Saturday, 10 September 2016

CTAP - what's the big deal?

Earlier this week the Cystic Fibrosis Trust announced its Clinical Trials Acceleration Platform (CTAP), a new initiative to increase capacity for CF clinical research in the UK and make it easier for people with CF to find out about and take part in research if they choose to do so.
This is an initiative I have been working on with the CF Trust for the last 3 years because I believe passionately that the current system for doing CF clinical research in the UK is inadequate (and not really a system at all) and that people with CF deserve better. Many people living with CF, CF consultants and others who do research agree and want to help build a better system. 

I am very excited to see CTAP moving forward but it won’t work unless the whole UK CF community comes together to make it work. I hope you all take a moment to find out about CTAP and think about what you might be able to do to help make it a reality for the benefit of those of who live with CF today and future generations.

As we know, research is needed to evaluate the safety and efficacy of new medicines, to compare existing treatment options to make sure we are using them as effectively as possible and to improve the quality of clinical care. Getting involved in research is also a clear statement that we will not settle for the status quo.

Taking part in clinical research, either as a participant in a specific clinical trial or by giving input into the design and running of better quality, more relevant, more user-friendly clinical trials through Patient & Public Involvement (PPI), is something we can all do to really make a difference. 

Today clinical trials are only generally available to those people with CF who happen to be at certain centres. These tend to be the larger CF centres but everyone with CF deserves the option of taking part in clinical trials and we should all have easy access to the information we need to make informed decisions about participating.

This is why the need for action is URGENT:

·         Despite huge advances over the last 50 years, people with CF are still dying far too young;
·     The lives of people with CF and their families are still severely impacted by the disease and the burden of treatment;
·         We are reaching a critical juncture with numerous new therapies requiring evaluation;
·         A bottleneck is emerging where the US clinical trials network and large CF centres in the UK are having to turn new trials away because they are already saturated and have no spare capacity;
·         We do have the European Clinical Trial Network and 7 of our UK CF centres are members of that but, despite a clear collective interest, there is no coherent system for CF clinical research in the UK. We have lots of CF centres, other groups, individual researchers and others doing great things but they are largely doing their own thing. There is no central co-ordination or management. This results in inefficiency and an overall situation in which resources are wasted despite the best intentions of the very dedicated and talented individuals who are involved in CF research in the UK;
·         Global interest in CF research is currently high as a result of Ivacaftor showing: a) that it is actually possible to restore CFTR function; and b) that when CFTR function is restored, the health of people with CF improves in a way that significantly improves health outcomes and actually makes people feel better;
·         While this level of Pharma interest exists, it is essential that we organise ourselves as a community to make the most of the pipeline and translate it into maximum benefit for people living with CF. If we don't do it, Pharma interest will fade away and the pipeline will collapse under its own weight.
CTAP seeks to address all these things and create a system for UK CF research which can help relieve the global bottleneck, push new drugs through the pipeline and give people living with CF in the UK a better chance to access them.

At the moment, only about 1 in 10 people with CF in the UK has taken part in a clinical study or trial. Only 55 patients in the UK (out of 1,100 globally) took part in the Phase 3 trials for Orkambi. Based on the number of people with CF in the UK, you would expect at least twice as many UK patients to be in the trials like this. If we can go from 10% of people with CF taking part in studies/trials to 20%, it will have a very significant impact.   

I also believe that a more effective system for CF clinical trials will help to reduce drug development timelines and boost competition which will reduce Pharma’s pricing power and make it easier for us to access new therapies in the clinic.    

While new treatments are exciting it is also really important to make sure we understand the evidence for existing therapies and optimal combinations of therapies (such as IV antibiotics) and know that we are using them as effectively as we possibly can. If we don’t do this, we will be accepting that people with CF will suffer unnecessarily and we will not be in a position to capitalise on new therapies, which will only work properly when there is a strong foundation in terms of the standard of care. Luckily, CTAP is looking to help make these kinds of studies easier too.

It is really important that people living with CF help to shape and manage CTAP to make sure it fulfils its potential. Please register your interest by clicking on the links below. As CTAP takes shape, you will also be able to help by volunteering for specific clinical studies/trials, getting involved in PPI and just talking to your CF team about opportunities to take part in clinical research. Don't wait to be asked. If your CF centre does not do research, please ask them why.  

