NEJM Publishes Positive Proof-of-Concept Data for New Asthma Treatment

Amgen has announced that The New England Journal of Medicine (NEJM) has published positive results from a Phase 1 study adding to the growing body of evidence that inhibiting thymic stromal lymphopoietin (TSLP) could be beneficial in the treatment of asthma.

TSLP is a cytokine thought to be a key driver of allergic inflammation. These are the first clinical data to be reported for an anti-TSLP therapy. The results were also presented at the American Thoracic Society 2014 international conference taking place in San Diego.

Results from the 31-patient study showed treatment for 12 weeks with AMG 157, a monoclonal antibody that inhibits the activity of TSLP, resulted in statistically significant reductions in early asthmatic responses (EAR) and late asthmatic responses (LAR) in the airways following allergen challenges in patients with allergic (atopic) asthma.

The data also showed statistically significant decreases in baseline markers of inflammation in the airways. Overall, adverse events were similar across treatment and placebo groups (15 events in the treatment arm versus 12 events in the placebo arm), with no serious adverse events occurring in the study.

"While these data are very early, they help to confirm our belief that TSLP is a critical early mediator that may be responsible for persisting airway inflammation and triggering the inflammatory response to allergens in allergic asthmatic patients," said Paul M. O'Byrne, MB, FRCPC, FRSC, executive director of the Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, Ontario, Canada. "These results form the basis for further development of this compound."

AMG 157 is a monoclonal immunoglobulin IgG2λ that binds to and inhibits TSLP from interacting with its receptor. TSLP is a cytokine that is believed to play a critical role in the start of the allergic cascade, specifically the inflammatory response, and is generated by lung tissue when an allergen is introduced.

Studies have also shown higher amounts of TSLP were produced in the lung tissue of individuals with asthma compared to healthy individuals, and the TSLP gene has been associated with both childhood and adult allergic asthma.

"Understanding the underlying biology of disease is critically important to continuing to discover novel treatments for patients suffering from a variety of diseases," said Brian Kotzin, M.D., vice president of Global Development at Amgen. "These data give us insight into the importance of TSLP as a mediator of asthmatic response and the ability to inhibit inflammation in asthma."

MEDI9929/AMG 157 is being jointly developed by Amgen and AstraZeneca, with its global biologics research and development arm MedImmune. MEDI9929/AMG 157 is currently in Phase 2 development for the treatment of asthma.

"We are encouraged by these early results and look forward to leading further development of this promising new biologic in partnership with Amgen," said Bing Yao, Ph.D., senior vice president and head of MedImmune's Respiratory, Inflammation and Autoimmunity Innovative Medicines Unit. "The goal of the Phase 2 study is to understand if this approach could provide benefit for patients with severe asthma."

Study Design

The double-blind, placebo-controlled parallel-group study was conducted as a proof-of-concept study to determine whether treatment with AMG 157 prevents allergen-induced airway responses in patients with allergic asthma.

Thirty-one participants who developed EAR and LAR were enrolled and randomized to AMG 157 (n=16) or placebo (n=15). Participants received three doses of AMG 157 (700 mg intravenously) or placebo, four weeks apart. Allergen challenges were conducted on days -14, 42 and 84.