Success in Eosinophil-Targeted Treatments for EoE Remains Limited

While biologics targeting eosinophils have demonstrated improvements in various eosinophilic disorders, success has lagged for eosinophilic esophagitis (EoE), explained researchers of a new review published in World Allergy Organization Journal.

The researchers compiled data from studies of lirentelimab, mepolizumab, reslizumab, and benralizumab, highlighting the difficulties in finding an effective approach with eosinophil-targeted treatments for the condition.

“[Eosinophilic disorders] have been historically treated with corticosteroids and immunosuppressants, which are often, but not always, effective at reducing eosinophil counts and associated eosinophilic inflammation. However, these medications have long-term side effects that often limit dosing and efficacy,” explained the researchers. Capitalizing on knowledge regarding eosinophil cell biology has led to a remarkable increase in the development of eosinophil-specific therapies.”

Treatments targeting eosinophils have been studied for 2 decades, with various agents approved for eosinophilic disorders, including those targeting interleukin (IL)-5 (mepolizumab and reslizumab) and those targeting IL-5R (benralizumab). Biologics under investigation also include those targeting siglec-8 (lirentelimab).

For example, preliminary results from an ongoing phase 3 trial of intravenous (IV) lirentelimab showed histologic improvement in patients receiving the treatment, but there were no significant symptom improvements among patients.

“EoE has traditionally been treated with a mixture of elimination diets, proton pump inhibitors, and corticosteroids (systemic and swallowed topical) with a goal of reducing both symptoms and eliminating esophageal eosinophilia,” wrote the researchers. “While biologics targeting eosinophils are a plausible method of treating EoE, clinical trials to date have been disappointing.”

In a trial of 59 children aged 2 to 17 years with peak esophageal eosinophil count > 20/high-power field (hpf) who were refractory to treatment, just 8.8% of patients met the primary endpoint of an esophageal eosinophil count of < 5/hpf after 3 months of treatment with mepolizumab.

Secondary outcomes of the study included changes in peak and mean esophageal eosinophil counts, with counts of < 20/hpf achieved in 31.6% and 89.5% of patients, respectively. Other secondary outcomes included improvement in histopathologic and endoscopic findings, and frequency and severity of symptoms. Patients reported reductions in pain, regurgitation, and vomiting, through there were wide confidence internals. There was 1 reported adverse event related to treatment—chest pain—and no hypersensitivity reactions. The researchers noted that there is currently an additional phase 3 trial ongoing.

The safety and efficacy of reslizumab was assessed in a multicenter trial of over 200 patients aged 5 to 18 years who had moderate to severe disease with a peak esophageal eosinophil count > 24/hpf. Patients experienced a significant reduction in the peak esophageal eosinophil count—the study’s coprimary endpoint—across all doses—1, 2, or 3 mg/kg IV—with reductions ranging from 40%-50% compared with 5% among patients receiving placebo. However, no group of reslizumab-treated patients was able to achieve a peak esophageal eosinophil count of <5/hpf. There was also no significant improvement in physician’s EoE global assessment, the study’s second coprimary endpoint.

No significant changes were observed across secondary endpoints of the trial—patient predominant symptoms and children’s health questionnaire scores. Data from a 9-year open-label extension of the study showed no serious adverse events associated with reslizumab.

There is currently an ongoing phase 3 trial assessing the efficacy of subcutaneous benralizumab.

Reference

Pitlick MM, Li JT, Pongdee T. Current and emerging biologic therapies targeting eosinophilic disorders. World Allergy Organ J. 2022;15(8):100676. doi:10.1016/j.waojou.2022.100676