Here are two really important PPI roles to consider applying for:

PPI Coordinator (closes 12th Sept 2016): CTAP PPI Coordinator Role
PPI Advisor (closes 30th Sept 2016): CTAP PPI Advisor Role 

Here is some more information on CTAP: Announcement of CTAP

Here is where you can register your interest in being informed of developments and potentially getting involved in the future: Register your interest

Please check it all out and get involved if you can.

Monday, 2 November 2015

Drugs, Mucus and Money

Cystic fibrosis (“CF”) causes thick, sticky mucus to build up in the airways and people with CF work very hard each day to clear the mucus from their airways using a variety of inhaled medications and physiotherapy techniques. None of these treatments fixes the problem they just buy you time and space for bits of life.

CF mucus is sticky stuff, hard to shift. It doesn't come up by itself, it's not like saliva, more like glue, it grips whatever it touches, it can take several flushes to get it down the toilet. It is nasty stuff, you think to yourself “surely this must have industrial applications or maybe it could be used as a form of renewable energy/biomass. Perhaps I could sell it!”, then crackles and gurgles in your airways demand an end to the day dream and it’s back to work, it's like wrestling with a sticky bear. This work takes energy, patience and skill (deliberate breathing, huffing, coughing techniques), it soaks up energy, it causes headache and nausea (especially if you have the signature CF bloated stomach. You have to be tuned in, listening/feeling for sounds (crackles, wheezes) vibrations to give you clues and direct your efforts, you have to proactively hydrate your airways “from above” with inhaled therapies like hypertonic saline and “from below” by drinking lots of water, just to give yourself a chance. 

This is never ending, your work is never finished - there is always more gunk down there, crackling away and trying to sop you breathing. So when you stop for a rest you feel like you should be doing more and you start to feel guilty. It can feel pointless - like Sisyphus trying to push the rock up the hill. 

You can’t meet others with CF because there is a real risk of cross-infection so you have to get on with it by yourself. You used to be able to meet others with CF because nobody knew about the risks then but it is different now and most of them have passed away now anyway. It can be a lonely battle. Hours of treatments and clearing 50-100 ml of mucus each day, even when well, with no chance of a day off, can be gruelling. It can feel like a cruel form of punishment.

If mucus is crackling and gurgling away in your airways, it is impossible to sleep. So even though you are exhausted you can't sleep. You have to do more work just to try to clear a bit so you can have a chance of a little sleep. But as you sleep, it builds up again because you are not clearing! And after a while you're too exhausted to do all your treatments, or eat but if you don't do that you will get worse. You are exhausted to work but you get no real help from the government because you can walk 50m and “look healthy” so then you have no money to support yourself or buy food or pay the rent or get to the hospital. This is normal life, it is worse when you are unwell. It is like this everyday, 7 days a week, 365 days a year.

Eventually you will drown in your own mucus unless you get a lung transplant. And you know this from the start. And there is nothing you can do to prevent it, you can only delay it. Unless someone develops a cure.

And then a company called Vertex comes along with a pill which is not a cure but which looks like it might actually start to address the underlying problem (like 10% of a cure) but they want $300,000 per patient per year for this pill and there is no way you will get it because the money is not there to pay for it. And the company says if they don't charge such a high price, they won't be able to afford to do more research to finish the job. But nobody really knows how much it costs to develop these pills. It's a secret. We all know it is risky business and most drugs fail; and that the winners have to pay for the losers. It’s like you can't point at a lottery winner and say they shouldn't get the jackpot because they only paid $1 for the ticket! Obviously you have to think about all the losing tickets too. Understood. But that shouldn’t mean they can charge whatever they like. They say they it costs the same to develop a drug for 1,000 people as it does to develop a drug for 1 million people. So in a rare disease like CF they have to charge more per patient to recover this big inflexible, mysterious lump of cost. They say the price also reflects the "transformational" effects for patients (i.e. how much like a cure it is). But then they charge basically the same for a drug which is like 10% of a cure with a market of 30,000 people as the earlier one they made for 2,000 people which is like 40% of a cure for those people. So the logic doesn't hold. And the executives who work for the company who are not the people who did the science and developed the pill) get paid tens or even hundreds of millions of dollars a year in salary, bonus and equity and this tells us the company has a lot of excess money so it makes even less sense. It just looks like they are charging what they can get away with. Because there aren't very many people with CF and we have no political clout, nobody with power cares and nothing changes. Then the mucus starts gurgling away and it's back to reality, time to try to clear it out again. Because you like being alive and that means you need to be able to breathe.


