Comparison of topical Nomacopan, a dual Complement and leukotriene LTB4 inhibitor, with dexamethasone in downregulating experimental allergic conjunctival disease (EAC)

Abstract

Purpose : Allergic eye disease can lead to corneal cicatrisation and vision loss. Topical or systemic dexamethasone and/or cyclosporin A is often required. Topical administration of Nomacopan, a bifunctional recombinant biologic, was shown to effectively attenuate ocular surface inflammation in a model of experimental allergic conjunctival disease (EAC)¹. The aim of this study was to compare the anti-inflammatory effects of Nomacopan with topical dexamethasone.

Methods : EAC was induced by immunizing 8-10 week old female C57Bl/6J mice (n=8 per group) with ovalbumin (OVA; 1mg)² followed, on day 21, with once daily challenges with topical OVA (250ug/mL) for 12 days. Ocular surface inflammation was readily detectable by Day 5 of OVA challenge. Topical Nomacopan at various concentrations (0.063%-0.5%) or dexamethasone (0.1%) was applied twice daily in both eyes from Day 6. Placebo-treated and unchallenged groups were used as controls. All eyes were examined daily and clinical scores assessed from Day 7 post OVA challenge. Animals were euthanised and eyes harvested for histology, flow cytometry and intracellular cytokine expression.

Results : Nomacopan (0.25, 0.5%), but not dexamethasone, significantly downregulated EAC on Day 7 whereas, on Day 10, all three treatments were equally effective when compared to placebo in decreasing EAC clinical scores [p=0.001]. Lower concentrations of Nomacopan were ineffective. Histological findings matched the clinical scores. Conjunctival CD4⁺T cells were elevated in all treatment groups compared to unchallenged animals. Percentages of conjunctival IL-9⁺cells and IL-4⁺GATA3⁺ CD4⁺T cells (Th2) were increased in all OVA challenged groups and were significantly inhibited by Nomacopan treatment, but not by dexamethasone. In contrast, IL-4⁺IL-9⁺CD4⁺T cells were significantly decreased [P<0.001] by all three treatments.

Conclusions : Topical Nomacopan suppressed inflammation in EAC by downregulating Th2 and Th9 cells, whereas dexamethasone only decreased Th9 cells, suggesting Nomacopan as an additional treatment option for allergic eye disease.

¹Eskandarpour ME et al. Allergy. 2021 Oct 6. doi: 10.1111/all.15128
² Adahome Sd et al. JCI Insight. 2016 Aug 4;1(12):e87001

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.