In the opinion of David Rosmarin, MD, the approval of dupilumab in 2017 for the treatment of moderate to severe, resistant atopic dermatitis (AD) marked an inflection point in dermatology.
“Dupilumab has revolutionized AD, and the [interleukin] IL-4 receptor target isn’t going away,” Dr. Rosmarin, who chairs the department of dermatology at Indiana University, said at the Revolutionizing Atopic Dermatitis (RAD) Virtual Conference. “It’s truly an exciting time because we have a lot of different treatments in the pipeline that target IL-4 and other receptors.”
CM310 (Stapokibart): This IL-4 receptor alpha monoclonal antibody, which is being developed by Keymed Biosciences, inhibits IL-4 and IL-13 signaling. In a phase 3 randomized study of patients with moderate to severe AD, presented as an abstract at the 2023 European Academy of Dermatology and Venereology (EADV) meeting, it showed results similar to those of dupilumab. Specifically, at week 16, Eczema Area and Severity Index (EASI)-75 scores were achieved in 66.9% of patients in the CM310 group and 25.8% of patients in the placebo group, while the proportion of patients achieving an Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with a reduction of greater than or equal to 2 points from baseline was 44.2% in the CM310 group, compared with 16.1% in the placebo group (P < .0001 for both associations). According to Dr. Rosmarin, other novel anti-IL-4 receptor antibodies for AD include AK120, which is being developed by Akeso Biopharma, and CBP-201 (rademikibart), which is being developed by Connect Biopharma.
Eblasakimab. Under development by ASLAN Pharmaceuticals, this biologic is a potential first-in-class, monoclonal antibody that binds to IL-13Ralpha1 with high affinity and blocks the signaling of IL-4 and IL-13 through the type-2 receptor. In the TREK-AD monotherapy phase 2b trial in patients with moderate to severe AD, presented as an abstract at the 2023 EADV meeting, the primary endpoint of EASI percent change from baseline to week 16, was met for eblasakimab doses 600 mg Q4W, 300mg Q2W, and 400mg Q2W vs. placebo (73.0% [P = .001], 69.8% [P = .005], and 65.8% [P = .029] vs. 51.1%), respectively.
Nemolizumab. Under development by Galderma, nemolizumab is a first-in-class IL-31 receptor alpha antagonist. “Many people refer to IL-31 as the itch cytokine,” Dr. Rosmarin said. “That’s probably a little oversimplified, but it’s certainly a powerful medication in development for prurigo nodularis as well as AD.”
Dr. Rosmarin
Dr. David Rosmarin
Results from the ARCADIA 1 and 2 trials, which included the concurrent use of topical corticosteroids and calcineurin inhibitors and were presented as an abstract at the 2023 EADV meeting, showed that nemolizumab significantly improved skin lesions and itch in adolescent and adult patients with moderate to severe atopic dermatitis, compared with placebo. Specifically, 35.6% and 37.7% of nemolizumab-treated patients in ARCADIA 1 and 2, respectively, reached clearance or almost-clearance of skin lesions when assessed using the IGA score, compared with 24.6% and 26.0% in the placebo group (P < .0006, P = .001). In addition, 43.5% and 42.1% of nemolizumab-treated patients in ARCADIA 1 and 2, respectively, achieved a 75% reduction in the EASI, compared with 29.0% and 30.2% in the placebo group (P < .0001, P = .0011). “There are similar results regardless of the degree of itch patients are starting out with at baseline,” Dr. Rosmarin said. “It’s a very rapid response, by week 4, and that continues to improve through week 16.”
Amlitelimab. Under development by Sanofi, this monoclonal antibody binds to OX40-Ligand, and is designed for patients with moderate to severe AD. According to results of a phase 2b trial that were presented in an abstract at the 2023 EADV meeting, patients treated with amlitelimab 250 mg Q4W with a 500 mg loading dose showed a 61.5% improvement in the average EASI score from baseline at week 16, compared with 29.4% of those who received placebo (P <.0001), with continued improvement seen through 24 weeks. “There are really strong results with EASI scores; clearly this medicine works compared to the placebo,” Dr. Rosmarin said. “It’s also improving other biomarkers as well, including eosinophils, IL-13, TARC [serum thymus and activation-regulated chemokine], and IL-22.”
138559 (Temtokibart). Under development by LEO, 138559 is the first biologic to show the efficacy and safety of an IL-22RA1 targeting antibody for the treatment of moderate-to-severe AD. In a phase 2a study abstract presented at the 2023 EADV meeting, the mean change in EASI from baseline to Week 16 was significantly greater for patients in the 138559-treated group compared with those in the placebo group (–15.3 vs. –3.5; P = .003). In addition, at week 16, significantly greater proportions of patients in the 138559 group relative to those in the placebo group achieved an EASI75 score (41.6% vs. 13.7%; P = .011) and an EASI-90 score (30.8% vs. 3.5%; P = .003). “With this particular receptor you’re not only blocking IL-22, but you’re blocking IL-20 and IL-24 as well,” Dr. Rosmarin said. “It really may be that it’s IL-20 and IL-24 that are more responsible for the pathogenic effect.”
Dr. Rosmarin disclosed that he is speaker for and/or a consultant and advisory board member to many pharmaceutical companies, including Galderma and Sanofi.