COPD: Therapies on the Cusp


Clinical trials in this area reflect new science, and corresponding challenges in their execution.

Deepika Khedekar, Mpharm, Clinical Trial Clinical Trial Lead, IQVIA

Deepika Khedekar, Mpharm, Clinical Trial Clinical Trial Lead, IQVIA

Over 3 million people die globally each year due to Chronic Obstructive Pulmonary Disease (COPD), according to a report published by the American Journal of Respiratory and Critical Care Medicine.1 To put it in perspective, that's equivalent to the entire population of Qatar—a startling reminder of the magnitude of this global health crisis. Recent findings from the American Lung Association paint a distressing picture, with 12.5 million new cases diagnosed2 and 148,5123 deaths recorded in the United States alone in 2020. While clinical trials may hold the potential to reshape the trajectory of COPD globally, it's crucial to understand the nature of COPD and its established causes.

COPD is a progressive lung condition characterized by persistent airflow limitation, making it difficult to breathe. The primary cause of COPD is long-term exposure to irritants that damage the lungs, with cigarette smoke being the most common culprit. Other potential causes include exposure to secondhand smoke, air pollution, occupational hazards (such as chemicals or dust), and genetic factors, particularly a deficiency in the protein alpha-1 antitrypsin.

In the United States, COPD encompasses two main conditions: emphysema and chronic bronchitis. Emphysema occurs when the walls between air sacs in the lungs are damaged, impeding their elastic function. This makes it challenging for the lungs to expel air effectively. Chronic bronchitis, on the other hand, results from persistent irritation and inflammation of the airway lining, leading to the production of thick mucus and obstructed breathing. While many individuals with COPD experience both emphysema and chronic bronchitis, the severity of each condition varies from person to person.

According to data from the WHO International Clinical Trials Registry Platform (ICTRP)4, there are over 600 clinical trials for COPD currently recruiting patients. These trials include investigational drugs, gene therapies, and devices.

One notable example is a clinical trial conducted by Sanofi and Regeneron targeting COPD.5 Their investigational drug Dupixent works by blocking the activity of two proteins called interleukin-4 (IL-4) and interleukin-13 (IL-13), which are responsible for kickstarting inflammatory response in patients diagnosed with COPD. In March 2023, the two companies announced positive results from a Phase III clinical trial of Dupixent in COPD patients. The trial showed that Dupixent reduced COPD exacerbations by 30% and improved lung function.5 If approved by the FDA, this pivotal drug would be the first biologic medicine cleared to treat the lung disorder.

Another example is a research program at Penn Medicine that led to the development of an innovative device to treat COPD known as the endobronchial valve.6 These minimally invasive valves are small devices placed in the airways to treat conditions like emphysema and COPD. They work by redirecting airflow away from damaged parts of the lung, allowing healthier areas to function better. The valves create a one-way flow, enabling trapped air to escape during exhalation while preventing new air from entering the damaged areas during inhalation. This helps restore balanced airflow, improves lung function, and alleviates symptoms. This clinical research study brings hope for advanced and minimally invasive device-based therapies for patients diagnosed with COPD.

Scientists from the University of Pennsylvania's Perelman School of Medicine have identified a new type of cell in human lungs called respiratory airway secretory cells (RASCs).7 The discovery, reported in the journal Nature, suggests that RASCs have regenerative abilities and could potentially replenish another group of cells involved in COPD). The researchers found that RASCs produce proteins necessary for the mucus lining in the airways. They also found that RASCs are similar to another type of cell called alveolar epithelial type 2 (AT2) cells, which are stem cells for the lung's air sacs. In people with COPD, the function of AT2 cells is impaired, suggesting a potential role for RASCs in treating the disease. The discovery of RASCs in the lungs has the potential to greatly speed up the progress of clinical trials focused on COPD and could pave the way for new treatments that specifically target these cells to restore normal lung function.

Challenges in COPD clinical trials

Although there have been notable advancements in COPD clinical trials, several challenges in their design and implementation exist. COPD is a heterogeneous disease with various subtypes and underlying mechanisms. This can make it difficult to interpret the trial results, as the drug may work well for one subtype but not for others. For example, a drug may be effective in reducing symptoms in patients with chronic bronchitis but not in those with emphysema. Designing clinical trials that account for these differences and identifying the appropriate patient population can be complex.

