Abstract

The development of novel therapies for COPD requires a precision medicine approach, using both clinical information (clinical phenotype) and biological markers (endotypes) in order to identify sub-groups with the greatest potential for therapeutic benefit. Drugs with novel mechanisms of action are being developed for COPD. Early phase clinical trials using experimental medicine approaches can identify which drugs are more likely to have clinical efficacy. This presentation will cover the most promising new drug classes in COPD, focusing on experimental medicine studies and the identification of responder subgroups. The airway epithelium senses external danger signals to initiate host innate immune defence mechanisms by the rapid secretion of alarmins including thymic stromal lymphopoieten (TSLP) and interleukin (IL-33). These alarmins are capable of initiating both type-2 (T2) and non-T2 immune responses. Biological treatments targeting the IL-33 pathway have shown clinical efficacy in phase 2 COPD studies. Interestingly, the efficacy of itepekimab (which targets IL-33) on exacerbation rate reduction in COPD patients appeared to be greater in ex-smokers compared to current smokers. This finding, if confirmed, may lead to biological treatment in COPD that is confined to ex-smokers. Ensifentrine is an inhibitor of both the phosphodiesterase (PDE)3 and PDE4 isoforms. PDE3 controls smooth muscle tone; PDE3 inhibition causes bronchodilation and also has some anti-inflammatory effects. PDE4 inhibition has the potential to exert broad anti-inflammatory effects. Ensifentrine has demonstrated bronchodilation and symptom improvement in COPD clinical trials, and has the possibility to be the first novel bronchodilator to be successfully developed for decades.