Therapeutic Targets and Precision Medicine in COPD: Inflammation, Ion Channels, Both, or Neither?

Abstract

The development of a wider range of therapeutic options is a key objective in drug discovery for chronic obstructive pulmonary disease (COPD). Fundamental advances in lung biology have the potential to greatly expand the number of therapeutic targets in COPD. The recently reported successful Phase 3 clinical trial of the first biologic agent for COPD, the monoclonal antibody dupilumab, adds additional support to the importance of targeting inflammatory pathways in COPD. However, numerous other cellular mechanisms are important targets in COPD therapeutics, including airway remodeling, the CFTR ion channel, and mucociliary function. Some of these emerging targets can be exploited by the expanded use of existing COPD drugs, such as roflumilast, while targeting others will require the development of novel molecular entities. The identification of additional therapeutic targets and agents has the potential to greatly expand the value of using clinical and biomarker data to classify COPD into specific subsets, each of which can be predictive of an enhanced response to specific subset(s) of targeted therapies. The author reviews established and emerging drug targets in COPD and uses this as a framework to define a novel classification of COPD based on therapeutic targets. This novel classification has the potential to enhance precision medicine in COPD patient care and to accelerate clinical trials and pre-clinical drug discovery efforts.

Identification of novel biomarkers related to neutrophilic inflammation in COPD

“…As demonstrated by numerous RCT trials (e.g., pivotal clinical trials of roflumilast and dupilumab, etc. ), identifying these targets can greatly elucidate therapeutic regimens for individual patients, thereby facilitating the development of precision medicine ( 24 ). Neutrophil inflammation plays a central role in the pathophysiology of COPD and persists in the entire disease process, but targets for its action remain relatively scarce, making the identification of new biomarkers of neutrophilic inflammation critical to developing effective therapeutic options for COPD.…”