Monoclonal Antibody May Improve EoE Complications

An anti-interleukin-13 (anti-IL-13) antibody—RPC4046—can reduce biomarkers that mediate fibrostenosis, the most serious complication of eosinophilic esophagitis (EoE), according to new research.

This finding arose after researchers examined whether RPC4046 could modulate biomarkers for epithelial-mesenchymal transition (EMT) in patients with EoE.

In a substudy of a phase 2, double-blind, placebo-controlled trial, 69 patients with EoE were randomly assigned to weekly doses of RPC4046, 180 mg (n = 19); RPC4046, 360 mg (n = 26); or placebo (n = 24).

Esophageal biopsies were performed at baseline and at week 16, which were then analyzed to assess changes in the percentage of vimentin-positive epithelial cells, total e-cadherin, and vimentin:e-cadherin ratio per cell.

Overall, the mean percentage of vimentin-positive cells decreased 2.75% in the 180 mg-dose group and 4.24% in the 360 mg-dose group, compared with a decrease of 0.94% in the placebo group. In both dose groups, the researchers found a 5.6-fold increase in e-cadherin expression per cell vs placebo. This finding correlated with improvements in histology, eosinophil counts, endoscopic findings, and symptoms among the participants with EoE who received RPC4046.

“RPC4046 significantly reduced EMT markers in adults with active EoE, with greater effects at 360 mg,” the researchers concluded. “Together with results for eosinophil density and clinical endpoints from the main trial, these data support the hypothesis that pharmacologic IL-13 inhibition ameliorates both inflammatory and remodeling pathways, and could potentially reduce the risk of fibrostenotic complications.”

—Rebecca Mashaw

Reference:

Gann P, Deaton RJ, McMahon N, et al. An anti-IL-13 antibody reverses epithelial-mesenchymal transition biomarkers in eosinophilic esophagitis: phase 2 trial results. Published online May 11, 2020. J Allergy Clin Immunol. https://doi.org/10.1016/j.jaci.2020.03.045