Review of Drug Development Guidance to Treat Chronic Obstructive Pulmonary Disease:USandEUPerspectives

Abstract

Chronic obstructive pulmonary disease (COPD) remains a leading cause of death worldwide, yet only one new drug class has been approved in the last decade. However, resurgence in COPD treatment has been recently fueled by a greater understanding of the pathophysiology and natural history of the disease, as well as a growing prevalence and an aging population. Currently, there are nearly 25 novel drug targets in development. Furthermore, the indication has undergone some fundamental changes over the last couple of years, including an updated diagnosis paradigm, validation, and approval of patient-reported outcome questionnaires for clinical trials, and drug development tools, such as a prognostic biomarker for patient selection. In the context of clinical trials, this review aims to summarize recent changes to the diagnosis and evaluation of COPD and to provide an overview of US and European regulatory guidance. CHRONIC OBSTRUCTIVE PULMONARY DISEASE LANDSCAPE

No Independent Influence of Statins on the Chronic Obstructive Pulmonary Disease Exacerbation Rate: A Cohort Observation Study Over 10 Years

“…The stage-appropriate COPD therapy was investigated according to the recommendations of the guidelines. 20 The drug therapy of COPD is done in the earlier stages I–II according to the clinical symptoms. Asymptomatic patients do not need long-term drug therapy in these stages I–II.…”

“…In stages III–IV, patients benefit from long-term therapy with inhaled corticosteroids, ideally in combination with long-acting bronchodilators. 20 The classification of COPD was carried out in each case in this study according to the latest edition of the International Classification of Diseases (ICD J44.0−J44.9). 21…”

Long-term effect of α1-antitrypsin augmentation therapy on the decline of FEV1in deficient patients: an analysis of the AIR database

“…Even though the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) guidance for new drug studies in COPD have determined that the FEV 1 should be the primary outcome in drug development [ 27 ], the findings in our study suggest that FEV 1 decline would be inappropriate to evaluate the effect of AAT augmentation therapy in ZZ-AATD patients. Historically, AAT augmentation therapy with a dose of 60 mg·kg −1 has been introduced based on the hypothetical effect on reducing FEV 1 decline by restoring the protease–antiprotease balance through AAT substitution.…”

“…Agency (EMA) guidance for new drug studies in COPD have determined that the FEV 1 should be the primary outcome in drug development (27), the findings in our study suggest that FEV 1 decline would be inappropriate to evaluate the effect of AAT augmentation therapy in ZZ-AATD patients.…”

Moving to a Personalized Approach in Respiratory Medicine. From Academic Research to Regulatory Intervention

“…There is, therefore, an urgent and essential need to develop measures that at least better assess meaningful outcomes for patients (including effects on symptoms and quality of life). In asthma and COPD, there is more evidence about the clinical outcome measures to be used, with constructive input from different regulatory authorities (Haarst et al, 2019;Collacott et al, 2021). However, there is still a need for a standardized approach to the assessment of asthma/COPD symptoms and their impact on heath related quality of life (HRQoL) from the patient's perspective.…”