Friday, 3 July 2015

Phase 2b Gene Therapy Results

Today the results of the UK CF Gene Therapy Consortium’s Phase 2b clinical trial were published in Lancet Respiratory Medicine. The trial achieved its primary endpoint by showing gene therapy improves FEV1 in a statistically significant way. It is a big step forward for CF science.

·         The CF gene is essentially an instruction to cells to produce a certain protein (CFTR) that is needed to allow salt and water to pass across cell membranes. Without this protein, airways and other important tubes get clogged with sticky mucus that a) obstructs the tubes; and b) acts as a breeding ground for bugs. Researchers are trying to find CF therapies to address the underlying defect at both the gene and the protein level. There is also an intermediate step where the CF gene produces a copy of itself (called RNA) and that copy is used by the cell to manufacture the CFTR protein. Researchers are looking to design therapies that work at the RNA-level too (e.g. ProQR).  

·         CFTR modulators like Ivacaftor are thought to work by attaching to the defective CFTR protein and encouraging it to work properly. They do not do anything at a genetic level. Since different CF mutations mean different defects in the CFTR protein, CFTR modulators are developed for specific mutations. This is one reason why they are extremely high priced. Gene therapy works by putting a working copy of the CFTR gene into cells so that the cells themselves produce normal CFTR protein (just like someone who does not have CF) so the individual CF mutation is irrelevant. This should also make the therapy more cost effective.

·         It is hard to get the gene therapy into the airways where it can actually work because the lungs have evolved very effective self-defence mechanisms. Getting gene therapy into the lungs means penetrating these natural defences as well as getting through all the mucus that clogs the airways of people with CF. This needs to be done without triggering an immune response that creates problems which outweigh any benefit of the therapy. So the key challenges are delivery and safety.

·         While gene therapy is not yet a finished product and patients on the Phase 2b trial probably did not feel major improvements in themselves, the results show that gene therapy can safely deliver statistically significant treatment effects. Scientists think the efficacy can be improved by increasing the dose/frequency of administration and tweaking the vector (i.e. the design of the “missile” that delivers the gene therapy “payload”). It is an important stepping stone in the development of gene-based therapies that seek to correct the underlying defect and achieve a functional cure for all CF mutations.

·         The 3.7% difference in mean relative % predicted FEV1 in the gene therapy group compared to placebo is only slightly lower than that seen in the Phase 3 trials of Lumacaftor/Ivacaftor in homozygous F508dels (4.3-6.7%).

·         There were no safety issues.

·         The gene therapy essentially stabilised lung function – the 3.7% difference was driven by deterioration in the placebo group.

·         There was a wide variation in response. The gene therapy benefited some much more than others and it is not clear why.

·         A wide range of mutations were included in the trial and treatment effects were independent of mutation.

·         Those with more severe disease (less than 70% FEV1) saw bigger effects but it is not clear why this is. Intuitively, it makes sense that greater mucus obstruction in the smaller airways of those with more sever disease would mean more drug dwelling in the larger airways with a greater opportunity to act. It may also be harder to show benefit in patients who are already relatively well.

·         This trial has shown repeat doses of gene therapy can be delivered into the lungs in a way that is safe and produces benefits in terms of key health markers. Hopefully it will give researchers and funders confidence to build on this work and explore the potential to tweak the dose and/or the frequency of administration; develop superior vectors; and also find an efficient way to test gene therapy in combination with CFTR modulators like Ivacaftor.

·         Further out, the data should have positive implications for future iterations of gene therapy, RNA-based therapies and gene editing approaches; and the UK GTC’s data, know-how and experience is a community asset that will inform work in all these areas.

·         It is an exciting time in CF because Ivacaftor has shown that, in certain mutations, the functionality of the CFTR protein can be rescued and that, when this is done, people with CF get a lot better. It has shown us what the destination looks like. However, the recent results from Vertex’s Phase 3 trials of Lumacaftor and Ivacaftor in combination for people with two copies of DF508del, the most common mutation, show there is a long way to go before people with that mutation and other rarer ones have a CFTR modulator therapy that does for them what Ivacaftor monotherapy does for G551Ds. Even if they work, we may not be able to afford them. 

·         While Ivacaftor for G551Ds has set expectations sky high, in reality for most people alive today with CF, stabilisation would be a very successful outcome. Stabilisation, if maintained over a number of years (as compared to the standard annual 2-3% decline), could mean that a person with CF takes, say, 60 years to get to the point where they need a transplant rather than, say, 40 years and that is a big deal – it could mean a very different kind of life for them and those around them.

