Promising results in AD treatment with an OX40 ligand inhibitor

Clinically meaningful improvements in Eczema Area and Severity Index (EASI) were observed with amlitelimab treatment for atopic dermatitis.

Study conducted on a typical moderate-to-severe AD population

STREAM-AD (NCT05131477) is a phase 2b monotherapy trial designed to test 5 different dosages of the OX40 ligand inhibitor amlitelimab against placebo in adults with moderate-to-severe AD, expressed by a baseline EASI of ≥16, an Investigator’s Global Assessment (IGA) of 3 or 4, and at least 10% of affected body surface area (BSA)1. Per design, 390 participants were randomised to a 4-weekly treatment with placebo or the study drug in 4 groups (250 mg + loading dose of 500 mg, 250 mg, 125 mg, or 62.5 mg). The primary endpoint was the proportion of EASI change at week 16. Follow-up of 6 more weeks completed part 1 of STREAM-AD.

“Overall, this was a typical moderate-to-severe AD population,” Prof. Stephan Weidinger (University Hospital Schleswig-Holstein, Germany) commented on the baseline characteristics. The mean age was 37.8 years, 43.8% were women, and the mean duration of AD was 22.3 years. Mean disease measures were EASI 28.9, IGA 3.3, and BSA involved 46.2%.

Following week 24 results, safety-follow up until week 68 is awaited

The study met its primary endpoint at week 16, with statistically significant superior EASI results that equalled least mean square changes between -61.5% (250 mg plus loading dose; P<0.0001) and -51.6% (125 mg; P=0.0002) compared with 29.4% in the placebo arm. On the highest dose, for example, EASI reductions continued up to week 24 with -64.4% or -73.1%, depending on the statistical approach to categorising cases of rescue medication.

Among the secondary endpoints were achievement of IGA 0/1, EASI75, and ≥4-point reduction on the Peak Pruritus Numerical Rating Scale (PP-NRS). Apart from IGA 0/1 on 250 mg without a loading dose, all groups on amlitelimab were significantly superior over placebo in these as well.

Up to week 24, treatment-emergent adverse events occurred in 67.4% (amlitelimab) and 60.3% (placebo) of the participants, with rates of treatment discontinuation at 4.5% and 6.4%, respectively. Overall, the agent was deemed well-tolerated.

The results of the second part of STREAM-AD, which includes a withdrawal/extension design for the 24-week responders and a safety follow-up until week 68, are eagerly awaited.

We invite you to visit our special site covering the EADV Congress 2023.

Source
  1. Weidinger S. Efficacy and safety of amlitelimab (an anti-OX40 ligand antibody) in patients with moderate-to-severe atopic dermatitis: 24-week results from a Phase 2b trial (STREAM-AD). D3T01.3G, EADV Congress 2023, 11–14 October, Berlin, Germany.