What the Vertex Phase III Results Mean

Following yesterday's announcement from Vertex Pharmaceuticals of the results of the Phase III clinical trial of the ivacaftor and lumacaftor combination therapy, our Director of Care & Research Dr Janet Allen explains the key results.

Vertex announced the Phase III

combination clinical trial results for people with cystic fibrosis carrying two copies of F508del (which accounts for around 50% of the UK cystic fibrosis population). Now the dust has settled from the flurry of excitement, I’ve had a chance to look through some of the details in the text beyond the headline data on FEV1 lung function. What I find striking is the effect of the combination treatment on pulmonary exacerbations, which is remarkable, especially alongside such modest effects on FEV1. This finding on pulmonary exacerbations translates through to significant reductions in hospitalisations (39-61%) and IV antibiotics (45-56%). As we all know, pulmonary exacerbations contribute to continuing decline in lung function for people with cystic fibrosis. Together with the need for hospitalisations and IV antibiotics, this has a demoralising effect on individuals and their quality of life. The data here implies that these events could be halved by the combination treatment.  We have just come off the phone with Vertex where we discussed this exciting data and the team commented that many of its expert panel have also remarked on the beneficial effect on pulmonary exacerbations and how disproportionate it is to the effect on FEV1. Clearly more analysis needs to be completed and we need to have a better understanding of this effect but it is remarkable and shows that FEV1 is not necessarily the gold standard marker for measuring the effect of a drug in cystic fibrosis.

The other point that should not be missed is that this is a landmark scientific achievement. The F508del mutation in CFTR causes this protein to be fold incorrectly, which is a really difficult problem to fix. Many other conditions are caused by misfolded proteins and many programmes have tried unsuccessfully to restore the folding pathways in people. Here, a small molecule has been discovered that affects the complex folding of the protein, CFTR. This is an amazing achievement and shows the real value of linking high quality science and drug discovery with the determination to make a difference. 

The Trust is looking for people who took part in the trial to share their experiences – please email James Barrow, Head of Public Affairs, at james.barrow@cysticfibrosis.org.uk.

Extracts from a Short and Merry Life - Part One: Sport & Fitness

Earlier this month, Tim Wotton published his memoir of living with cystic fibrosis, 'How Have I Cheated Death? A Short and Merry Life with Cystic Fibrosis'. In the run up to his book signing event this Saturday 28 June at Waterstones Wimbledon, we'll be publishing three extracts from the book focusing on three themes. The first of which, is the role of sport and exercise:

Without a shadow of a doubt, a large part of my longevity in my battle to defy CF can be credited to the amount of sport I have played throughout my life; mainly hockey, basketball, tennis, rugby, football and cricket.

In my experience, I have found that regular exercise has become a necessity to keep my lungs ‘tuned’ and it impacts me both physically and mentally. I strongly believe that any activity that exercises the lungs of someone with CF is hugely beneficial.

Exercise is not actually straight forward for most CF sufferers as the build-up of mucous in the lungs means that less oxygen is available which causes problems with breathing and general fitness. It is also an extremely exhausting condition – just think how tiring it is to cough for five minutes non-stop. I find it quite literally knocks the wind out of my sails.

For me, still playing sport, running and competing is the best barometer for how my health is. It also serves as an indication for others, not least my dad, to know that if I’m still able to play, that CF can’t be winning the battle. Indeed, my dad will always ask “How’s your wobble son?” and most old friends tend to lead conversations with “Are you still playing hockey?”

At times, I feel the weight of their hope and expectations on my shoulders. What would they think should I ever reply: “Actually, I’ve had to pack it in as it became too much for me!”

I play on for my own health but also for the positive lift it gives to others. I now feel a tremendous sense of elation on completing any sport as it feels like ‘my Everest’ moment. It’s hard and I do have to get pretty psyched up these days before most exercise. It’s still important for me to compete against relatively healthy and fit people as it serves as my health benchmark.

My lungs do definitely benefit from exercise, even small jogs and I feel more vibrant and alive afterwards. I wouldn’t say the exercise is always enjoyable, but the rewards and positive sensation drive me on. It’s only after I’ve pushed myself during a hockey or tennis match that I feel really ‘alive’. I have had to consistently find the motivation to keep going with my hockey. Few 39 year olds I know are still partaking in competitive sport and they all have their reasons not to – it’s easier not to be active once you have a busy work and family life. Some people need a goal to get running again – something to aim for, like a 10K charity run, marathon or triathlon. I have my hockey.

