OX40: A novel treatment target in atopic dermatitis

In a phase 2a atopic dermatitis study, maintenance of response continued for months after last dose; this may hint at an option for extended medication intervals.

The 88 treated adult AD patients were all withdrawn from their topical medication

Amlitelimab is a non-depleting, anti-OX40 ligand antibody currently investigated for the treatment of moderate-to-severe AD. A phase 2a, randomised, controlled, parallel-group trial (NCT03754309) defined the incidence of treatment-emergent adverse events (TEAE) and efficacy in the EASI score at week 16 as co-primary endpoints¹. 

The 88 treated adult AD patients were all withdrawn from their topical medication, including corticosteroids, 14 days before baseline.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 those patients who achieved an Investigator’s Global Assessment (IGA) of 0/1 at week 16, in addition to safety, efficacy measures were taken to investigate the durability of response,” Prof. Stephan Weidinger (University of Kiel, Germany) pointed out.

The mean age of the study cohort was 33.6 years and 42% were women. The mean proportion of affected body surface area was around 50% and the mean EASI score was 30. The safety endpoint was met, as the rate of TEAE was determined non-different between active arms and placebo. “When adverse events 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.

The novel non-depleting amlitelimab demonstrated robust efficacy

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 further on. “Even with rather strong placebo responses, both doses were statistically significantly superior over placebo at week 12, when the first dose was applied, and amlitelimab low dose also demonstrated superiority at week 16, so 4 weeks after the last dose,” Prof Weidinger stressed. The proportion 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 the high as well as the low dose of amlitelimab compared with placebo at days 57, 85, and 113 (P<0.001 for all time-points). “Very 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 to 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 profile. A phase 2b study will start soon.