S446 Results from KRYPTOS, a Phase 2/3 Study of Lirentelimab (AK002) in Adults and Adolescents With EoE

Abstract

Introduction: Up until a couple of decades ago, eosinophilic esophagitis in adults (EoE) was considered uncommon, but its incidence has increased dramatically in recent decades (de Rooj WE 2021). In this retrospective study, we compare the number of cases of EoE across various regions in the United states and aim to identify regional trends. Methods: We performed a retrospective cross-sectional study of adults presenting to the ED and/or admitted to the hospital with eosinophilic esophagitis from 2016 through 2021 at 185 HCA hospitals across the United States. A total of 5,283 unique patients were included in the study. The inclusion criteria were all patients ages 18 years and older with a diagnosis of eosinophilic esophagitis. Patients with visit problems suggestive of other known cause of dysphagia such esophageal cancer, candida esophagitis, immunocompromised, were excluded. Results: The mean age of patients was 46 years. 17.8% of EOE encounters involved food impaction, and 14.9% of patients had a diagnosis of asthma. Our data revealed a statistically significant difference in EoE encounters based on year. There was an increase in the percent of patients seen for EOE each year from 2016-2021 (p50.025). East North Central (ENC) region had the greatest number of EoE cases per 100,000 patients for each given year (Figure A). ENC, had a dramatic increase in encounters from 2016 (21.08/100,000 patients) to reaching its peak in 2017 (47.23/100,000 patients). The West South-Central region had the least amount of EoE encounters for each given year (Figure A). There was no statistically significant seasonal difference in encounter frequency (Figure B). Conclusion:The geographical data of EoE cases, reveal an overwhelming rate of EoE cases in the East North Central region of the United States. Our study demonstrated significant regional variations within the United States for hospitalizations and ED visits for EoE patients. Given the association of EoE and allergic diseases, further investigation could include comparing our findings with regional rates of encounters for asthma and allergies.

Mepolizumab for treatment of adolescents and adults with eosinophilic oesophagitis: a multicentre, randomised, double-blind, placebo-controlled clinical trial

“…Another possibility is that targeting the IL-5 pathway alone, while effective for decreasing eosinophil counts, may not be effective for fully controlling all aspects of EoE. Recent studies of more potent eosinophil depleting medications such as lirentelimab (anti-siglec-8) and benralizumab (anti-IL-5R) showed a marked histological response with no overall symptom benefit compared with placebo 48 49. This suggests that though eosinophils are a biomarker for diagnosis of EoE and key effector cells,1 2 they may not be solely responsible for driving EoE pathogenesis.…”

Review article: Emerging insights into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis and other eosinophilic gastrointestinal diseases

“…In phase 2/3 study of EoE, lirentelimab let to marked histologic improvement with decreased eosinophil counts compared to placebo, but symptoms of dysphagia did not improve compared to placebo. 149 Another phase 3 trial of an eosinophil-depleting agent, the IL-5RA antibody benralizumab, had similar results. It led to very high histologic response rates compared to placebo, but did not lead to symptomatic or endoscopic improvement compared to placebo, and non-eosinophil count histologic findings were also unchanged.…”

“…Another biologic tested in EoE was an antibody against the siglec‐8 receptor, which is primarily found on eosinophils and mast cells, as when activated by the medication called lirentelimab, leads to eosinophil depletion and mast cell inactivation. In phase 2/3 study of EoE, lirentelimab let to marked histologic improvement with decreased eosinophil counts compared to placebo, but symptoms of dysphagia did not improve compared to placebo 149 . Another phase 3 trial of an eosinophil‐depleting agent, the IL‐5RA antibody benralizumab, had similar results.…”

World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management

“…219,220,221 Although it led to significant reduction in tissue eosinophils, no significant improvement was noted in patient-reported outcomes in comparison to placebo in patients with those disorders. 222 Lirentelimab has not been studied in HES.…”

“…Lirentelimab (AK002), is humanized anti‐siglec‐8 monoclonal antibody that has been studied in eosinophilic gastritis and duodenitis. 219,220,221 Although it led to significant reduction in tissue eosinophils, no significant improvement was noted in patient‐reported outcomes in comparison to placebo in patients with those disorders 222 . Lirentelimab has not been studied in HES.…”