Campaign for Kaftrio

The Kaftrio Dispute

Frequently asked Questions (FAQ’s)

1. What is cystic fibrosis?

Cystic fibrosis (CF) is a progressive, genetic, long-term disease that affects the lungs, digestive system, including the solid organs of the pancreas and liver and other organs. In people with CF, mutations in the CFTR gene cause its protein to become dysfunctional leading to mucus in various organs to become thick and sticky. In the lungs, this sticky mucus clogs the airways and traps germs like bacteria, leading to infections, inflammation, respiratory failure and other complications.

2. How many people are affected by cystic fibrosis in Ireland?

Ireland has the highest rate of CF per capita in the world, with approximately 1,400 children and adults in Ireland living with the condition.

3. What is Kaftrio®?

Kaftrio® is the newest of four CFTR modulator therapies. It is a triple therapy combining the drugs Elexacaftorwith Tezacaftor and Ivacaftor. These modulator therapies are designed to correct the malfunctioning protein made by the CFTR gene. Because different mutations cause different defects in the proteins, these medications are effective only in people with relevant mutations. These modulator therapies work to make mucus in the lungs and other organs less thick, thereby helping to relieve symptoms of the disease.

4. What have studies shown about how Kaftrio® helps people with cystic fibrosis?

In one of the original clinical trials for Kaftrio®, 403 people with CF age 12 and over, who had one copy of the F508del CFTR mutation and another defined mutation, participated in a 24-week study. Approximately half the group took Kaftrio® and the other half took a placebo. In the group which took Kaftrio®, their lung function improved significantly. They experienced fewer pulmonary exacerbations, including 71% fewer pulmonary exacerbations that led to hospitalisations, and 78% fewer pulmonary exacerbations that led to intravenous antibiotics. They had a significant improvement in their CF respiratory symptoms. The symptoms measured included: waking up from coughing, congestion, wheezing, cough, mucus production and difficulty breathing. They also had a significant increase in their body mass index (BMI) compared to those taking placebo.

5. What has the EMA decided in relation to Kaftrio®?

The EMA has found Kaftrio® to be an effective treatment for patients with CF who have at least one F508del mutation in the CFTR gene. These patients have a high unmet medical need. In terms of safety, Kaftrio was well tolerated. Therefore, the EMA has decided that Kaftrio’s benefits are greater than its potential risks and so it can be authorised for use in the European Union.

6. Who has it licensed Kaftrio® for?

The EMA has licensed Kaftrio® for use in people with cystic fibrosis age 6 years and above who have at least one copy of the F508del mutation in their CFTR gene.

7. If Kaftrio® has been approved for 6-11-years-olds, why are some children getting it In Ireland and others not?

Kaftrio® has been licensed in Europe for use in people with cystic fibrosis age 6 years and above who have at least one copy of the F508del mutation in their CFTR gene. A 10-year portfolio agreement was signed by the HSE and Vertex in 2017 to bring access to a suite of Vertex-developed CF treatments. In Ireland, Kaftrio® is currently only reimbursed for people with CF who are: • age 12 and older and have at least one copy of the F508del mutation • age 6 and older and have two copies of the F508del mutation • age 6 and over and have one copy of the F508del mutation and a second listed mutation. This list excludes a subset of patients who have one copy of the F508del mutation and a genotype with an unclassified or minimal function

8. The National Centre for Pharmacoeconomics (NCPE) says that the 35 children age 6-11 were approved in the initial deal with the HSE and that the pharmaceutical company has already been paid?

The HSE and Vertex would seem to disagree on this point. Cystic Fibrosis Ireland has not seen the details of the original agreement, and so has no information on this.

9. The pharmaceutical company disagrees that it has already been paid and has said it is now happy to offer the drug for the same price for which the other children receive it – what is CFI’s view?

This this not really a question Cystic Fibrosis Ireland can answer as we do not know the details of the original deal and whether an overall price was agreed for the therapies for the entire CF community, irrespective of the number of patients accessing same, or if it was on the basis of an agreed cost per person and/or a specific genotype. CFI calls on Vertex to make Kaftrio® as affordable as possible. Cystic Fibrosis Ireland strongly believes that anyone who stands to benefit from the life-changing drug Kaftrio® should have access. The HSE and Vertex have a moral duty to get around the table and hammer out their differences, and not delay a resolution of this matter any further.

10. Where do you think fault most lies?

The responsibility for making sure that all children who could benefit from Kaftrio® and have access to the treatment lies with both the HSE and Vertex and we implore both of them to redouble their efforts to find a solution as soon as possible. The HSE’s vision is “a healthier Ireland, with the right care, at the right time and in the right place”. Vertex Pharmaceuticals declares among its values that “patients are at the centre of all that we do… every decision we make is driven by the patients we serve”. Both organisations need to reflect on these commitments.

