Cendakimab effective, safe, and well-tolerated in patients with moderate to severe atopic dermatitis: JAMA

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by severe itching, redness, and a range of other symptoms that can significantly impact a patient’s quality of life. IL-13 is considered a key type 2 cytokine in the development of AD and would thus be a prime target for therapeutic intervention. Cendakimab is a selective inhibitor of IL-13, interacting with its receptors IL13R-α1 and IL13R-α2. Targeting of IL-13 has been shown earlier to reduce the inflammation and improve the skin condition in AD, thus providing the rationale for the use of cendakimab.

This was a randomized, double-blind, placebo-controlled phase 2 clinical trial conducted from May 2021 to November 2022 in 69 sites across the United States, Japan, Canada, Poland, and the Czech Republic, with 221 adult patients having moderate to severe AD and who had an inadequate response to topical medications. Participants were randomized to 360 mg cendakimab every two weeks, 720 mg every two weeks, 720 mg once a week, or matching placebo.

The primary endpoint measure was the mean percentage change in EASI score from baseline to week 16. In this hierarchical testing, using a multiple comparison method of the different dosing regimens of cendakimab, the comparison with placebo was performed in sequential order to show its efficacy.

Key Findings

• The study found that patients receiving 720 mg of cendakimab once weekly experienced a significant reduction in EASI scores compared to those receiving a placebo (–84.4% vs –62.7%; P = .003), meeting the primary endpoint of the trial.

• While the 720 mg dose administered every two weeks showed a reduction in EASI scores (–76.0%), it did not reach statistical significance compared to the placebo (P = .06).

• The 360 mg dose every two weeks resulted in a similar reduction in EASI scores (−16.3%) to the 720 mg once-weekly dose (−21.8%); however, statistical significance could not be claimed due to the interruption in the hierarchical testing sequence.

• Treatment-emergent adverse events leading to discontinuation were observed in a small proportion of patients across all treatment groups: 4 patients (7.4%) in the 720 mg once-weekly group, 2 patients (3.6%) in the 720 mg every two weeks group, 1 patient (1.8%) in the 360 mg every two weeks group, and 2 patients (3.6%) in the placebo group. These results indicate that cendakimab was generally safe and well-tolerated.

These results indicate that cendakimab is a very useful treatment for AD of moderate to severe intensity at a dosage of 720 mg administered once a week. Indeed, the important decline in EASI scores with this dosing regime indicated that patients with AD can experience cendakimab-induced, clinically important improvements, particularly in those who have not responded adequately to other treatments.

The overall safety profile of cendakimab was favorable, and the rate of AEs leading to withdrawal was low. This is a very promising safety and efficacy profile for cendakimab as a therapy in AD and probably opens up an excellent new route of treatment in the management of this chronic, often debilitating, condition.

In summary, this study proved the efficacy and general safety of cendakimab in the treatment of moderate to severe atopic dermatitis, with the highest dosing frequency of 720 mg once a week showing the greatest improvements. These findings point to cendakimab as a potential valuable addition to the therapeutic arsenal for AD, particularly in those patients who have otherwise failed conventional topical therapies.

Reference:

Blauvelt, A., Guttman-Yassky, E., Lynde, C., Khattri, S., Schlessinger, J., Imafuku, S., Tada, Y., Morita, A., Wiseman, M., Kwiek, B., Machkova, M., Zhang, P., Linaberry, M., Li, J., Zhang, S., Franchin, G., Charles, E. D., De Oliveira, C. H. M. C., & Silverberg, J. I. (2024). Cendakimab in patients with moderate to severe atopic dermatitis: A randomized clinical trial. JAMA Dermatology (Chicago, Ill.). https://doi.org/10.1001/jamadermatol.2024.2131