·         For mutations which are not responsive to Ivacaftor monotherapy, it is unlikely that a single pill or other form of treatment will have all the answers. It is likely we will need combinations of different forms of therapies (gene-based, RNA-based and protein-based) working together and some form of gene therapy could be a component of the overall solution.

·         This trial and the openness in relation to the data is a huge credit to the UK CF community and it makes me proud to be part of it. While the Phase 2b trial itself was funded by MRC/NIHR, a huge amount of work has taken place over the last 15 years to get to this point and 90% of the overall funding has come directly from the UK CF community. Indeed, it was the Cystic Fibrosis Trust that put the UK Gene Therapy Consortium together in the first place. Adults with CF and parents of children with CF have made this happen.

·         It has cost around £45m to get to this point. This is much less than the figures usually sited by industry for getting through Phase 2.

·         Patients from 18 UK hospitals were able to take part in the trial. Not many hospitals have the facilities or the capability to do trials like this but allowing local hospitals (acting as “Patient Identification Centres”) to refer willing and eligible patients to one of the two participating centres meant the trial could recruit to target and it extended the opportunity to participate to a much wider group of patients. There is going to be an increasing bottleneck in CF drug development as the big CF centres are unable to cope with all the trials that will need to be done to convert the pipeline and exciting science behind it into therapies for patients. There is also an issue of equality of access to trials - it is not fair that only patients at the big CF centres should have the opportunity to take part in clinical trials. The Patient Identification Centre model, used for the first time in the Phase 2b gene therapy trial, may be a way to address some of these important issues. 

Wednesday, 25 June 2014

Vertex results from TRAFFIC/TRANSPORT

Yesterday Vertex announced preliminary results from the Phase 3 trial of Lumacaftor in combination with Ivacaftor in patients aged 12 and over with two copies of the F508del mutation. The trial involved 1,100 patients at almost 200 sites across the world.

For me, the most interesting points were:
  • Mean absolute change in % predicted FEV1 was approx. 3% and mean relative change in % predicted FEV1 was approx. 5% (on the basis of pooled data). That means if a patient’s baseline FEV1 was 60%, on average they would have seen an increase to 63%. While this is less dramatic than the effect seen in G551Ds on Ivacaftor monotherapy, it was statistically significant and, for many people with CF, each % point maintained is important;
  • Statistically significant increase in Body Mass Index (BMI)
  • Delayed time to first pulmonary exacerbation;
  • 30-39% reduction in pulmonary exacerbations (depending on the dose);
  • 39-61% reduction in exacerbations requiring hospitalisation;
  • 45-56% reduction in exacerbations requiring intravenous antibiotics;
  • Some people on the trial had baseline FEV1 below 40%. While the eligibility criteria was 40%, some dipped below this threshold in the period between screening and first drug. These patients seem to have responded just as well as those with higher baseline FEV1;
  • Approx. 90% of people on the trial decided to rollover into the open label extension including those who had been taking placebo during the trial period. This says something about how the drug made patients feel in themselves; and
  • The Quality of Life questionnaire (which is validated by regulators) failed to show any improvement in quality of life. This seems at odds with the data above and, to me, suggests the instrument is not tuned into the things that really matter to patients. Perhaps there is a need to develop a new way of measuring quality of life. It would be a long process to get a new instrument validated but it could pay dividends and it something that could be done in partnership with patients and families.

Vertex now plans to submit the data by the end of 2014 to regulators in the US and EU in order to get a marketing authorisation. If approval is given, they will then embark on the process of securing reimbursement. All this will take time and there are risks at every stage.

While this combination therapy does not appear to be transformational for those with two copies of F508del in the way Ivacaftor has been shown to be in many G551Ds, it is exciting and provides a solid stepping stone for further development by Vertex and others. It is probably more of a bridge to the future than a home run in itself. It should reassure researchers that this problem is one that can be solved.

It is surprising that the effect on exacerbations was so dramatic given the modest effect on FEV1.

Here’s why I think reducing exacerbations is more important than increasing FEV1:

FEV1 is hard to measure in a reliable way even in adults. It is dependent on technique and it can be affected by lots of factors unrelated to underlying lung function. It becomes less reliable as lung function deteriorates which is, arguably, when we most need a reliable measure.