I am desperate to still be playing sport at 40. Fighting CF gives me the encouragement that few can harness. It’s more than feeling that I have to do exercise, it’s lighting my own internal touch paper to force myself to ‘want’ to do it, which creates my own intrinsic motivation. I focus on both the mental and physical aspects of this desire. Physically, I think what’s more of a benefit to me – running (and enduring a short-term discomfort) or not running (and letting the effects of CF build up). Mentally, exercise is my two finger salute to CF, defiantly declaring “I won’t be beaten. I can do this. I will do this. Just watch me!” 
It’s a simple equation for me to keep playing sport. If I exercise and keep as fit as possible, it’s likely that I will stay one step ahead of the grim reaper. In fact, I would go as far as stating that it’s a matter of my life or death.

Tim will be signing copies of his book at Waterstones in Wimbledon from 6:30-8:00pm this Saturday. You can purchase 'How Have I Cheated Death? A Short and Merry Life with Cystic Fibrosis' from Austin Macauley and Amazon, as well as WH Smith, Waterstones and Foyles.

Reflections From Gothenburg

After four action-packed days in Gothenburg at the European Cystic Fibrosis Society annual conference, Ed presents his ‘top ten’ reflections of the last few days:

We are in a new era of cystic fibrosis research

There is belief among the world’s best scientists and clinicians that cystic fibrosis research has entered a period of extraordinary opportunity with the prospect of drugs and therapies focused on correcting the basic genetic defect. As Jerusalem’s Professor Eitan Kerem said in his inspiring speech at the opening session, "Ivacaftor [Kalydeco] provides belief there is light at end of tunnel for cystic fibrosis." The conference showcased a range of other ongoing research, including a drug made from Norwegian seaweed due to be trialled in the UK and elsewhere this year!

But let’s keep our feet on the ground

It is an exciting period but we must ground our expectations in reality. Even if the results of the Phase 2b gene therapy trial, expected in October, are positive, there is a long way to go before it can be assessed for wider clinical impact. And no one expects the data from Vertex’s Phase 3 trial of a combination therapy of Kalydeco and lumacaftor (VX809) for those with two copies of the D508F gene, due to be published in a few weeks’ time, to be as dramatic as Kalydeco for those with G551D. There is much to be done, but this conference has reaffirmed my belief that we are making significant progress towards our goal of beating cystic fibrosis for good.

Don’t forget the simple things

While much of the attention of the cystic fibrosis community is on this transformational research, there is much more we can achieve by helping to prevent and manage the symptoms of cystic fibrosis. A very good session I attended talked about the importance of exercise for all people with cystic fibrosis. The US’s Anne Swisher said that kids and teenagers with cystic fibrosis should be aiming to do at least one hour of moderate to vigorous activity a day, while adults should aim for 150 to 300 minutes a week. Sweden's Margareta Sahlberg urged parents to start their children doing regular physical exercise as soon as possible – and always with a smile!

We have fantastic health professionals in the UK

Seeing British clinicians and health professionals like Stuart Elborn, Di Bilton, Jane Davies and Tim Lee leading discussions and debate on the major issues at the conference this week, and the esteem in which they are held across the world, reminds me how lucky we are to have such a group of committed and dedicated professionals working to improve and transform the health of people with cystic fibrosis.

But those with cystic fibrosis and their carers are experts too

Those living with cystic fibrosis every day have extraordinary knowledge – and the NHS needs to do more to ensure people are shaping the way their care is provided. Dutch psychologist Yvonne Prins, who also has cystic fibrosis, gave a thought-provoking talk about creating “person-centred” care to put the needs, wellbeing and interests of those with the condition centre-stage rather than as merely recipients of clinical treatment. She suggested that clinicians and health professionals needed to ask themselves if, when they saw someone with cystic fibrosis in clinic, they saw a patient, a pair of genes or a person. Only if it was the latter could they begin to properly help develop a form of care that understands the emotional complexity of living with this lifelong condition.

