Revolutionary new treatment underpinned by research led by Leicester is transforming the
lives of severe asthma sufferers.
Over 4 million people are prescribed asthma therapies in the UK, and it remains responsible
for more than 1,400 deaths per year. The vast majority of patients with asthma have a mild
to moderate disease, but around 5% of all cases are classed as ‘severe’.
Patients with severe asthma have symptoms that negatively affect their quality of life,
despite daily therapy with corticosteroids delivered through an inhaler, and frequently seek
medical help due to their condition.
Over the last two decades, studies into the biology of severe asthma carried out by a global
team led by Professor Brightling at the NIHR Leicester BRC have led to a number of
antibody-based therapies which have revolutionised management of the serious condition.
Their focus has been on understanding the biological processes that lead to inflammation
and mucus building up in the lungs of people with severe asthma; what causes this, and how
we could potentially stop it.
On looking closely at the genetics and lung tissue samples of people with severe asthma,
the Leicester researchers were the first to recognise that a substance called thymic stromal
lymphopoietin (TSLP) increases the risk of someone having severe asthma and is closely
involved in the inflammation in the airway in asthma.
The ‘biologic’ monoclonal antibody, tezepelumab which is given as a monthly injection,
specifically targets TSLP.
In the initial clinical studies (published in 2021 and 2023) tezepelumab, which has been
commercialised in the UK by AstraZeneca, reduced asthma attacks by more than 50%. Not
only that but the number of attacks which led to hospitalisation reduced by over 80% with
participants showing improvement in inflammation and breathing tests.
Research published in September 2023, in the New England Journal of Medicine evidence:
Evidence has shown in CT scans of the chest that tezepelumab reduces the number of
airways that are plugged or blocked by mucus. This improvement in mucus plugging was
linked to improvements in inflammation and lung function.
In the trial, 82 participants had CT scans to observe mucus plugs at week zero and week
28.
Thirty-seven participants were given tezepelumab after the first scan, and once every 4
weeks for the duration of the study. The remaining participants were given a placebo.
The Leicester researchers found that mucus plugs were present in 57% of patients before
they were treated with tezepelumab which reduced to 22% of patients after treatment.
The proportion of patients with mucus plugs who received the placebo did not change
significantly (mucus plugs were present in 31% of patients before receiving a placebo, and in
33% of patients after receiving placebo).
Reductions in mucus plug scores with tezepelumab were also associated with improvements
in lung function and inflammation.
Tezepelumab was licensed by FDA at the end of 2022 and was approved by NICE in April
2023 for use in the UK as an adjunctive treatment for severe asthma in individuals aged 12
years and over, when treatment with high-dose inhaled corticosteroids plus another
maintenance treatment has not worked well enough.
As well as improving management of severe asthma, this Leicester research has informed
clinical guidelines for the condition globally.
At the time of writing (May 2024) Tezepelumab is the most prescribed first biologic in many
regions of the world, improving the management of the condition for thousands of patients.
How this research led to the development of the biologic, and the story of patient David
Chapman who took part in the research, was featured in BBC One’s Morning Live on 16
November 2023. The piece engaged the national TV audience with the advances in
treatment for severe asthma, and highlighted the benefits of taking part in research,
increasing the impact of this work still further.
As an NIHR Biomedical Research Centre, our mission is to take findings from the laboratory
and deliver them into new treatments for patients. To see this new medicine come full circle
and be prescribed in our severe asthma clinic based at Glenfield Hospital (University
Hospitals of Leicester NHS Trust), where this research programme started, is incredibly
special. This wouldn’t have been possible without the infrastructure than NIHR funding
provides – for our people and places, and support networks it brings.
*Phase 3 NAVIGATOR study – Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma, May 2021, New England Journal of Medicine 384(19):1800-1809 ** New England Journal of Medicine Evidence