Review of Drug Development Guidance to Treat Chronic Obstructive Pulmonary Disease:  US  and  EU  Perspectives

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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.

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Most cited references 71

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Susceptibility to exacerbation in chronic obstructive pulmonary disease.

John R. Hurst, Jørgen Vestbo, Antonio Anzueto … (2010)

Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)

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Lebrikizumab treatment in adults with asthma.

Jonathan Corren, Robert Lemanske, Nicola Hanania … (2011)

Many patients with asthma have uncontrolled disease despite treatment with inhaled glucocorticoids. One potential cause of the variability in response to treatment is heterogeneity in the role of interleukin-13 expression in the clinical asthma phenotype. We hypothesized that anti-interleukin-13 therapy would benefit patients with asthma who had a pretreatment profile consistent with interleukin-13 activity. We conducted a randomized, double-blind, placebo-controlled study of lebrikizumab, a monoclonal antibody to interleukin-13, in 219 adults who had asthma that was inadequately controlled despite inhaled glucocorticoid therapy. The primary efficacy outcome was the relative change in prebronchodilator forced expiratory volume in 1 second (FEV(1)) from baseline to week 12. Among the secondary outcomes was the rate of asthma exacerbations through 24 weeks. Patient subgroups were prespecified according to baseline type 2 helper T-cell (Th2) status (assessed on the basis of total IgE level and blood eosinophil count) and serum periostin level. At baseline, patients had a mean FEV(1) that was 65% of the predicted value and were taking a mean dose of inhaled glucocorticoids of 580 μg per day; 80% were also taking a long-acting beta-agonist. At week 12, the mean increase in FEV(1) was 5.5 percentage points higher in the lebrikizumab group than in the placebo group (P = 0.02). Among patients in the high-periostin subgroup, the increase from baseline FEV(1) was 8.2 percentage points higher in the lebrikizumab group than in the placebo group (P = 0.03). Among patients in the low-periostin subgroup, the increase from baseline FEV(1) was 1.6 percentage points higher in the lebrikizumab group than in the placebo group (P = 0.61). Musculoskeletal side effects were more common with lebrikizumab than with placebo (13.2% vs. 5.4%, P = 0.045). Lebrikizumab treatment was associated with improved lung function. Patients with high pretreatment levels of serum periostin had greater improvement in lung function with lebrikizumab than did patients with low periostin levels. (Funded by Genentech; ClinicalTrials.gov number, NCT00930163 .).

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Epidemiology of COPD.

P. Girodet, C Raherison (2009)

Chronic obstructive pulmonary disease (COPD) is responsible for early mortality, high death rates and significant cost to health systems. The projection for 2020 indicates that COPD will be the third leading cause of death worldwide (from sixth in 1990) and fifth leading cause of years lost through early mortality or handicap (disability-adjusted life years) (12th in 1990). Active smoking remains the main risk factor, but other factors are becoming better known, such as occupational factors, infections and the role of air pollution. Prevalence of COPD varies according to country, age and sex. This disease is also associated with significant comorbidities. COPD is a disorder that includes various phenotypes, the continuum of which remains under debate. The major challenge in the coming years will be to prevent onset of smoking along with early detection of the disease in the general population.

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Author and article information

Contributors

Aernout van Haarst: aernout.vanhaarst@celerion.com

Journal

Journal ID (nlm-ta): Clin Pharmacol Ther

Journal ID (iso-abbrev): Clin. Pharmacol. Ther

Journal ID (doi): 10.1002/(ISSN)1532-6535

Journal ID (publisher-id): CPT

Title: Clinical Pharmacology and Therapeutics

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Print): 0009-9236

ISSN (Electronic): 1532-6535

Publication date (Electronic): 23 July 2019

Publication date (Print): December 2019

Publication date PMC-release: 23 July 2019

Volume: 106

Issue: 6 , Placebo Response ( doiID: 10.1002/cpt.v106.6 )

Pages: 1222-1235

Affiliations

[ ¹ ] Scientific Affairs Celerion Lincoln Nebraska USA

[ ² ] Centre for Experimental Medicine School of Medicine Dentistry and Biomedical Sciences Queen's University Belfast UK

Author notes

[*] [* ]Correspondence: Aernout van Haarst ( aernout.vanhaarst@ 123456celerion.com )

Article

Publisher ID: CPT1540

DOI: 10.1002/cpt.1540

PMC ID: 6896238

PubMed ID: 31334840

SO-VID: c16b7337-617d-4a8b-8bb0-fb80c1ebb6d7

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

History

Date received : 12 November 2018

Date accepted : 04 May 2019

Page count

Figures: 2, Tables: 3, Pages: 14, Words: 11646

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cover-date December 2019

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.2 mode:remove_FC converted:05.12.2019

Review of Drug Development Guidance to Treat Chronic Obstructive Pulmonary Disease: US and EU Perspectives

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Abstract

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Most cited references 71

Susceptibility to exacerbation in chronic obstructive pulmonary disease.

Lebrikizumab treatment in adults with asthma.

Epidemiology of COPD.

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