Biopsies indicate that interleukin-13 is the primary cytokine responsible for the condition; as such, blocking IL-13 is a potential treatment option.
The monoclonal antibody lebrikizumab was designed to bind selectively to IL-13, preventing the formation of the heterodimer complex that leads to the signalling cascade that results in the problematic lesions and associated symptoms. It is being developed by Lilly and Almirall.
Its efficacy and safety were evaluated in a group of atopic dermatitis patients whose symptoms were not adequately controlled by corticosteroid treatment alone.1
In a randomised, placebo-controlled, double-blind Phase II study, 209 adult patients with moderate to severe atopic dermatitis all used topical corticosteroids twice a day; after 2 weeks, they were randomised to receive a single dose of 125 mg or 250 mg of lebrikizumab, or 125 mg or a placebo every 4 weeks for 12 weeks.
The primary endpoint was the percentage of patients who achieved a 50% reduction in the eczema area and severity index (EASI) at week 12. At that point, 82% of the 4-weekly dosing patients achieved EASI-50 compared with 62% with the placebo.
There were no statistically significant improvements compared with the placebo with either single dose regimen. The incidence of adverse events was similar for all groups and these were mostly moderate or mild.
It has also been studied as a single agent treatment. In a Phase II double-blind, placebo-controlled dose ranging randomised clinical trial, 280 patients with moderate to severe atopic dermatitis were given subcutaneous injections of a placebo every 2 weeks, or 125 mg of lebrikizumab every 4 weeks with a 250 mg loading dose, 250 mg every 4 weeks or 250 mg every 2 weeks with the first two doses at 500 mg.2
All groups given the antibody had dose-dependent and statistically significant improvements in the primary endpoint of an improvement in EASI at week 16. Improvements were seen as early as the second day of treatment.
Top line results of two placebo-controlled Phase III trials have been released via press release. In both of these, the antibody met all primary and key secondary endpoints, including itch improvement and skin clearance.
These two trials continue and three further Phase III studies are in progress. The antibody is also being evaluated for other indications.
These include idiopathic pulmonary fibrosis, in which a Phase II trial in combination with pirfenidone did not meet its primary endpoint.3 Multiple studies have also been conducted in asthma patients.
References
- E.L. Simpson, et al., J. Am. Acad. Dermatol. 78, 863 (2018).
- E. Guttman-Yassky, et al., JAMA Dermatol. 156, 411 (2020).
- T.M. Maher, et al., Eur. Respir. J. 57, 1902442 (2021).