The inflammation results from a dysregulated immune response and the lesions that form are characterised by erythema and itching. In severe cases, skin can become thick and leathery.
Papules may occur and there may be oozing and crusting on the surface. Up to one in 10 adults are affected, about a third of whom have moderate to severe symptoms.
Treatment historically relied on topical steroids; and, although alternative drug therapies have been introduced in recent years, more effective options are still very much needed.
One such drug, eblasakimab, is being developed by Aslan Pharmaceuticals. The monoclonal antibody targets the IL-13 receptor subunit of the Type 2 receptor complex, a key pathway that drives a number of allergic inflammatory diseases.
By blocking the Type 2 receptor, it prevents signalling through both IL-4 and IL-13, the key drivers of inflammation in atopic dermatitis.
In a Phase Ia open label study, single ascending doses were administered via intravenous or subcutaneous injection to healthy male volunteers.1
Its effect on IL-13 receptor occupancy and STAT6 phosphorylation was assessed in blood monocytes. No serious treatment-emergent adverse events were observed. Single doses of 3 mg/kg given intravenously, and 300 mg subcutaneously, both effectively blocked the receptor and inhibited STAT6 phosphorylation.
The results supported further development with 2- or 4-weekly dosing.
The company has also announced top line data from a Phase IIb dose ranging study of the antibody in adult patients with moderate to severe disease.
In the study, 289 patients were randomised across five dosing arms; they were given 300 or 400 mg doses every 2 weeks, 400 or 600 mg doses every 4 weeks or a placebo for 16 weeks.
Patients on both the 2-weekly regimens and the higher 4-weekly dose had a rapid onset of action in the first few weeks of treatment, with a statistically significant improvement in eczema area and severity index (EASI) scores by week 4.
Discontinuation rates were comparable between the active treatment arms (and higher among patients given the placebo).
The frequency of adverse events was comparable across all groups, with the most commonly observed being nasopharyngitis, atopic dermatitis, headache and upper respiratory tract infection.
The company expects further data to be available later in the year, including patient-reported outcomes and biomarker data.
It hopes to start Phase III evaluation in 2024. A study is also under way looking at its effectiveness in patients who have previously been treated with dupilumab, with top line data from that study expected in early 2024.
Reference
- F. Cevikbas, et al., Clin. Immunol. 253, 109677 (2023).