If you ask someone with CF how they feel, they are unlikely to talk about FEV1. FEV1 is not something patients feel or necessarily perceive.

It is well established that more exacerbations lead to worse health outcomes. The mechanism is clear and cruel - most people with CF die of lung failure, every exacerbation can cause incremental lung damage that is irreversible so moving us a little step closer to lung failure. If we think of it like a staircase down to lung failure, we obviously want the distance between each step to be as long as possible and we want each step to be as shallow as possible. Weight gain directly helps here too. Just breathing and keeping permanently resident bugs at bay takes a lot of energy for us. The more energy we have in reserve the better able we are to fight off infections before they flare-up into exacerbations (or the better we are able to minimise the severity of the exacerbations that do hit us). Therefore, weight gain can help extend the distance between steps and minimise the depth of the steps by creating resilience. 

Obviously exacerbations are disruptive to life so there is a clear and immediate quality of life impact for patients and families.

Personally, I wish I had known when I was younger that exacerbations tend to cause irreversible lung damage and knock you down a step. When I was a teenager and relatively healthy, I hated doing all my treatments particularly nebulisers and airway clearance. I sometimes used to think, “I’m fine and busy with my life. I won’t bother doing all my treatments. I'll wait until I get sick and then go to the hospital to get fixed". I didn’t think I was losing anything but I really was.

Traditionally FEV1 is seen as the gold standard test for measuring the effects of new therapies. There may well be a case to review that now. The therapeutic pipeline for people with CF is stronger than ever before and these results will help underpin further development.

Monday, 10 March 2014

Travel Insurance and Oxygen

I have spent many hours researching travel insurance and travel oxygen. I just spoke to Insurance Choice and it feels like a breakthrough. 

They are an arranger not an underwriter. She said the best underwriter by far for CF is "Fit for Travel". They are the only company who write their own medical questions and this makes them more flexible. She took my details and then went through their process with me. The questions were thorough but more sensible than normal. It seemed like they understand CF more than others! 

They have a website but there's not much on it so I recommend just calling.

Tel: 0844 5577980 (ask for Sophie)

I have found in the past that the number of "unplanned" admissions I have had in the last year or two years has been a blocker. I usually go in 2 or 3 times a year. I go in when I am sick not a pre-planned basis. These guys ask about all admissions in the last two years (not just unplanned ones i.e. pre-emptive pre-planned ones count). In the last 2 years I have been in 5 times. This was not a blocker.

I also have CFRD and I need oxygen on the plane, with exercise and overnight. This was not a blocker.

I am thinking about going to Greece for 2 weeks in April. They quoted me £225. She said it would be similar anywhere in the EU.This includes £5,000 cancellation cover and £10m emergency including repatriation and legal.

After getting the quote, I had a decent chat with her. She said the question about admissions in the last two years has two answers "0-9" or "more than 9" i.e. if I had been in 9 times it would not make that much difference. If more than 9 admissions, they may still cover but it will cost more. She said she recently arranged cover for a lady with CF in a similar situation to me who is going to the US. The quote for her was £650.  

I need to take oxygen abroad. I use 2 litres/min pulsed when I do exercise and I use 2 litres/min continous overnight. I will use 2 litres/min on the plan since the flight will be more than 2 hours. I tend not to need O2 for shorter flights. Air Liquide provide my O2 at home and they are pretty good about travel within the UK but they will not help abroad. If you have an EHIC you can arrange O2 locally within the EU but it can take a long time to organise, there is sometimes a cost and I'm told the equipment is not always as good as it is here. I called British Lung Foundation and they gave me a list of companies that will rent out portable O2 equipment to take abroad. This is going to cost me about about £400 for 2 weeks. I tried PureO2 (08707 120202), 10sMedical (0121 355 6555) and Intermedical (0800 0282194) and they are all similar but I would recommend PureO2 because they seem a little bit more professional and responsive. I can use this equipment on the plane too but if I go with an airline that provides it free I might use that facility.

The British Lung Foundation website is good for general information and the people on the helpline are very helpful:

There is also some good inforamtion and advice on the Cystic Fibrosis Trust website:

I hope it is useful for others with CF. Where there's a will there's a way! 

Monday, 26 August 2013

Which CFTR mutations actually cause CF?

