Tackling underlying respiratory conditions for this pandemic and next

During the COVID-19 pandemic, one of the many phrases that has become irreversibly etched onto the minds of the British public – along with social distancing, self-isolation and R number – is 'pre-existing health condition'.

As Government press conferences brought home the tragic volume of lives shortened, those four words were a daily reminder that the pandemic was not, unlike some misguided claims, a leveller. The fact is COVID-19 has targeted those who, in some way or other, already had health issues of varying complexity.  

As governments, healthcare agencies and science and technology innovation bodies wrestle with how to better prepare the world for the – sadly inevitable – next pandemic, concrete action that can be taken now is to both tackle those conditions with an unmet critical need that may make people vulnerable in future epidemics.

One of the major concerns here is non-cystic fibrosis bronchiectasis (NCFB). A condition not known widely outside those that come in to immediate contact with it, there is emerging evidence showing that NCFB is far more common than previously thought and is viewed as a severe comorbidity of chronic obstructive pulmonary disease (COPD). It is estimated by the British Lung Foundation that in excess of 300,000 people could be living with bronchiectasis in the UK.

What is non-cystic fibrosis bronchiectasis (NCFB)?

NCFB is a long-term condition where the airways become abnormally widened, leading to a build-up of excess mucus that can make the lungs more vulnerable to repeated, serious infections.

The most common symptoms of bronchiectasis include a persistent cough that usually brings up phlegm (sputum) and breathlessness. Airways are further damaged by each infection, and over time that can cause reduced oxygen reaching vital organs.

Millions of patients worldwide are at risk of this condition, and as of yet there is no approved preventative therapy. The condition can also get worse, quickly – in severe cases there can be multiple exacerbations a year. Patients can become chronically infected with the superbug Pseudomonas aeruginosa (Pa), significantly reducing their quality of life and survival prospects.

Up to 30% of these chronic sufferers are colonised with Pa, which results in a poor quality of life and significantly increases morbidity and mortality risks. Additionally it also leads to an 87% increase in the total healthcare cost per patient. In the USA, for example, the average cost increases from $36,213 to $67,764 per patient per year when Pa takes hold

Bronchiectasis as an underlying condition exacerbates COVID-19

A study published in The Lancet reported patients with bronchiectasis are at a higher risk of showing COVID-19 symptoms or having a more severe infection than others. Many patients also feel uncomfortable wearing masks due to the requirements of living with a chronic respiratory health condition, while there is a fear in some with the condition that being hooked up to a ventilator – if required – could cause further harm to already damaged lungs.

While a range of factors have contributed to the North West suffering high mortality rates during the pandemic – and there are now real concerns about what the impact of long COVID will have for our region – there is a world-leading initiative in place which means it is in a unique position to be at the forefront of using its strengths within both the private and public sector to tackle health inequalities while helping to rebuild the UK economy.

The Infection Innovation Consortium (iiCON) aims to reduce global burden of infectious disease

Infex Therapeutics is a proud founder member of iiCON, the Infection Innovation Consortium headed by the Liverpool School of Tropical Medicine, which received £18.6 million from UK Research and Innovation Strength in Places Fund and serves to bridge the gap in the R&D ecosystem between industry, academia, and the NHS, to accelerate and support the discovery and development of innovative new anti-infectives.

iiCON's collaborative effort is directly reducing the global burden of infectious disease with a co-ordinated initiative to address key roadblocks in global R&D pipelines and strengthen and regenerate the global anti-infectives supply chain.

The consortium is developing a leading global centre for infectious disease R&D in the North West of England as part of a £173.4 million programme. This capitalises on the region’s renowned track record in working on active translational programmes in vaccines, diagnostics, therapeutics and antiviral formulations.

Working together to develop a treatment for bronchiectasis

Through iiCON, Infex Therapeutics’ RESP-X programme is undertaking a Phase 1 clinical evaluation of a novel monoclonal antibody for the treatment of Pa infections in bronchiectasis patients.

RESP-X is an immune-infection therapy being developed in partnership with Japanese pharma company Shionogi. It is designed as a preventative treatment against NCFB that will help the body tackle Pa infections, a hard to treat drug-resistant pathogen recognised by the WHO as a critical threat to human health. A novel humanised monoclonal antibody, RESP-X does not kill bacteria directly but deactivates am inflammation mechanism that allows the patient’s own immune system to act against the infection.

The need to develop a treatment for bronchiectasis is becoming more pressing, with 90,000 new patients identified in the UK between 2012 and 2020. There are specialist NCFB clinics in all major UK cities, with several in London. Each clinic has between 5,000 and 10,000 NCFB patients under routine monitoring.

Across the UK, between 25% and 30% of those patients have had a positive Pa diagnosis, rising to 50% in Liverpool – mirroring the health inequalities exposed by the COVID-19 pandemic. Yet these patients can be assured that scientists in the North West are determined to deliver treatments that will vastly improve their quality of life.

The Liverpool School of Tropical Medicine (LSTM) and Liverpool University Hospital Foundation Trust are key members of the iiCON project team that is working with us to deliver the first RESP-X clinical trial later this year that that will determine the safety and tolerability of this new treatment for people living with bronchiectasis.

Working together, we want to enhance patient outcomes and reduce the healthcare costs associated with exacerbations. The product we are developing is not an antibiotic and so would reduce the use of such antibiotics and help stem the tide of antibiotic resistance. There is an existing and motivated patient population and a network expert doctors who we look forward to working with on this groundbreaking project.

We are therefore hugely excited about what our RESP-X programme can potentially achieve for patients with bronchiectasis. As the COVID-19 pandemic has laid bare, pre-existing conditions can be devastating when coming into contact with an unpredictable infectious disease – we’re determined to use exceptional resources in the North West to ensure patients with bronchiectasis are better placed than ever to live better and longer lives.

Author: Dr Peter Jackson is executive director, Infex Therapeutics