Cystic Fibrosis is a life-limiting genetic disease that affects many organs in the body, particularly the lungs.  People with CF (pwCF) have a range of symptoms including, breathlessness, sputum production and the inability to effectively digest food.  Additional complications include liver failure, diabetes, bone disease and infertility.  Until recently, treatments have been focused on symptom control, however, during the last decade, the work of the Queen’s University Belfast CF Research Team has been at the forefront of major advancements in drugs targeting the underlying genetic deficit.

There are over 80,000 people living with Cystic Fibrosis globally.  Of those 10,500 are in the UK and account for 9,500 hospital admissions and over 100,000 bed days a year.  The condition is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene which is responsible for the regulation of salt and water levels in the body.   

WWIEM’s Dr Damian Downey and Professor Stuart Elborn have worked for over 12 years supporting the development of drugs that improve the function of CTFR.  Extensive clinical trial experience coupled with the Clinical Trial Network infrastructure (established by Queen’s and the Belfast Health and Social Care Trust) resulted in them playing a pivotal role in a drug development programme working alongside Vertex Pharmaceuticals to deliver trials for single, double and triple therapies in CF.   The culmination of years of drug development resulted in the world’s first trials of “triple therapy” for CF.  Dr Downey was the UK lead for the phase 3 clinical trials of Elexacaftor-Tezacaftor-Ivacaftor (Trikafta [US]/Kaftrio [EU]) in 2018.  A study in pwCF with two copies of the F508del mutation reported a significant increase in lung function (ppFEV₁ of 10%) between pwCF receiving Trikafta/Kaftrio in comparison to those receiving Symdeko.

The most recent trials successfully demonstrated that a combination of drugs can treat up to 90% of pwCF by addressing the underlying cause of their disease.  This new “triple therapy” results in a significant improvement in lung function and quality of life and also reduces the frequency of chest infections.  Both the Food and Drug Administration and the European Medicines Agency approved Trikafta/Kaftrio for use in 2020.  Trikafta/Kaftrio was hailed as a “landmark approval” by the FDA having an expedited approval process including Priority Review, Fast Track, Breakthrough Therapy, and orphan drug designation.

The most important impact of the QUB research is the benefit to pwCF treated with the therapies described above.  Evidence from the phase 2 and phase 3 trials in which Dr Downey and Professor Elborn acted as Chief Investigator or Co-Chief Investigators clearly demonstrated the transformative effect of these breakthrough therapies.  Dr Downey’s joint role within Queen’s and the NHS has allowed him to lead the introduction of Kaftrio in Northern Ireland ensuring that over 90% of the CF population have access to this CFTR modulator therapy.

Delivery of the trials in Belfast has brought huge benefits to the local population of pwCF and provided early access to treatments not yet available as part of standard care.  Trial results showed improvements in key outcomes, for example, lung function, sweat chloride (an in-vivo marker of CFTR function), quality of life and bodyweight.  Results from a Trikafta/Kaftrio trial also showed a reduction in pulmonary exacerbations of 63%.

These improvements in clinical outcomes have huge personal significance to pwCF as it allows them to regain some aspects of normal life without weeks spent in hospital and allowing them to spend time with their families.