Targeting OX40 in the treatment of atopic dermatitis meets expectations

Amlitelimab, an agent in a novel drug class, has exhibited promise in the treatment of atopic dermatitis (AD). Not only were the co-primary endpoints of the phase 2a study met, but the lasting response maintenance after the last drug intake might indicate the possibility of extended dosing regimens.

A randomised, controlled, parallel-group, phase 2a trial (NCT03754309) investigated the non-depleting anti-OX40 ligand antibody amlitelimab for the treatment of moderate-to-severe AD [1]. “By blocking the interaction of antigen-presenting cells and T cells rather high up in the immune cascade, amlitelimab has the benefit of impacting not only type 2 pathways but also other immune axes, in particular Th17, Th22, and Th1 pathways, that have all been implicated in AD in particular in chronic-lesional stages,” Prof. Stephan Weidinger (University Hospital Schleswig-Holstein, Germany) explained the special features of the study drug. The current study defined the number of treatment-emergent adverse events (AE) and efficacy as determined by % change from baseline in the Eczema Area and Severity Index (EASI) score at week 16 as co-primary endpoints.

The 88 treated adult participants with AD were all withdrawn from their topical medication, including corticosteroids, 14 days before baseline. They were randomised to either amlitelimab high dose (i.e. 500 mg loading/250 mg every 4 weeks), low dose (i.e. 200 mg loading/100 mg every 4 weeks), or placebo. “In patients who achieved an Investigator’s Global Assessment (IGA) of 0/1 [representing clear or almost clear skin] at week 16, in addition to safety, efficacy measures were taken to investigate the durability of response,” Prof. Weidinger pointed out.

The mean proportion of affected body surface area was around 50% and the mean EASI score was about 30. The safety endpoint was met, as the rate of treatment-emergent AEs was similar between active arms and placebo. “When AEs are ranked in system organ class by frequency, it is not surprising to see infections as the most frequently reported events. There was no meaningful imbalance between amlitelimab and placebo, and the most commonly seen events were nasopharyngitis, folliculitis, and upper respiratory tract infections,” stated Prof. Weidinger.

Durable response for several months without treatment

As for efficacy in terms of percentage EASI change from baseline, the onset of action was apparent as early as day 15 and continued to increase. “Even with rather strong placebo responses, both doses were statistically significantly superior over placebo at week 12, when the last dose was applied, and amlitelimab low dose also demonstrated superiority at week 16, so 4 weeks after the last dose,” Prof. Weidinger stressed. The proportions of patients with a clinically meaningful ≥4-point itch reduction in the numeric rating scale were 57.9% (low dose) and 62.5% (high dose) compared with 38.1% in the placebo group. Furthermore, the results for achieving IGA 0/1 were significantly greater for both high-dose and low-dose amlitelimab compared with placebo at days 57, 85, and 113 (P<0.001 for all time points). “Interestingly, in around 70% of patients, this excellent response was maintained over time until day 253, so it was maintained for several months without treatment. This could indicate a long and sustained response following the last dose, opening up the opportunity of extended dosing,” Prof. Weidinger remarked.

He summarised that the novel, non-depleting, anti-OX40 ligand monoclonal antibody amlitelimab demonstrated robust efficacy in the treatment of moderate-to-severe AD with an acceptable and unremarkable safety profile. A phase 2b dose-ranging study is being planned.

1. 
   
   1. Weidinger S. A phase 2a study of KY1005, a novel non-depleting anti-OX40 ligand (OX40L) mAb in patients with moderate to severe AD. D1T01.3A, EADV Congress 2021, 29 Sept–2 Oct.

 

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Posted on 18 November 202118 November 2021