SPOTLIGHT: Kaftrio Life Before & After

Tomas Thompson is a PWCF and former patient advocate for Cystic Fibrosis Ireland. A much respected member of the CF Community, Tomas is now working to research and develop medical devices to improve CF care. In this article Tomas talks about the timeline and development of Kaftrio and gives his own personal perspective about the impact of this new and innovative drug therapy. This article outlines one person's experience. As with all drug therapies, each person will have a different impact from Kaftrio. Further information on the roll out of Kaftrio can be found on page 2 or online at www.cfireland.ie

I am a child of the late 70s and was born when the outlook for PWCF was very different than today. Back then CF was mostly seen as a childhood condition as many PWCF didn’t make it to adulthood, those that did had a very different quality of life to PWCFs today.

The treatments available when I was growing up in the 70s & 80s were limited and the research into the CF was only at its infancy. Members of CF Ireland at the time just like today, did all they could to push to speed up the development of new facilities and treatment. In years gone by and prior to understanding of the risks of cross infection, all CF Associations worldwide brought children with CF together for summer camps and similar joint activities. CFI was no different and one initiative was that every year CFI would rent a plane, fill it with as many CF families as they could, flying them to Lourdes to take ice baths and pray to St. Bernadette as this was seen as the best option of a cure at the time!

To many this might seem strange today for many reasons, but these families formed the backbone for many years of organisations such as CFI, CF Trust & CF Foundation (CFF) in the US, who raised the funds by any means necessary which without we would not now have the treatments we have today.

In the 90s the research sped up around the world, but for PWCF and their families it was slow, with many highs and lows over that decade as promising research into gene therapy failed to bring the desired results and the dreams of the late 80s when they discovery the CF gene was fading, as one approach after another was failing to translate in to an effective treatment.

A vast effort was spent on research in the 90s to little effect, but in the early 2000s the US Foundation took a new approach headed up by Robert Beall, he went searching for a drug company that would try to take on CF head-on. That search led him to Aurora Biosciences, a San Diego company. In 2000, the CFF agreed to fund drug discovery work in cystic fibrosis at Aurora with $47 million investment over five years, this is the single most important investment made in CF since the discovery of the CF gene, as one year later, Vertex bought Aurora.

Aurora had been developing modulator drugs that treats the inactive CFTR protein in the CF cell which is the underlying cause of CF. This discovery eventually led to Vertex's development of Kalydeco (Ivacaftor) which proved life changing for 10% of the PWCF population who had the gene G511D, but also give hope to PWCF that a medication for all could now be on the horizon.

Viewing from the side-lines were the vast majority of PWCF (80%) in Ireland and worldwide, who had the CF mutation double D508 or one copy of D508 in some shape or form. The race was then on to develop a modulator for people with double D508 or one copy of D508. This led to the launch of Orkambi (lumacaftor/ivacaftor) in 2017, which was the first modulator that would work for me as I am double D508.

Around that time I was having lots of infections and was in and out of hospital more than ever, so much so that in the 12 months before starting Orkambi I had spent more than 100 days in and out of hospital. That time in my life was not only hard on me, but for my partner Paula, and our families. As my lung functions was decreasing at a rate of between 1% - 2 % per year, keeping on top of everything was hard work for us all - lots of IVs, constantly in and out of hospital. Other PWCF families like us know what it’s like, the inability to plan around school, college, work, holidays, birthdays and family events, in and out of hospital, living week by week; the rest of the world has now also experienced a little of what’s it like, as we all have to learned to live with Covid -19.

Looking back Orkambi was very positive for me, but unlike Kalydeco it did not deliver much of an increase in lung function as it did for PWCF on Kalydeco. For many Orkambi was hard to tolerate. Some of the side effects meant people had to come off it or could not take it from the start, for me the only issue was some chest tightness, but at the time it led to better quality of life for me and Paula.

Orkambi was quickly followed by Symkevi (ivacaftor with tezacaftor) two years later and thanks to the pipeline agreement former Health Minister Simon Harris made, it allowed us to start on to it. Symkevi was better tolerated for many and for me I found it much better. I no longer had the chest tightness and I held my weight better without the use of daily feed supplements. Again, Symkevi slowed my lung function decrease allowing me to hold my base line lung function over the years, but still no increase.

The holy grail was still to develop a modulator that could match the results seen with Kalydeco for people with D508.

So along comes the 4th modulator drug from Vertex in just 8 years called Kaftrio (ivacaftor / tezacaftor / elexacaftor). The key difference this time around is that Kaftrio is a triple combination that works in conjunction with Kalydeco taken once a day to normalise the CFTR activity in CF cells for almost 90% of PWCF with double D508 or one copy of D508. The good news was the research results of Kaftrio mirror that seen in Kalydeco 8 years earlier.

I only started Kaftrio 5 weeks ago but the medication took affect within hours. First I experienced what is being called the “purge”-within 48 hours I removed large amounts of mucus from my lungs with ease, I slept for 14 hours straight that night as I felt the effects of Kaftrio all over my body, it was unlike any of the other modulators I had taken before. As the days went on I felt so much better, no mucus, no cough, better appetite, I thought this is super for the first few days, expecting the mucus and cough to return in some shape or form, but as the weeks went on the cough reduced to a fraction of what it was, the mucus was still 95% less and clear.

Four weeks later I had put on 3.7kg and most importantly my lung function increased by 11% in just 4 weeks!

Not only is this game changing, its life changing, for me and for many others it has not only stopped the decline in lung function but reversed it. The study data is showing the average increase is around 14% in PWCF and yes there have been some side effects in PWCF but not yet for me. If they come, we will deal with them. But like much of life with CF it’s not always about the numbers, I feel much better, have more energy and we can now see that there is a modulator that works for us that is equal to or better than what we have seen with Kalydeco.

When Vertex’s first drug came out, we knew they had cracked the code and that a drug would eventually come for us but time was always the issue, how long do we need to wait. For many PWCF they didn’t have that time and we need to remember them and the good fight they fought. Vertex has committed to find that medication for the outstanding mutations and to ensure all PWCF in every region can get access to it and no doubt the rest of the CF community will not rest until that time comes.

Kaftrio and Kalydeco will not only add years to my life but just as important, it will add life to those years, and for many others with CF also. Kaftrio and Kalydeco will become the gold standard for the treatment of CF in the years ahead, it will reduce the numbers needing transplants, hospitalisations, reduce the hours of daily treatment, medications, physiotherapy we all need currently. No longer will a PWCF born today need to think that their future is any different to their brother or sister, classmate, or colleagues.

So as you can see we have come along way and many people have helped lay the foundations for change over the years, it’s like a relay race where one generation passes the baton to the next to get us across the line. Kaftrio is getting us near that line, it’s like finding the Covid-19 vaccine for the rest of the world for us.

There is an old Egyptian Proverb that says "Health is a golden crown, placed on the brow of the healthy that only the sick can see".

Once available to all, Kaftrio could be that golden crown for the CF community, and will go a long way to answering all those prayers to St. Bernadette from the families in the past who did so much for CF. Kaftrio will free PWCF to live a normal life, we will no longer need to keep safe by staying apart (which we have done for many years) and someday in the near future the CF community will all meet up again safely. Now I believe that we have a truly game changing medication in Kaftrio, the challenge for PWCF will change again - to simply living a normal life.