We can be proud of what the Cystic Fibrosis Trust is doing

The Trust needs to constantly improve what it does to ensure it has the maximum impact on those we are here for. It was heartening to speak to a range of cystic fibrosis organisations from across Europe that want to learn from what we are doing, particularly on research and clinical care. The UK CF Registry is a great example, and the work to use the registry in partnership with companies like Vertex and Pharmaxis to help study the safety of new drugs being introduced in UK clinics got a great deal of interest at the conference.

But there is much more we can do

I was able to use the conference to meet a number of companies who we might work with to help develop new research opportunities for people with cystic fibrosis.  The Cystic Fibrosis Foundation in the US – who we are working with on a number of fronts - has led the way in this regard, and there is more we can do. It was good to see Novabiotics represented in Gothenburg. They are a UK-based bio-tech company we are now in partnership with to trial a drug to treat lung inflammation, and I want to see more of this as we deliver our research strategy.

We need to co-operate and collaborate to achieve more

These conferences help build and cement important relationships. There is a great deal that the Trust can do alone, but there is so much more we can do working with others – whether cystic fibrosis charities or companies and other groups. If we can use our expertise and resources to leverage additional funds and know-how into cystic fibrosis then we will. So expect more cooperation at a European level to access vital EU funds to research key areas of cystic fibrosis, and help ensure more clinical trials can take place when needed.

The voice and experience of those with cystic fibrosis can change the world

We must never forget that for all the extraordinary expertise within the clinical and scientific world, it is often the voice and stories of those with cystic fibrosis that make the difference. That was what made the difference on ensuring Kalydeco was made available to all eligible across the UK, as well as Manitol, Colobreathe and other new therapies. It will be so again when other drugs appear – and as we work to shape a healthcare system that puts the interests of people with cystic fibrosis first.

Let’s look forward to next year

A lot will happen in the 12 months before the next ECFS conference. We will be working very hard to make a significant contribution to the change occurring in cystic fibrosis and to improve our work for people here in the UK. With the tremendous support of the wider cystic fibrosis community, I am confident we can achieve a great deal. I am also relieved that the next conference is in Brussels which is much easier to get to!

A First Time View of ECFS Conference

Today's blog from ECFS Conference comes from James Barrow, our Head of Public Affairs, who is first time attendee to the event

It is my first time at the European Cystic Fibrosis Society (ECFS) annual conference. The atmosphere is friendly and optimistic with a strong sense of community.

Yesterday I attended the Opening Ceremony led by Johan Mostrom, Chairman of the Cystic Fibrosis Association of Sweden. As part of it Ulrica Sterky - a parent and Chairperson of the Local Liaison Committee, gave a personal account of her family’s journey with cystic fibrosis since the birth of her son in 1982. She highlighted the positive changes during his lifetime and reminded delegates of the importance of putting people with cystic fibrosis at the heart of research.

I then met Orla Tinsley, a journalist and author who has successfully campaigned for the rights of cystic fibrosis patients in the Republic of Ireland. It was fascinating to hear how the power of personal stories made cystic fibrosis a national issue in Ireland and improved standards of care. Very inspiring.

This morning I met with Vertex Pharmaceuticals to discuss the drug pipeline followed by sessions on ‘New Psychological Approaches and Transplantation - Challenges and Hopes’. 

Psychologists from across the globe discussed the need for a holistic approach to psychotherapy and evidence to support the effectiveness of e-help and group methods. 

During the transplantation session EU statistics showed that the UK has the highest survival rates post-lung transplantation but the second longest waiting time pre-transplantation. I was interested to learn that Germany recently introduced a lung allocation system, similar to the one we are campaigning for, which reduced waiting list mortality from 22% to 14%.

Next is our meeting - the UK Cystic Fibrosis Trust. A great opportunity to talk about the work we are doing. Then onto a workshop about ‘Screening and Diagnosis’.

Setting the scene for ECFS

As the first day of ECFS Conference draws to a close, Ed Owen, Cystic Fibrosis Trust Chief Executive, sets the scene for what the next four days will mean for the cystic fibrosis community across Europe and beyond.

I arrived in Gothenburg, Sweden’s second city, yesterday evening to take part in the annual European Cystic Fibrosis Society conference.

It is an extraordinary event that runs for four days with clinicians, scientists and bio-pharma companies from across Europe and elsewhere congregating to discuss crucial issues relating to cystic fibrosis research and care.