A recent study sheds new light on which of the 1,900 plus known mutations of the CFTR gene actually cause cystic fibrosis (CF) and which do not. The study is called "Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene" and it was published on 25 August 2013 in Nature Genetics. The results have important implications for family planning and drug development although this work is ongoing and part of a bigger project aiming to characterize all known CFTR mutations. Researchers analysed genetic information from nearly 40,000 CF patients to find out which of the 1,900 mutations cause CF and which are benign. Their findings increased the number of known CF-causing mutations from 22 to 127. Prior to this, more than 25% of couples in which both partners were found to carry a mutation on the CFTR gene could have no way of telling whether their mutations could actually cause CF in their offspring. As a result of this study, that is reduced to 9%. The work provides some interesting clues for drug development too. By looking at the differences in severity of disease caused by changes in CFTR associated with different genotypes, the researchers have a better idea of the potential efficacy of drugs which achieve the same changes in CFTR.

I emailed some questions to Dr. Patrick Sosnay, co-author of the study and assistant professor of pulmonary and critical care at Johns Hopkins University. 

How did you do this study?

"We collected CF patients and parents from around the world (mostly N. America and Europe) and looked at the mutations they had. We then looked at each of these mutations to tell for sure if they caused CF. We looked at the clinical outcomes of patients that had those mutations (assuming the higher their sweat chloride, the more likely the mutation was truly a CF causing mutation); we looked at how the mutation behaved in experiments (the less it behaved like the non-mutated or "wild-type" CFTR, the more likely it was truly a CF causing mutation), and we looked at how often it was seen in people with CF, vs. carriers, vs. the general population."

What is the relevance of the results?

"We have better defined the range that can be seen with the 159 most seen CF mutations. Some always cause CF, some cause CF some of the time, and some we do not think cause CF. Obviously, because it is a recessive disease a patient has to have mutations on both copies of CFTR they inherit."

What are the implications of this data for family planning?

"This will help genetic counselling in that we will have a better idea what the most likely consequence of a mutation is. People having genetic testing done before this study were more likely to get back a CF mutation that we did not know how to interpret. They would be told – you have a mutation in CFTR, we do not know if it causes CF or not. There are still many mutations out there that are uncharacterized, but we have chipped away at some of the more common ones."

What are the implications of this data for drug development?

"This information will be used by scientists studying therapies to group mutations according to their functional consequences. We also hope to learn more about what contribution CFTR genotype makes to making CF mild or severe."

Is this project continuing and what is the ultimate goal?

"This work is continuing. For every mutation that has ever been seen in CFTR, we want to be able to say: does it cause CF, if so what drugs could be used against it?"

Here is a link to the study in Nature GeneticsDefining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene

Monday, 29 April 2013

Speech to CF Trust Scientific Conference 2013

29 April 2013 at The Wellcome Trust, London.

"Good evening, everyone. It’s an honour to be able to speak to you tonight. It’s a bit overwhelming actually. I feel a bit like a kid speaking to a room full of Father Christmases.

I want you all to imagine – you can close your eyes if you like - I want each of you to imagine you’re in a little wooden boat floating in the middle of the ocean. As you bob up and down, you feel the sun on your back, you can hear the distant sound of birds and you can smell the sea air. Sounds pretty nice. But there’s a problem. The boat is full of holes and water is gushing in. There are sharks. All you have (to bale out the water) is a tea spoon. You spend most of your time baling with your tea spoon trying to stay afloat. You do it all day. You go to sleep, you wake up in a boat full of water and you start baling again. It is exhausting and relentless. You need a bigger spoon. Better yet, you need to find a way to plug the holes. That’s what CF feels like to me.  It’s a fight against drowning in my own mucus.

I was diagnosed in 1978 at the age of 3. When I was 14 my consultant told me I’d probably need a heart and lung transplant in my early twenties and that I’d be lucky to live beyond 25. This [Spoon 1] was standard of care in those days. Well my heart and lungs are still original and I’m still here at 37. During that time, we’ve seen the development of better spoons - nebulised antibiotics like TOBI [Spoon 2], mucus busting therapies like Pulmozyme and Hypertonic Saline; and more effective airway clearance techniques [Spoon 3]. These all resulted from research and I might not be here without them. I want this [Spoon 4] but I have this [Spoon 3]. Kalydeco is a bit different – it’s plugging holes - but I’ll come on to that.

New treatments are exciting and important but, actually, I think it’s just as important to develop better tools to manage symptoms and figure out how to use the tools we already have in a more effective way. 

