SAN DIEGO – An investigational human monoclonal antibody suggested a new approach to asthma treatment by showing evidence of anti-inflammatory activity and partial attenuation of early and late asthmatic responses in a proof-of-concept study of 31 patients with mild asthma.
Patients were randomized to intravenous treatment with AMG 157 or placebo for up to 3 months before undergoing allergen-induced challenge and testing. AMG 157 binds human thymic stromal lymphopoietin (TSLP), an epithelial-cell–derived cytokine that might be important in initiating allergic inflammation, and prevents receptor interaction.
Dr. Gail M. Gauvreau
By day 84, the maximum percentage decrease in the forced expiratory volume at 1 second (FEV1) during late asthmatic response (3-7 hours after allergy challenge) was 46% smaller in the treatment group, compared with placebo, a significant difference, Gail M. Gauvreau, Ph.D., and her associates reported at an international conference of the American Thoracic Society.
Among secondary outcomes, the area under the curve (AUC) of the time-adjusted percent decrease in FEV1 during the early asthmatic response was significantly smaller in the treatment group than the control group on day 84. Patients who got AMG 157 showed significantly lower levels of blood and sputum eosinophils before and after allergy challenge and in the fraction of exhaled nitric oxide.
Adverse events were reported in 15 patients on AMG 157 and 12 patients on placebo. No serious adverse events were seen, reported Dr. Gauvreau of the Firestone Institute of Respiratory Health at McMaster University, Hamilton, Ontario.
The study was published online by the New England Journal of Medicine (2014 May 20 [doi:10.1056/NEJMoa1402895]). "This proof-of-concept study suggests that TSLP is a pivotal cytokine not only in allergen-induced airway responses but also in persistent airway inflammation in patients with allergic asthma," the investigators wrote.
The company that is developing AMG 157 has started a phase II clinical trial, Dr. Gauvreau said in an interview at the meeting.
The population of mild asthmatics in the proof-of-concept study are not the kind of patients who might use this treatment, she said, but this potential treatment pathway offers hope for a new therapy for patients with steroid-resistant asthma. "They use an awful lot of resources and costs in terms of hospital emergency room care. They are the folks who have an unmet need to treat their asthma," she said.
Amgen, which is developing AMG 157, funded the study and analyzed the data. Dr. Gauvreau reported financial associations with Amgen and three other companies. Fourteen of her coinvestigators reported financial associations with Amgen and multiple other companies.