And it is a vital opportunity for me and colleagues to build relationships with key people and organisations to assist the Trust’s work to improve and transform the lives of people with cystic fibrosis in the UK.

So last night I caught up with my equivalent in the German cystic fibrosis charity, Andreas Reimann, to discuss how we can work together in Europe to boost the number of clinical trials to accelerate the development of new therapies and treatments. Today I am meeting other associations, and key clinicians who operate as part of the European Clinical Trials Network.

Alongside this and the many seminars and workshops that are held at the conference I also have meetings booked over the next few days with a series of pharmaceutical companies to discuss cooperation in key areas of research – and we also have a meeting with the many UK-based clinicians here this week to discuss how we make sure the relationship between the Trust and health professionals is working effectively for the good of all people with cystic fibrosis.

Some weeks ago there was talk that this conference might be the occasion when Vertex revealed the data from its Phase 3 trial of its combination therapy of VX-809 (lumacaftor) and Kalydeco (ivacaftor) for those with two copies of the D508F gene. Unfortunately we are going to have to wait a few more weeks for that, as the company’s CEO, Joe Leiden, told me when he was in London last week.

But, as with all cystic fibrosis conferences being held at this time, there is a collective sense of cautious optimism among all those here with new therapies and treatments offering the potential to have a fundamental impact on those with the condition, and better understanding to further improve the way the symptoms of cystic fibrosis are treated.

We are determined to ensure the Trust plays its part in making this happen. This week will contribute to helping us do so.

Gearing up for ECFS

Four members of staff from the Cystic Fibrosis Trust have travelled to Sweden in order to attend the European Cystic Fibrosis Society's annual conference, to meet,engage and collaborate with colleagues from across the continent in the fight to beat cystic fibrosis for good. Over the coming days we will be bringing you updates from those there. Starting us off is Dr Janet Allen, Director of Research & Care.

It’s June so that means it is ECFS – the major European meeting for cystic fibrosis. The conference, which this year takes place in Gothenburg, Sweden, starts properly tomorrow with an opening plenary session. The following days are packed with sessions from first thing in the morning through to the evening, until Saturday afternoon.

I arrived a day early to represent the Cystic Fibrosis Trust on behalf of Ed Owen at a strategic meeting of all the cystic fibrosis organisations across Europe. ECFS is an excellent opportunity to meet colleagues from these organisation to see how we can work better together and maximise the opportunity to secure European funds to benefit cystic fibrosis research. The EU research programmes are run on a seven-year cycle and last year, the EU published its blueprint research strategy 2014-2020. This time, the EU has been a bit more adventurous in its title and instead of being called ‘Framework 8’, this strategy is titled ’Horizon 2020‘, which perhaps reflects a more aspirational view for research. It is important that we work together to improve the chances of securing part of the EU research budget, which , although enormous, covers all aspects of science and medicine. It was good to hear of the plans of the other cystic fibrosis organisations and see the opportunities for a combined assault on Brussels. It was also great to have an update on the European Clinical Trials Network. This network links large cystic fibrosis centres in five countries in Europe – sharing knowledge and experience to review trial protocols to try to troubleshoot before the trial starts recruiting.

To Petra and Back Again

25 February - 2 March saw 21 intrepid adventurers, including TV's own Sian Lloyd, take on the desert of Jordan in support of the Cystic Fibrosis Trust. We asked Sam Davies, Events Manger for the Trust who was part of the trek to give us a round up of the experience, our first overseas challenge.

Our five-day Petra Trek was a great success. All 19 of our trekkers managed the 27.5km route, including some very steep climbs, thin cliff-top paths hundreds of feet up, and hot desert tracks.

The group soon bonded, helping each other to overcome personal and group challenges, while enjoying spectacular scenery, fascinating history, and the beauty of the ‘lost city’ of Petra.

Our local guides gave us a fascinating insight into ancient and modern Jordanian culture, and we were lucky to experience live Bedouin music around our campfires, while sitting under an incredible desert night sky.

We are on track for raising £50,000 from the event thanks to everyone who has sponsored our trekkers, and are very excited about upcoming overseas challenge events later this year and next.

You can see more about what happened on the Petra Trek over on Storify, where we've collated people's tweets and photos.

Inspired? Then sign up for one of our next adventures