Dupilumab Reduces Itch in Chronic Spontaneous Urticaria in Phase 3 Data

Thomas B. Casale, MD

Credit: LinkedIn

Positive data from Phase 3 LIBERTY-CUPID Study C supported the role of investigational dupilumab (Dupixent) for biologic-naive patients with uncontrolled chronic spontaneous urticaria (CSU) who receive background antihistamine therapy.¹

These results, presented in a late-breaking oral presentation at the American College of Allergy, Asthma and Immunology (ACAAI) 2024 Annual Scientific Meeting, showed dupilumab significantly reduced itch symptoms and urticaria activity, with a higher proportion of patients treated with dupilumab achieving well-controlled disease status versus placebo.

“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 Thomas B. Casale, MD, a professor of internal medicine at the Morsani College of Medicine at the University of South Florida.¹

CSU is often driven by type-2 inflammation causing sudden and debilitating hives and persistent itch.² Despite histamine-1 (H1) antihistamine use, CSU can remain uncontrolled—with limited treatment options, more than 300,000 people in the US experience inadequate control of CSU.

Dupilumab is a fully human monoclonal antibody inhibiting the signaling of the IL4 and IL13 pathways.³ The drug’s clinical development program has demonstrated notable clinical benefit and a decrease in type-2 inflammation in Phase 3 studies, establishing IL4 and IL3 as key drivers of type-2 inflammation.

The Phase 3 LIBERTY-CUPID trial program evaluated dupilumab for CSU in Study A, Study B, and Study C. Study C was a randomized, double-blind, placebo-controlled clinical trial assessing dupilumab as an add-on to antihistamines versus antihistamines alone in 151 biologic-naive patents aged ≥6 years with CSU.

A primary endpoint in Study C measured the change from baseline in itch at 24 weeks using the weekly itch severity score (scale, 0–21). Secondary endpoints at 24 weeks, measured by the weekly urticaria activity score (UAS7), involved the change from baseline in itch and hives (scale, 0-42), the proportion of patients achieving well-controlled disease status (scale, ≤6), and complete response (scale, 0).

Overall, 151 children and adults were randomized to receive dupilumab (n = 74) or placebo (n = 77) in addition to standard-of-care H1 antihistamines. At the 24-week mark, dupilumab achieved significant improvements in the itch severity score versus placebo (8.64 vs. 6.10 point baseline reduction; P = .02).

Dupilumab also outperformed placebo on the UAS7 (15.86 vs. 11.21 point baseline reduction; P = .02) and the achievement of well-controlled disease status (UAS7, ≤6; 41% vs. 23%; P = .005) or complete response (UAS7, 0; 30% vs. 18%; P = .02).

Safety results in Study C remained in line with the known safety profile of dupilumab in dermatological indications approved by the US Food and Drug Administration (FDA). The rates of treatment-emergent adverse events (TEAEs) were 53% for both dupilumab and placebo; common TEAEs with dupilumab (≥5%) included injection site reactions (12% vs. 4%), accidental overdose (7% vs. 3%), and COVID-19 infection (8% vs. 5%).

“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,” Casale added.

References

1. _{Press release: Dupixent late-breaking positive phase 3 data in chronic spontaneous urticaria to be presented at Acaai. Sanofi. October 24, 2024. Accessed November 4, 2024. https://www.sanofi.com/en/media-room/press-releases/2024/2024-10-24-12-00-00-2968628.}
2. _{Johal KJ, Saini SS. Current and emerging treatments for chronic spontaneous urticaria. Ann Allergy Asthma Immunol. 2020 Oct;125(4):380-387. doi: 10.1016/j.anai.2019.08.465. Epub 2019 Sep 5. PMID: 31494233; PMCID: PMC7056515.}
3. _{Le Floc'h A, Allinne J, Nagashima K, Scott G, Birchard D, Asrat S, Bai Y, Lim WK, Martin J, Huang T, Potocky TB, Kim JH, Rafique A, Papadopoulos NJ, Stahl N, Yancopoulos GD, Murphy AJ, Sleeman MA, Orengo JM. Dual blockade of IL-4 and IL-13 with dupilumab, an IL-4Rα antibody, is required to broadly inhibit type 2 inflammation. Allergy. 2020 May;75(5):1188-1204. doi: 10.1111/all.14151. Epub 2020 Jan 3. PMID: 31838750; PMCID: PMC7317958.}