The lexicon of lung disease has been developing over four centuries from its early livid descriptions such as turgid, voluminous and catarrh coined by physicians navigating various airflow restrictions now known as Chronic Obstructive Pulmonary Disease (COPD).
Its science and vocabulary have progressed to keep pace with disturbing rises in morbidity and mortality – the World Health Organization estimated that 251 million cases of COPD were registered in 2016 that resulted in 3.17 million deaths globally.
Other patient and clinical interest groups put the figure even higher, with the European Respiratory Society placing the number at 300 million, with figures rising higher in nations with poor access to spirometry, essential medications and pulmonary rehabilitation services.
COPD jumped up the health agenda and GSK believes it is at the forefront of approaches that will revolutionise the management and treatment of a range of respiratory diseases and subtypes with an enhanced personalised delivery.
The promise includes a vaccine, which will report on phase 2 trials later this year, continuing work to identify biomarkers, and the start of a phase 3 trial of its therapy mepolizumab to treat COPD exacerbations with eosinophilic inflammation.
Professor Neil Barnes, the company’s Global Clinical Science Lead for COPD, posits that 2020 is a landmark year as the company aims to make positive progress on the road to reducing mortality and easing the strain on patients whose breathing and lives are blighted by the condition.
“Ever since I’ve been doing respiratory medicine, there has been the need for biomarkers to understand how to treat the right patient with the right medicine,” said Professor Barnes, who joined the company in 2013 after a distinguished clinical career as Consultant Respiratory Physician at London Chest Hospital, Barts Health NHS Trust, in London, UK.
Treatable traits
“Although that desire has been there, we haven’t been able to do it until recently. But I think the work that we’ve done in collaboration with academia has demonstrated that there are various characteristics, called treatable traits, where you can identify patient groups that are doing very well and you can also identify patients with ongoing, unmet need. That actually helps clinicians make decisions about which treatment is most appropriate for which patient.
“I knew about GSK’s portfolio of drugs and it was clear the company had the desire to commit to important trials, which answer important questions, which is one of the main reasons I came across to industry from clinical practice.”
The push has been to graduate from existing therapies which aim to improve lung function and reduce inflammation to targeting new mechanisms to achieve more personalised care.
The company’s suite of COPD advances, combined with evolutions in scientific understanding, have illuminated that COPD has two main treatable traits – airflow obstruction (bronchoconstriction) and narrowed airways (inflammation) – enabling clinicians to have more refined therapy approaches to treat the underlying condition driven by eosinophils.
For example, evidence now suggests that around 80% of patients have a blood eosinophil count that indicates they may benefit from a steroidcontaining treatment.
“The emergence of eosinophil counts as a biomarker in COPD has been helpful. It means that clinicians can potentially use a very simple test to determine the likelihood of patients responding to different treatments,” added Professor Barnes. “It gives more certainty that you are likely to get a good response and it indicates patients who will respond versus those who don’t need a particular treatment, which clearly helps in clinical decision-making.
Developing clarity
“COPD has not had the benefit of a unified treatment approach similar to that deployed in, for example, cardiac or TB medicine. For instance, in the UK, US, Canada and Spain, the first treatment was an ICS/LABA, such Seretide or Symbicort, while in Germany it was a bronchodilator. When you see different treatment patterns in different countries, it indicates there is no clarity about treatment and the research hasn’t shown a clear pathway. But we have developed greater clarity now thanks to the studies that we’ve done. We are now better able to demonstrate which patients do better with which particular treatments.
“It takes time to change practice but we are heading in the right direction.”
The exacerbations that taint a huge number of COPD patients are now being addressed with more vigour, he added.
“We’ve identified that about 60-70% of COPD exacerbations are related to infections, usually viral infections, which then trigger bacterial infections,” said Professor Barnes. “There is a big challenge to find ways of preventing those infections. GSK had a number of possible leads that, unfortunately, didn’t work out but there is an optimism in vaccines that can target the mechanism, which can be a common cold or flu which breaks down your defence and allows bacteria to grow.
“You would imagine coronavirus would be one of those threats.”
GSK is trialling its biologic anti IL-5 drug mepolizumab, licensed for severe asthma, in eosinophilic COPD with a new phase 3 trial having recently started. The company is also forging ahead with biologics research in asthma, particularly targeting the IL-33 pathway.
Research focus
“I set up and ran a severe asthma clinic for 25 years and, although they represent only 5-10% of the asthma patients, they have a terrible time. You have to treat them with steroids with all the potential side effects,” he added. “Asthma has slipped down the healthcare agenda but, importantly, we are getting far fewer admissions and deaths from asthma than we used to, in developed countries at least. But there is still an unmet need for lots of asthma patients who find the condition impacts their lifestyle, family work and education. There is a lot of work and research still to be done.
“This year, COPD is predicted to become the third leading cause of death worldwide, after heart conditions and cancer, which really puts it on the health radar and underscores why this research is so important.”
The COPD Foundation, a not-for-profit organisation that features GSK, AstraZeneca, Pfizer, Mylan and Boehringer Ingelheim among its members, was established to raise the profile of the condition and accelerate innovations. Its work has concentrated global attention on COPD and encouraged a range of research.
GSK is proud of its pioneering partnerships and research programmes that have shared data across the industry as it racked up four new medicine launches in four years, leading to better symptom management and reduced mortality.
“COPD was a Cinderella disease when I started in respiratory medicine but it is certainly not that now,” said Professor Barnes. “When healthcare systems saw the data and recognised the two commonest reasons people are admitted to hospital are exacerbations of COPD and cardiac problems, it recognized the issues and improved the focus.
“We are working to make sure that focus continues along with research.”