Kalydeco is a small molecule with big implications. This little blue pill is changing the lives of the 4% of CF patients with the G551D mutation. Trials to see if Kalydeco works for other similar mutations are underway. Phase 2 data released by Vertex on April 18th, in a press release, has bolstered hopes that Kalydeco might work in combination with various other small molecules to treat a much broader range of CF patients including people like me with the most common delta F508 mutation.
This is amazing and really important but there’s a long way to go from Kalydeco to a Kalydeco-like therapy for all 1,800 mutations and it is important to remember that, even for G551Ds, Kalydeco is not a cure. People on Kalydeco still have CF.
For young children whose lungs are not yet damaged by infection, drugs like Kalydeco could be very close to a cure. For older ones whose lungs have been damaged, Kalydeco might freeze the disease but it won’t reverse damage already done. So even if there was a Kalydeco-like treatment for all mutations, symptom-management tools will still be needed. In fact, they may well be needed more than ever because people with CF will be living longer.
CF is a complex disease and it seems inevitable that complex combinations of small molecules and other therapies will be needed even within a common mutation. I think it’s vital for the CF community to nurture some alternative viewpoints and facilitate some alternative science. I think we need to hedge our bets.
Given the lethal mechanisms of CF, there is clearly a point where addressing the symptoms very effectively could be thought of as modifying the disease or changing a patient's life prospects. If a treatment knocks back a chronic infection like Pseudomonas so well that it materially slows down the lethal cycle of infection, inflammation and scarring, it could have a massive impact on quality of life and life expectancy. Materially reducing the frequency of exacerbations will extend life as each one leaves its mark. It is very important that we continue to develop these kinds of therapies.
The CF Trust has always been committed to research and I think this commitment is more important now than ever before. Of course, the Trust established and funded the Gene Therapy Consortium and this is pioneering new techniques that may turn out to be just as important as small molecules or more important. This would not have been possible without the Trust’s funding and sheer determination. I hope the Trust can continue to support this programme as part of a broader portfolio.
I think it’s essential that the CF Trust works in conjunction with the CF Foundation and others to achieve a diversified portfolio of therapeutic options. It is very important to go after more effective symptom-management tools (particularly those which can reduce inflammation or neutralise Pseudomonas and other lethal bugs) and to pursue alternative approaches to rescuing chloride channel function. I hope everyone can work together and I hope it will deliver a more balanced line of attack.
The CF Trust’s research strategy recognises this and I believe it will make a big difference.
One of the most challenging aspects of having CF, for me, is the heavy burden of daily treatment. CF adherence is not just popping pills - it is real work and it is difficult to fit everything into the day. Some of the treatments are unpleasant - they require a lot of effort and willpower. It becomes much harder to get all your treatments done, and it takes longer, when you’re not feeling so well which is, of course, exactly when you need them most. It is easy to feel overwhelmed with treatments. It’s hard to find a balance. It is hard to create reliable windows for work, family and friends; and for all the other things you have to do to get by in life.
So we need to find ways to reduce the burden of treatment by finding faster, more convenient, more portable options, perhaps eliminating treatments that aren’t actually helping, or helping people find practical solutions so they can fit things into their life more easily. Something which saves an hour a day and can be done anywhere is going to have a dramatic impact on quality of life and, I think, adherence. Clearly there is a link between poor adherence and hospitalisation. We do too much fire-fighting and we need to focus more on prevention. We need to recognise the value of prevention.
It may be simplifying treatments; developing a pill or inhaler to replace a nebuliser; perhaps bring in some sports psychology techniques; or a web-based platform or a smartphone app that helps to manage and motivate or allows people to track their progress or even just talk to someone who’s in the same situation (because don’t forget we can’t meet up due to risk of cross-infection). This kind of thing could help people live a fuller life, stay healthier, reduce exacerbations and keep them out of hospital. This is worth doing and I think it’s great that the Trust has highlighted this area and reducing the overall burden of treatment as key research priorities.
In the UK, about 10% of CF patients have participated in a clinical trial. We need to do more. We make it far too difficult for sponsors to do trials. We need to make it easier because we’re all losing out.
Studies show that simply taking part in a trial can improve a patient’s health and that is irrespective of whether they receive the active drug or placebo; and irrespective of whether the trial has a positive or a negative result. It is not just about being an altruistic guinea pig, it’s about direct benefits (for patients, clinicians and hospitals) and a positive culture that forces everyone to raise their game and not to settle.
This means making sure that, when there is a new drug, our patients have the opportunity to take part in clinical trials but it also means doing more trials to make sure we are using the tools we already have as effectively as we can.
Clinical trials, funded by the CF Trust, like the TOPIC study on once vs three times a day aminoglycosides, have resulted in significant improvements in care. In some cases they have allowed treatments to be simplified and ineffective ones to be stopped. These kinds of trials are really important and we need to do more.
It also makes sense to get patients and parents involved in clinical research at the design stage. After all, clinicians only see patients and collect data when the patient comes to the clinic or in hospital. It is the patients and their families who live with CF day-in/day-out. We are the only ones with a 360 degree view. Why can’t we use this experience, and data collected at home, systematically to inform clinical trials and make sure we’re asking the right questions and working towards the outcomes that are most relevant to patients in their daily lives? Internet technology has made this easy to do and, if our aim is to improve real world outcomes, I think we have no choice but to embrace it. That’s why I am really happy about the CF Trust’s commitment today to facilitate patient involvement in this more strategic aspect of clinical trials.
The CF Trust’s research strategy provides a scientific map but, what I think is most important, is the clear signal of the Trust’s intent to collaborate with new partners, in new ways and to make resources available to help people convert their ideas into new therapeutic tools.