In recent weeks there has been a buzz around a new treatment breakthrough: benralizumab, which in a study published in the Lancet Respiratory Medicine Journal has gained traction for producing better clinical outcomes in patients with asthma and chronic obstructive pulmonary disease (COPD) presenting with acute exacerbations compared to the current standard of care. Now what does this all mean? Let me unpack it for you.

Allergic asthma is a well-known hypersensitivity condition where the immune system is extra sensitive to foreign substances, so much so that immune responses can happen even in the absence of any obvious trigger. COPD is the term given to a group of lung conditions that cause breathing problems. Both conditions are chronic, and in both exacerbations can occur where there are acute immune responses leading to inflammation in and narrowing of the airways, heightening breathing difficulties. In many cases the immune responses involved in exacerbations include the recruitment and activation of eosinophils, a type of white blood cell that is very effective at causing mass inflammation. Benralizumab targets eosinophil action to reduce inflammation. 

Benralizumab, marketed under the name Fasenra and developed by AstraZeneca, is a humanised monoclonal antibody. Antibodies are messengers in the immune system important for the detection of previously encountered antigens (molecules that generally come from a harmful microorganism, but in the case of hypersensitivity conditions like asthma, they can be non-harmful agents such as dust) and the subsequent activation of a part of the immune system that can get rid of the antigen. Humanised monoclonal antibodies are synthetic antibodies made by combining parts of a human antibody with a mouse or rat antibody. The mouse or rat portion is developed to bind to a single part of a specific antigen, with the human part of the antibody allowing it to work without the human body registering it as a foreign substance. Monoclonal antibody drugs are a relatively novel treatment type, with their usage having big impacts in cancer and autoimmune condition treatment.

Benralizumab acts against part of the receptor for the cytokine interleukin-5 (IL-5), a messenger molecule of the immune system. This receptor is important in the activation and survival of eosinophils and other effector immune cells. By binding to the receptor, benralizumab interferes with IL-5 receptor binding, which reduces eosinophil survival. Decreased eosinophil levels in exacerbations results in less inflammation and so less obstruction of airway function, making breathing easier. In the study, they found that respiratory symptoms in the patients admitted with eosinophil-mediated acute exacerbations treated with benralizumab were reduced and that they had significantly fewer treatment failures than the cohort using the standard of care alone, meaning that the treatment took longer to fail and a higher quality of life was reported after the hospital event. 

"Monoclonal antibody drugs are a relatively novel treatment type, with their usage having big impacts in cancer and autoimmune condition treatment"

Neither asthma or COPD can be cured, and so treatments involve management of symptoms and minimising exacerbations to prevent disease progression and protect the lungs from further damage. Currently the protocol (the ‘standard of care’) for patients admitted into A&E departments with acute exacerbations of severe asthma and COPD is the administration of steroids (a class of antiinflammatory drugs), which doubles as a preventative medicine for severe asthma to avoid exacerbations. Steroids for these purposes are outdated medications, as while they work to ease breathing they are short acting and so have to be taken regularly, which can hinder patient adherence to treatment. Side effects of heavy duty steroid use include weight gain, extreme fatigue and bone demineralisation (weakening), which are more likely in patients with severe asthma and COPD, as the chronic nature of the conditions makes long term steroid use more common. Aside from this, steroids are usually administered using inhalers, which have a big environmental impact, as the gases used within them are powerful greenhouse gases, making them the single largest contributor to the NHS carbon emissions of any medicine. In addition, patients often only receive more advanced treatment (like steroids) for their condition after experiencing the exacerbation or being hospitalised. In comparison to the current standard treatments, benralizumab is longer-acting and is administered by injection instead of inhalers, making it a greener and more prevention-focused alternative to steroid treatments. 

"steroids are usually administered using inhalers, which have a big environmental impact, as the gases used within them are powerful greenhouse gases, making them the single largest contributor to the NHS carbon emissions of any medicine"

This is all well and good, a new standard of care contender on the scene!... Until you take a step back and realise that this has been one of the only clinical breakthroughs in respiratory medicine for the better half of a century, despite four of the top six causes of death worldwide in 2021 relating to the respiratory system. Surely this would be grounds for increased research focus, no? 

In addition to the lack of clinical advancement in the field, current (outdated) treatments for respiratory conditions are not practical for the NHS. Published in the NHS Prescription Cost Analysis 2023/24, the respiratory system was in the top five categories for items dispensed, with the first being the cardiovascular system. Out of these 5 categories, the respiratory system had the most expensive average for popular prescriptions with a mean cost of £16.47 per item. This is a whole £13.35 difference from the mean cost per item of £3.12 for the cardiovascular system. Along with this, the chemical substance beclometasone dipropionate - found in brown inhalers - incurred the highest cost of any medication in the NHS in 2023, indicating how the cost of treatment has not reduced in line with demand. 

"this has been one of the only clinical breakthroughs in respiratory medicine for the better half of a century, despite four of the top six causes of death worldwide in 2021 relating to the respiratory system"

One reason is that respiratory research is underfunded: in the UK Health Research Analysis Report 2022, the respiratory system was the 8th highest specific health category for funding distribution from HRCS, equating to around 2.5% of the total spend on healthcare disciplines. This proportion of research funding was a 14.5% difference from the top specific health category. However, more damning has to be the fact that research funding for the respiratory system was significantly lower than the comparative burden of disease, and this mismatch has not improved in over a decade. 

Bearing the brunt of this burden are the populations most at risk of developing respiratory conditions: in the context of asthma and COPD this would be children and older adults that smoke or inhale toxic particles, mostly due to work environments and living in areas of high pollution. For these reasons, lung diseases are often termed ‘diseases of poverty’, as increased disease progression is more likely in people with lower incomes due to often working longer hours, having less free time to take care of themselves and other household members, and being under worse living conditions where mould and allergens are more prevalent (especially bad for children). This can mean less preventative and maintenance treatment and so more hospital trips and higher frequency of exacerbations, leading to accelerated condition progression and a lower quality of life. In these populations, the impact of respiratory conditions can be greater, as constant life disruption in school or work can impact academic and career progression, which can increase inequity by reducing productivity and disrupting lifestyles. 

In a rapidly advancing modern world, the risk factors for respiratory conditions such as asthma are only going to increase, so it is only right that research into treatments and prevention of respiratory conditions follow this trend. Benralizumab and other novel treatments can hopefully help rewrite common practice away from old fashioned treatments and help find better preventative and long term solutions to respiratory conditions to help ease the burden on the NHS and on the populations of people around the world that they affect.