Ecleralimab administration is a safe intervention in patients suffering from mild atopic asthma, as it is effective in attenuating airway inflammation and allergen-induced bronchoconstriction.
Thymic stromal lymphopoietin (TSLP) is an upstream regulator that mediates inflammatory responses, including type 2 inflammation in asthma. Ecleralimab is a neutralizing antibody fragment that works against human TSLP, and was developed for inhalation administration. This randomized controlled trial investigated the safety and efficacy of ecleralimab against human TSLP by utilizing the allergen inhalation challenge (AIC) in mild atopic asthma patients. The study findings, published in the European Respiratory Journal, indicate that this neutralizing antibody fragment is both safe and effective in attenuating allergen-induced airway inflammation and bronchoconstriction.
Baseline Characteristics of Mild Atopic Asthma Patients
Of a total of 28 patients with mild atopic asthma enrolled in the trial, 13 received a placebo and 15 received ecleralimab. At the screening of the allergen challenge, both the late asthmatic response (LAR) and the early asthmatic response (EAR) were similar in the placebo and ecleralimab groups.
Early and Late Asthmatic Responses in Study Subjects
Ecleralimab significantly improved LAR, as recorded on day 84 of treatment, with LAR being 11.38% and 4.2% in the placebo and ecleralimab groups, respectively. Ecleralimab significantly attenuated the LAR%, with a 48% reduction in the treatment group compared to the placebo group. There were no statistically significant differences in the EAR of atopic asthma patients who were treated with ecleralimab compared to placebo as measured at days 42 and 84.
Allergen-Induced Inflammation of the Airway
Compared to the placebo group, there was a significant attenuation of allergen-induced sputum eosinophils with the administration of ecleralimab. However, ecleralimab did not influence pre-allergen sputum eosinophil levels measured on days 41 or 83. Compared to the placebo group, the ecleralimab group demonstrated a significant improvement in the baseline fractional exhaled nitric oxide (FENO) by day 17. There was a significant reduction in FENO associated with ecleralimab administration throughout the treatment period of 12 weeks, except for days 43 and 85.
Ecleralimab and Airway Hyperresponsiveness
According to the current study, there were no differences in the blood eosinophil levels in the placebo and ecleralimab group patients. While ecleralimab mediated an increase in methacholine PC20 at days 41 and 83, the neutralizing antibody fragment did not have any effects on methacholine PC20 at days 43 and 85.
Safety Profile of Ecleralimab
A total of 93 treatment-emergent adverse events were reported by 22 study subjects, of which 51 were reported by 10 patients in the ecleralimab group and 42 were reported by 12 patients in the placebo group. Most of the adverse events were mild, with the most frequent being oropharyngeal pain, headache, and nasopharyngitis.
Gauvreau, G. M., Hohlfeld, J. M., FitzGerald, J. M., Boulet, L. P., Cockcroft, D. W., Davis, B. E., Korn, S., Kornmann, O., Leigh, R., Mayers, I., Watz, H., Grant, S. S., Jain, M., Cabanski, M., Pertel, P. E., Jones, I., Lecot, J. R., Cao, H., & O’Byrne, P. M. (2023). Inhaled anti-TSLP antibody fragment, ecleralimab, blocks responses to allergen in mild asthma. European Respiratory Journal, 61(3). https://doi.org/10.1183/13993003.01193-2022