The late-breaking, multicentre, randomised-controlled, phase 2 study (NCT03703102) was designed to evaluate the anti-OX40 monoclonal antibody KHK4083 for moderate-to-severe atopic dermatitis (AD)1. Included were 273 patients, all presenting with EASI ≥16, Investigator’s Global Assessment (IGA) ≥3, involved body surface area ≥10%, and prior failure of topical medications. The mean age of the participants was 38 years and 41.4% were women.
The dosing of KHK4083 in the 4 primary active study drug arms were: subcutaneously administered 300 mg or 600 mg every second week, as well as 150 mg or 600 mg every 4 weeks. The first phase of the study continued up to week 18 with the last drug administration at week 16. Thereafter, patients in the placebo group were switched to 600 mg KHK4083 every 2 weeks for the second half of the study until week 36. Further follow-up was performed every 4 weeks until week 56.
The primary endpoint consisted of the change in EASI at week 16. Reaching EASI 50, 75, 90, and IGA 0/1 were among the secondary endpoints. The participants’ baseline parameters were evenly distributed among the 4 primary active study drug arms, but the proportion of men was around 10% higher in the 150 mg arm than in the other arms.
“All the groups treated with the drug achieved the primary endpoint significantly as compared with placebo, with 2 stars of significance and a P-value of <0.001,” announced Prof. Emma Guttman-Yassky (Icahn School of Medicine at Mount Sinai, NY, USA). Reductions ranged from 48.33% (150 mg every 4 weeks) to 61.07% (300 mg every 2 weeks). Whereas in placebo group, EASI score was reduced by 15.01%. EASI 75 responses rates at week 16 varied from 38.9% to 53.8% (P<0.001 for all comparisons vs placebo).
These values continued to improve until week 36 with EASI 75 in 51.9% to 63.5% of patients on KHK4083 from the start and 35.1% in the former placebo group after switching. At the same time-point, 53.8% in the 300 mg every 2 weeks arm achieved EASI 90.
Similar trends were seen for IGA 0/1 with a ≥2-point reduction from baseline and also a ≥4-point reduction on the pruritus numerical rating scale. “An important feature and maybe a unique feature of this drug is the durability of response,” Prof. Guttman-Yassky emphasised, highlighting that in both high-dose arms (i.e. 600 and 300 mg every 2 weeks) around 90% of patients maintained EASI 75 for 20 weeks after discontinuation of the study drug.
Treatment-emergent adverse events were experienced by 81% of the participants on an active drug regimen and 71.9% on placebo. The most common events were pyrexia, nasopharyngitis, worsening of AD, and chills. The severity of pyrexia and chills was mostly mild to moderate. No hypersensitivity reactions or deaths were reported.
“KHK4083 may thus be a novel treatment option for patients with AD that need long-term disease control,” Prof. Guttman-Yassky concluded.