adults randomized to receive either dupilumab or placebo added to standard-of-care (SoC) H1 antihistamines, those receiving dupilumab experienced an 8.64-point reduction in itch severity versus a 6.10-point reduction with placebo (-2.5 difference, P=0.02) from baseline to week 24, reported Thomas B. Casale, MD, of the University of South Florida in Tampa. Itch severity was measured on the 21-point Itch Severity Score over 7 days (ISS7; 21=severe itching every day of the week).

In addition, treatment with dupilumab resulted in a 15.86-point reduction in urticaria activity (itch and hive) severity from baseline versus an 11.21-point reduction with placebo (-4.7 difference, P=0.02), based on the 42-point Urticaria Activity Score over 7 days (UAS7; scores 28-42 over 7 days=severe urticaria).

In a presentation at the American College of Allergy, Asthma & Immunology annual meeting, Casale highlighted that the data at week 24 showed that almost twice as many patients had a UAS7 score of ≤6 (40.5% with dupilumab vs 23.5% with placebo), “which means well-controlled urticaria. And if you look even further at patients who had a UAS7 score of 0 — that is complete remission — at 24 weeks you’re looking at about 30% with dupilumab versus 18% with placeb0. So, it’s very reassuring data that the primary and secondary endpoints are being achieved.”

Individuals with CSU develop hives and/or angioedema, can experience intense itching, and have a low quality of life, Casale explained, with about half of patients unresponsive to SoC H1 antihistamines.

LIBERTY-CUPID study C is designed to replicate LIBERTY-CUPID study A, in which dupilumab was shown to reduce itch and hive severity in omalizumab (Xolair)-naive patients. Study A supported the approval of dupilumab in Japan for the treatment of CSU in people ages 12 years and older whose disease is not adequately controlled with existing therapy.

Study C will support regulatory resubmission in the U.S. in response to an FDA Complete Response Letter requesting additional efficacy data. If approved, dupilumab would be the first targeted therapy for CSU in a decade, according to developer Sanofi.

The study was a placebo-controlled, double-blind, 24-week phase III trial that included 151 patients, ages 6 years or older, who were randomized to receive add-on dupilumab at 300 mg for adults and adolescents ≥60 kg, or 200 mg for adolescents

According to Casale, the study’s demographics “were similar to almost every urticaria study” where the predominant population was female (70%), with a median age of about 45, and a BMI 27. The baseline ISS7 score was 15.1, and baseline USA7 score was 28.3. About half of patients were receiving a standard dose of antihistamines, and the other half a 2-to-4-fold standard dose.

Safety was generally consistent with the known safety profile of dupilumab. Treatment-emergent adverse events (TEAEs) were the same for both groups (53%), with nasopharyngitis being the most common (8.1% with dupilumab and 5.2% with placebo). Injection site erythema was seen in 5.4% of patients in the dupilumab group. Severe TEAEs occurred in three patients in the dupilumab group and one in the placebo group, while serious TEAEs occurred in five patients in the dupilumab group and one on placebo.