So I want to talk about three things: the therapeutic portfolio, clinical trials and adherence.


Vertex’s new drug Kalydeco is a small molecule with big implications. This little blue pill is changing the lives of the 4% of CF patients with the G55-1D 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 incredible – when I read the blogs and hear the stories of people on Kalydeco – it is mind-blowing. It brings a tear to my eye. 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 G55-1Ds, Kalydeco is not a cure. These people still have CF.

They still need to do all their other treatments. They still have chronic infections and exacerbations that mean they need IVs - but not as often. They are significantly better, able to do more stuff without getting breathless, put on proper weight, bounce back faster from exacerbations and generally far more resilient. Those on Kalydeco seem able to shake off a cold without it turning into an exacerbation – in other words two weeks in hospital becomes 2 days off work. I hear about patients with G55-1D who’ve come off the transplant list or who no longer need a wheelchair or oxygen therapy. They can go back to work or perhaps go on holiday. Maybe their parents no longer need to act as such full-time carers so they can go back to work or have a more normal life too. These patients are able to think about and plan for the future in an entirely new way. The trajectory of their disease has changed. It is hard to explain because the way CF affects patients and families is so complex - and maybe we need to find better ways of articulating the true value of these medicines - but this is a profound leap forward and it is exciting to think the same approach may help those with other mutations.

For young children whose lungs and other organs are not yet damaged, drugs like Kalydeco could be very close to a cure. For older ones whose organs 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 likely that complex combinations of small molecules and other kinds of therapies will be needed. Lots of money is going into small molecule CFTR modulators. As a patient, I worry we are putting all our eggs in one basket. It may not work. It may half work. I think it’s vital for the CF community to nurture some alternative approaches and facilitate some alternative science. I think we need to hedge our bets.

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. While even this is not a “cure” as such it 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 the tenacity of those involved. I hope the Trust can continue to support this programme as part of a broader portfolio.

It’s essential that the CF Trust works in conjunction with the CF Foundation and others to achieve a diversified portfolio of therapeutic options. We need to go after better spoons - more effective symptom-management tools (particularly those which can reduce inflammation or neutralise Pseudomonas and other lethal bugs) – as well as looking for new ways to rescue chloride channel function - to plug the holes.


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 establishing a more 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.

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 clinical practice more generally, to 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’m really excited by initiatives like CFUnite (backed by The Wellcome Trust), Cochrane and the James Lind Alliance; and the CF Trust’s commitment today to do more to facilitate patient involvement in this more strategic aspect of clinical trials.   


This is a big deal and we need to talk about it more. One of the most challenging aspects of having CF, for me, is the heavy burden of daily treatment. Every day I take about 40 pills, 7 nebulisers, a saline nasal rinse, 4 inhalers and do 2 or 3 injections, blood sugar tests and two sessions of self-administered physio. I spend a lot of time washing and sterilising nebuliser equipment. All this takes 3 hours on a good day and up to 4 hours when I am less well. This is my normal. When I get an exacerbation I typically need a 14 day course of hospitalised IV antibiotics. This tends to happen 2 or 3 times a year. I am lucky, for many it is much worse.

So CF adherence is not just popping pills - this is real work, it is difficult and it can be exhausting. You can never take a day off. 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. 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 mean simplifying treatments; developing a pill or inhaler to replace a nebuliser (more things like Bronchitol, TOBI Podhaler and Colobreathe); or more creative things, perhaps bringing in some sports psychology techniques; or web-based platforms or smartphone apps that help to manage and motivate or allow 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 the 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, big time, and I think it’s great that the Trust has highlighted adherence and reducing the overall burden of treatment as key research priorities. It’s a simple relation: reduce the burden, improve adherence; reduce exacerbations.

So here’s what I want you to take away:

The CF Foundation and Vertex have blazed a regulatory trail, given us new tools, shown Pharma that CF is a real market, shown everyone what can be achieved when Pharma works with a patient group. They have delivered a transformative drug for a very small sub-population of CF. I see this as injecting oxygen into the CF research environment. It’s woken people up. It’s like our Big Bang. We need to capitalise. We need to use it to our advantage. That’s why the Trust’s new strategy launch is perfectly timed. It provides a great scientific map but it also sends a clear signal of the Trust’s intent to collaborate with new partners, in new ways and to make resources available to help everyone in the CF community convert their ideas into new therapeutic tools.

And as Yoda said: “do or do not, there is no try".

Thank you."