In March, PTC Therapeutics announced that its Phase 3 trial for Translarna (Ataluren), a new drug for some people with CF, had been unsuccessful as the benefits of the drug were not statistically significant. This means that any improvement in the health of people taking part in the trial could not be proven to be the result of the drug – they could have happened by chance.
What do Phase 3 trials do?
A Phase 3 trial is used by companies to understand the safety and any positive effects of a new medicine, technique or device in a carefully selected sample of people who could benefit from it.
Ataluren was trialled in people with CF who have at least one ‘nonsense’ mutation, which stops or significantly limits any functional CFTR protein from being created. This malfunction means that cells within many vital organs, including the lungs, digestive system and pancreas, do not transport salt chloride effectively, causing them to become clogged with thick mucus.
The drug is approved for use on the NHS for some children with Duchenne muscular dystrophy, and it had been hoped that the medicine could help some people with cystic fibrosis. However, the company announced that the two health measures they were investigating, FEV1 and pulmonary exacerbations, had not been significantly improved by using the drug. As a result, the company will stop developing this drug for use in people with cystic fibrosis.
Why do drugs fail trials?
Phase 3 trials can fail for a variety of reasons, such as the drug not being safe or not working effectively. Sometimes trials run out of money, or fail to recruit enough participants to give meaningful results. While disappointing, we can learn a significant amount from trials like this where the drug is found to be ineffective.
One major challenge for companies is that Phase 3 trials are very expensive to run, and failures are very costly. This has an impact for successful trials, where companies must look at their total expenditure when setting a price for the end product. It has been reported that over 40% of Phase 3 trials fail to progress.
Why is it beneficial even if a drug fails a clinical trial?
Clinical trials can take many years, and along the way researchers will learn a lot about the drugs and conditions they are investigating. That knowledge will help inform future research and clinical trials and improves our overall understanding of cystic fibrosis.
We believe that clinical trials are vital to realising our vision of a life unlimited by cystic fibrosis. We are committed to increasing participation and improving the quality and success of new clinical trials in cystic fibrosis.
The Cystic Fibrosis Trust’s approach to research into new treatments
Here are four ways we are helping to ensure clinical trials into new treatments for CF have the best chance of succeeding:
Developing the UK Cystic Fibrosis Registry
A key cause of Phase 3 trials failing is the recruitment of too few patients, meaning the results can’t prove the drug's effectiveness. We can use the UK CF Registry for a ‘feasibility assessment’ while the trial is still being designed, so we can understand how many people would be eligible to take part. The Registry team can also contact CF centres to help them give those eligible people the opportunity to participate.
The Cystic Fibrosis Trust is working with people with CF to design a portal into the Registry for adults with the condition that will enable them to opt in to tailor-made clinical trial alerts. Signing up to receive this personalised information will empower people with CF with knowledge about the trials they may be eligible for, based on the clinical information held about them in the database.
The Trust is also funding world-leading experts in mathematics and statistics to use the data we collect to help find out which treatments work best without such reliance on expensive, difficult and lengthy clinical trials.
Finally, the UK CF Registry is running the world's first Registry-based clinical trial in cystic fibrosis. CF-START has been funded by the National Institute for Health Research as an innovative clinical trial design that is less burdensome on families and NHS resources while enhancing the data that is available for the wider CF research community to use for vital studies.
Clinical Trials Accelerator Platform
The Trials Accelerator is a UK-wide initiative by the Trust that aims to improve participation and increase equity of access to CF clinical trials. The Trust is building a network of CF centres who will lead in the delivery of high-impact CF clinical trials. Each participating centre will be awarded funding for a Trial Coordinator to provide the much-needed added capacity to enable Trials Accelerator centres to increase the number of clinical trial opportunities for their patients.
In addition to supporting CF centres to deliver clinical trials, the Trust is also creating a digital hub of clinical trials. The digital hub will serve as an educational tool to help engage the CF community in clinical trials, clarify common misconceptions surrounding clinical trial involvement and – most importantly – let people know of the opportunities there are to take part in research.
The hub will consist of a number of dedicated clinical trial webpages with an array of online information resources including videos, case studies and FAQs surrounding clinical trial participation.
There will also be a searchable clinical trials database called the ‘CF Trials Tracker’; the first UK CF-dedicated clinical trials database which will list all clinical trials and studies taking place in the UK. This will act as an important tool to help the CF community search for clinical trial opportunities they may be interested in and suitable for.
Research strategy and investments
Our research strategy tackles the aim of a life unlimited at every stage of the journey. At one end, we fund basic research aimed at the genes involved in CF and its symptoms (such as gene editing and small molecule interventions) that feed into Phase 1 trials, through to investment in toxicology first-in-man studies for gene delivery.
Campaigning and lobbying
None of the work we do would be possible without you and not just because of your incredible fundraising feats – your voice is the heart of our campaigns.
Your stories help us understand what you value and where we need to work hardest for you. We work closely with politicians and decision-makers throughout government and the NHS across the UK to deliver our message that we are fighting for a life unlimited for people with cystic fibrosis. Our Stopping the Clock campaign has reached thousands of people and your continued support will help us make real progress in access to new and improved medicines and care.