Long-term disease control in AD could be in reach with anti-OX40 antibody KHK4083

KHK4083 demonstrated great potential for the treatment of atopic dermatitis (AD). It not only induced significant reductions in Eczema Area and Severity Index (EASI) scores but also showed considerable maintenance of efficacy over 20 weeks in a recent phase 2 trial.

“Activation of Th2 and other T-cell subsets is central in AD and the OX40-OX40 ligand axis plays a critical role in long-lasting T-cell responses,” explained Prof. Emma Guttman-Yassky (Icahn School of Medicine at Mount Sinai, NY, USA) [1]. A multicentre, randomised-controlled, phase 2 study (NCT03703102) was designed to evaluate the efficacy and safety of different doses of the anti-OX40 monoclonal antibody KHK4083 in adult patients with moderate-to-severe AD. Enrolled 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 was 300 mg or 600 mg subcutaneously administered every 2 weeks or 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.

“KHK4083 was significantly superior to placebo in all groups, and the primary endpoint was met,” announced Prof. Guttman-Yassky. Reductions ranged from 48.3% (150 mg every 4 weeks) to 61.1% (300 mg every 2 weeks). In contrast, in the placebo group, the EASI score was reduced by 15.0%. EASI 75 responses rates at week 16 varied from 38.9% to 53.8% versus 15.01% under 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. Also at week 16, 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 (see Figure). “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 mg and 300 mg every 2 weeks) around 90% of patients maintained EASI 75 for 20 weeks after discontinuation of the study drug.

Figure: Proportions of patients who achieved an IGA score of 0/1 and a reduction of ≥2 points from baseline [1]
IGA, Investigator’s Global Assessment; Q2W, every 2 weeks; Q4W, every 4 weeks. Date based on non-responder imputations.

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.

Prof. Guttman-Yassky concluded that “KHK4083 may thus be a novel treatment option for patients with AD that need long-term disease control.”

1. 
   
   1. Guttman-Yassky E. Efficacy and safety results of KHK4083/AMG 451 (anti-OX40 mAb) in subjects with moderate to severe atopic dermatitis: a phase 2, multicentre, randomized, double-blind, parallel-group, placebo-controlled study. D3T01.1B, EADV Congress 2021, 29 Sept–2 Oct.

 

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Posted on 18 November 202119 November 2021