This is partly due to current methods to detect COPD, which are subjective. The spirometry test used by doctors to assess lung strength can lead to different interpretations and conclusions among medical professionals, even with the same test results. For example, in a multi-center COPD trial, different investigators may interpret spirometry results differently, leading to inconsistent patient selection. One investigator may diagnose a patient with COPD based on a certain spirometry result, while another investigator may not. This can result in a heterogeneous study population, making it difficult to draw meaningful conclusions from the trial.

Secondly, COPD clinical trials often involve long-term treatment regimens and follow-up visits. Ensuring patient adherence to the trial protocol, including medication usage and attendance at study visits, can be challenging. Defining and measuring relevant outcomes poses another challenge in these clinical trials. While common endpoints include lung function, exacerbations, quality of life, and symptom improvement, selecting appropriate and meaningful endpoints that accurately reflect treatment effectiveness can be a matter of debate. Moreover, COPD often coexists with other comorbid conditions, such as cardiovascular disease, diabetes, and depression. Managing these comorbidities and considering their impact on trial outcomes adds complexity to trial design and the interpretation of results.

Additionally, the chronic nature of COPD necessitates long-term management and follow-up in clinical trials. Retaining patients in the study and collecting reliable long-term data pose logistical and financial challenges. And finally, COPD management involves various treatment modalities, including inhalers, pulmonary rehabilitation, and pharmacotherapy. Standardizing interventions across multiple trial sites to ensure consistency and comparability can be challenging.

Modern solutions for COPD clinical trials

Addressing the challenges in COPD clinical trials requires a multifaceted approach that involves careful planning, robust trial design, and efficient trial operations. To account for the heterogeneity of COPD, trials can stratify patients based on their subtype and severity of COPD, ensuring that each stratum has enough patients to detect a statistically significant difference in outcomes. Additionally, standardizing the spirometry procedure and interpretation across all sites can help reduce the subjectivity in detecting COPD. Providing training to all investigators on how to conduct spirometry and interpret the results, as well as developing a centralized system to review and validate all spirometry results, can ensure consistency in patient selection and assessment of lung function.

To ensure patient adherence to long-term treatment regimens and follow-up visits, trials can implement strategies such as simplifying treatment regimens, providing patient education, conducting regular follow-ups, sending reminders, offering incentives, and involving caregivers. These strategies can help monitor adherence, address any concerns or barriers, and provide ongoing support to patients.

Defining and measuring relevant outcomes in COPD trials can be addressed by selecting appropriate and meaningful endpoints that accurately reflect treatment effectiveness. This may involve using a combination of endpoints, such as lung function, exacerbations, quality of life, and symptom improvement, to provide a comprehensive assessment of treatment effects. Managing comorbidities in COPD trials can be addressed by considering their impact on trial outcomes and incorporating appropriate adjustments in the trial design and analysis.

To address the challenges of long-term management and follow-up in COPD trials, retaining patients in the study and collecting reliable long-term data can be achieved through strategies such as providing incentives for continued participation, offering flexible follow-up options, and using electronic data capture systems to facilitate data collection. Standardizing interventions across multiple trial sites can be achieved by developing detailed protocols, providing training to site staff, and conducting regular monitoring to ensure consistency and comparability of interventions.

In conclusion, addressing the challenges in COPD clinical trials requires a combination of strategies that involve careful planning, robust trial design, and efficient trial operations. By implementing these strategies, we can overcome the obstacles and conduct high-quality COPD trials that provide valuable insights into the treatment and management of this chronic respiratory condition.


  1. Halpin DMG, Vogelmeier CF, Agusti A. Lung Health for All: Chronic Obstructive Lung Disease and World Lung Day 2022. American Journal of Respiratory and Critical Care Medicine. 2022 Sep 15;206(6):669-671. doi: 10.1164/rccm.202207-1407ED. PMID: 36112775; PMCID: PMC9799120.
  2. COPD Trends Brief: Prevalence, 2023.
  3. COPD Trends Brief: Mortality, 2023.
  4. World Health Organization, ICTRP Search Portal.
  5. Press Release: “Dupixent® demonstrates the potential to become the first biologic to treat COPD by showing a significant reduction in exacerbations in the pivotal trial,” March 23, 2023.
  6. “COPD: Breathing Easy without Major Surgery: An Interview with Kevin Ma, MD, Penn Medicine,” July 30, 2021.
  7. “With newly discovered cell type, Penn scientists propose COPD drug development strategy,” Fierce Biotech, April 5, 2022.
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