IFN-β (SNG001) in COPD
Chronic Obstructive Pulmonary Disease (COPD) is a lung condition characterised by airflow limitation that is not fully reversible. This airflow limitation is normally progressive and is associated with an abnormal inflammatory response of the lung to pathogenic stimulus. The majority of COPD is associated with long-term cigarette smoking. Symptoms of COPD include cough, excessive sputum production and shortness of breath.
Exacerbations of COPD are defined as the worsening of COPD symptoms beyond normal day-to-day variations and are associated with irreversible loss of lung function and, therefore, accelerated disease progression. Exacerbations severely impact on the patient’s quality of life (patients typically take a number of weeks to recover) and are a major healthcare burden, and are the second most common cause of emergency admissions to hospital1. Exacerbations are currently treated with oral corticosteroids and antibiotics. Systemic administration of corticosteroids is associated with unwanted side effects and there is a drive to reduce antibiotic usage.
Respiratory viral infections, such as the common cold and flu, are a major driver of exacerbations in patients with lung disease when infections spread from the upper respiratory tract to the lungs to worsen pre-existing lung inflammation. Furthermore, particularly in COPD, there is growing evidence that virus infections increase susceptibility to follow on bacterial infections. Therefore, there is strong rationale to develop anti-viral treatments to prevent or treat exacerbations of COPD.
Interferon beta is a naturally-occurring protein that orchestrates the body’s anti-viral defences. We have shown in in vitro models (see Figure 1 below) that interferon beta protects the lung cells of COPD patients when infected with viruses that cause exacerbations. SNG001 is a formulation of interferon beta delivered to the lung using a nebuliser.
Figure 1: IFN-ß treatment of lung cells from smokers/COPD patients cultured in the lab protects them from infection with the common cold virus.
- COPD is the 3rd leading cause of death worldwide (after heart attack and stroke)2
- US national medical costs attributable to COPD and its consequences were estimated at $32 billion in 2010 and are forecast to increase to $49 billion in 20203
- More than 15 million Americans have COPD4
- In 2010 there were 715,000 hospitalisations for COPD in the USA5
- The average cost of a hospitalisation in 2010 for a COPD patient was $7,4006
Two Phase II trials (SG005 and INEXAS) in asthma, conducted by Synairgen and AstraZeneca respectively, suggest that SNG001 boosts antiviral responses in the lungs, has a beneficial effect on lung function and, in more difficult to treat patients, improves asthma control during cold infections. However, the unexpectedly low exacerbation rate (<10%) in the INEXAS trial population suggests that the economic viability of the drug in an asthma indication would be limited.
Studies in COPD patients published in 2017 suggest that, looking at all colds in the study period, the risk that a cold will cause an exacerbation of COPD is much higher at around 50%7 and could be even higher in particular at risk patients8, making COPD a very attractive market.
However, up until now, our ability to identify those patients who may benefit from an inhaled anti-viral therapy made the design of a prospective study challenging. This is because exacerbations of COPD can be caused by other factors such as bacterial infections.
Recently, a novel point of care diagnostic tool has been developed which enables rapid confirmation of the existence of a respiratory viral infection when patients present themselves at the hospital or trial site. This enables us to treat only those patients who are infected with a virus, significantly reducing the number of subjects required to show the potential effect of SNG001. Clearly this has significant benefits in the future, allowing accurate prescribing of an anti-viral therapy quickly to those patients who could benefit from treatment.
Part one of the trial is now complete. In this part of the trial inhaled IFN-β was well tolerated in COPD patients and biomarkers of antiviral activity were significantly elevated 24 hours following IFN-β inhalation.
In March 2019 the Data Safety Monitoring Committee (DSMC) completed its planned safety review of Part 2 of the trial. In its review, the DSMC did not identify any safety concerns for patients currently enrolled and it endorsed a pre-planned broadening of the patient population to allow patients with more severe COPD to participate in the trial.
- Department of Health. An Outcomes Strategy for Chronic Obstructive Pulmonary Disease (COPD) and Asthma in England. Published July 2011.
- World Health Organisation. Available at http://www.who.int/mediacentre/factsheets/fs310/en/
- Earl S et al. Total and State-Specific Medical and Absenteeism Costs of COPD Among Adults Aged = 18 Years in the United States for 2010 and Projections Through 2020. Chest. 2015;147(1):31-45
- American Lung Association: Trends in COPD (chronic bronchitis and emphysema): Morbidity and Mortality. March 2013. Available at http://www.lung.org/finding-cures/our-research/trend-reports/copd-trend-report.pdf
- Costs for Hospital Stays in the United States, 2010. Available at https://www.hcup-us.ahrq.gov/reports/statbriefs/sb146.pdf
- Johnston NW, et al. Colds as predictors of the onset and severity of COPD exacerbations International Journal of COPD 2017:12: 839-848
- Wilkinson TMA, et al. A prospective, observational cohort study of the seasonal dynamics of airway pathogens in the aetiology of exacerbations in COPD Thorax 2017;0:1-9. Doi:10.1136/thoraxjnl=2016-209023