Biologics for Chronic Obstructive Pulmonary Disease: Present and Future

Abstract

An unmet need exists for effective treatments for patients with chronic obstructive pulmonary disease (COPD) who continue to experience exacerbations despite receiving standard-of-care treatments. Current advances for COPD are based on an evolving understanding of the molecular mechanisms of increased airway inflammation in stable-state COPD and during acute exacerbations. This review examines the current understanding of the underlying pathophysiology of COPD, discusses clinical trials of novel biologic treatments for COPD, and provides an overview of potential new targets for development of innovative therapies and biomarkers that may be used to identify appropriate patients for these novel treatments. The most promising biologic treatments at an advanced stage of development for COPD are agents targeting eosinophilia, either indirectly through anti-interleukin-5 (IL-5) or directly though anti-IL-5Rα (IL-5 receptor alpha) mechanisms. Targeting proteins involved in response to viral infection, such as IL-33, offers further potential for future advances in the development of biologics for COPD.

Benralizumab for the Prevention of COPD Exacerbations

“…COPD is a complex condition driven by a diverse range of mechanisms, which leads to a wide spectrum of clinical presentations. 20 Biologic agents such as benralizumab target a discrete potential pathologic mechanism (eosinophilic inflammation). By week 4, and through to week 56, benralizumab resulted in substantial depletion of blood eosinophils, and substantial depletion of sputum eosinophils had occurred by week 24.…”

Goals of COPD treatment: Focus on symptoms and exacerbations

“…Many novel treatments have failed to prevent exacerbations. This may be due to the use of inappropriate or ineffective molecules, or because the concept of a single medicine treating a heterogeneous disease such as COPD is unrealistic [65]. However, personalized medicine may have a role in preventing exacerbations in some COPD patients [9,11,[66][67][68].…”

Blood Eosinophil Counts in Clinical Trials for Chronic Obstructive Pulmonary Disease

“…Chronic obstructive pulmonary disease (COPD) is a complex condition with pathophysiology and clinical characteristics that vary in presence and severity between patients ( 1 ). This variability contributes to the range of treatment responses observed for patients with COPD for both established and experimental therapeutic interventions.…”