Cendakimab Shows Efficacy and Safety in Treating Moderate to Severe Atopic Dermatitis: Results from Clinical Trial

The findings, published in JAMA Dermatology, demonstrated improvements in pruritus, skin clearance, and the extent and severity of AD compared with placebo. Cendakimab was generally safe and well-tolerated.

Cendakimab selectively targets interleukin (IL)-13, a type 2 cytokine involved in the pathogenesis of atopic dermatitis (AD), by blocking its binding to IL13R-α1 and IL13R-α2 receptors. Proof-of-concept studies in AD endorse cendakimab as a potential treatment for type 2 inflammatory diseases. Considering this, Andrew Blauvelt, Oregon Medical Research Center, Portland, Oregon, and colleagues aimed to evaluate the safety and efficacy of cendakimab compared with placebo in patients with moderate to severe AD.

For this purpose, the researchers conducted a phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging clinical trial from 2021 to 2021. It enrolled adult patients with moderate to severe AD and inadequate response to topical medications at 69 sites in 5 countries (Japan [n = 17], US [n = 26], Czech Republic [n = 8], Poland [n = 9], and Canada [n = 9]).

Patients were randomized in a 1:1:1:1 ratio to receive subcutaneous cendakimab, 360 mg, every two weeks; 720 mg, every two weeks; 720 mg, once weekly; or placebo.

The study evaluated the mean percentage change in Eczema Area and Severity Index (EASI) scores from baseline to week 16. Hierarchical testing with adjustment for multiple comparisons was conducted for the following comparisons: 720 mg once weekly versus placebo, followed by 720 mg every two weeks vs placebo, and finally, 360 mg every two weeks vs placebo.

The study led to the following findings:

• Two-hundred twenty-one patients were randomized, and 220 received the study drug (43% women; mean age, 37.7 years; 720 mg, once weekly [24%]; 720 mg, every two weeks [25%]; 360 mg, every two weeks [25%]; placebo [26%]).
• The primary efficacy endpoint was met for cendakimab, 720 mg, once weekly versus placebo (–84.4 versus –62.7) but missed statistical significance for 720 mg, every two weeks (–76.0 versus –62.7).
• The treatment effect for 360 mg every two weeks (−16.3 versus placebo) was comparable with 720 mg once weekly (−21.8); however, significance was not claimed because the hierarchical testing sequence was interrupted.
• Of patients with treatment-emergent adverse events leading to discontinuation, 7.4% received 720 mg once weekly; 3.6% 720 mg every two weeks; 1.8% 360 mg every two weeks; and 3.6% placebo.

"In the randomized clinical trial, cendakimab proved effective, safe, and well-tolerated for patients with moderate to severe atopic dermatitis (AD). The primary endpoint, a significant reduction in Eczema Area and Severity Index (EASI) scores at week 16, was achieved with the 720 mg once-weekly dose. Across all doses, cendakimab showed continuous improvement in AD over the 16-week treatment period," the researchers concluded.

Reference:

Blauvelt A, Guttman-Yassky E, Lynde C, et al. Cendakimab in Patients With Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol. Published online July 17, 2024. doi:10.1001/jamadermatol.2024.2131