11. Would you call on the HSE and the pharmaceutical company to publish the deal so we can all see it?

Confidential pricing agreements can provide the opportunity for better deals to be agreed between the State and industry. Equally, as is apparent here, they can hamper transparency in ensuring equality of access to essential medicines such as Kaftrio. Cystic Fibrosis Ireland believes that independent arbitration, conducted quickly and efficiently, presents a way forward in a situation of continuing disagreement among the parties over the content of the deal.

12. What do you say to the NCPE argument that “the price doesn’t match the benefit at this point in time” and that “we’re overpaying for these drugs”?

The HSE has previously accepted the benefits of Kaftrio® and agreed a price with the company for the 690 people with CF who are already receiving it – people who can testify to its value in the real world. The benefits have been clearly demonstrated in clinical trials showing improvement in lung function, reduced exacerbations, reduced hospitalisation, reduced need for intravenous antibiotics, etc. There are 11 other European countries that provide Kaftrio® to all 6-11 year olds included in the EMA recommendation, presumably these deals are not greatly dissimilar to Ireland’s pipeline deal of 2017?

13. You say that there will be a gain for the HSE in other areas of care – what are these?

In one of the original clinical trials for Kaftrio®, in the group which took Kaftrio®, lung function improved significantly. They experienced fewer pulmonary exacerbations, including 71% fewer pulmonary exacerbations that led to hospitalisations, and 78% fewer pulmonary exacerbations that led to intravenous antibiotics. These clearly demonstrate savings to a health service.

14. Do we know how much this is costing the health of these excluded children while they wait provision of the therapy, or until they reach 12 years of age where they would be offered treatment?

Every person with cystic fibrosis is different and will have a different response to the condition. We can say that in a progressive condition like cystic fibrosis, delayed treatment will mean the disease will continue to diminish the body’s organs. While we cannot be specific about the pace or extent of this deterioration, or whether it can be reversed, it is clear that it is morally wrong to withhold treatment from patients when we know that they could benefit from it. Healthcare delayed is healthcare denied.

15. Would referring Kaftrio® to the NCPE for a Health Technology Assessment be a good idea?

No. In May 2022, after a rapid review, the NCPE recommended that a full Health Technology Assessment (HTA) be carried out to assess the clinical effectiveness and cost-effectiveness of Kaftrio®. This seems bizarre in the extreme, given that the therapy is already being provided to significant numbers of people with Cystic Fibrosis in Ireland. We would be very concerned that parents would perceive this as a negotiating ploy or a delaying tactic, that can take up to 90 days to complete, but in which a “stop-clock” process applies where further information can be sought, meaning further delay. Given the NCPE’s position on Kaftrio®, in which it has already stated its concerns about its cost-effectiveness, we are only going to end up right back where we are now with a recommendation from the NCPE that it be approved but not at the price on the table. Back to square one, but months of delay later.

16. There is a private members’ Bill before the Dáil at the moment to change how orphan/ rare disease drugs are assessed and reimbursed – how would this work, would this make the assessment of such drugs fairer?

Yes. The Health (Pricing and Supply of Medical Goods) (Amendment) Bill 2021, aims to establish more meaningful criteria in deciding on reimbursement for orphan/rare disease medicinal products. This Bill is at present supported by Government. Under the existing legislation, there is no differentiation between orphan/rare disease medicinal products and other more broadly applicable products in Ireland. All new medicines must undergo the same HTA. Right now, the HTA assesses cost-effectiveness using a willingness-to-pay threshold of up to €45,000 per

quality-adjusted life year gained. This means that a medicine is considered cost-effective if it costs up to €45,000 or less to achieve one additional year of a perfect quality of life. We know that the market opportunities for drug companies to make profits from orphan/rare disease drugs are lower given smaller population sizes for rare diseases. This can lead to higher pricing of orphan drugs. These higher prices, limited data from clinical trials, and often lack of a comparator drug, push orphan drugs out of the threshold of €45,000 per quality-adjusted life year gained and so these medicines continually struggle to secure reimbursement. The odds are stacked against them. In short, drug therapies for rare/orphan diseases in Ireland are not treated fairly at present.

17. Are drug pipeline deals a good Idea?

Yes. The innovative pipeline deal agreed between the HSE and Vertex meant that access to new therapies, or extensions to current therapies, would be provided once they were approved by the EMA. To date this innovative approach negotiated by the HSE has avoided disputes such as this one. Similar pipeline deals have provided access to Kaftrio® in the UK and Denmark (for example). Ireland though, was the first country in the world to develop a pipeline approach for any suite of drug therapies and this has been lauded and adapted by other countries. The NCPE has recently stated that it is not in favour of pipeline deals. This is very disappointing and an outmoded position, in our view, and is at odds with the HSE/Vertex agreement of 2017.

18. What do you say to people who say this is taxpayers’ money that is going to line the pockets of pharma companies, that could be better spent on other cheaper medicines for greater numbers of people?

It is not equitable to deny access to a lifesaving drug based on the rarity of a person’s condition. If you compare someone with a severe, but common condition, and someone with a severe, but rare, condition, our current system disadvantages those with rare conditions. The research and development costs of a drug are shared among more people in the common group, resulting in a lower cost per drug than in the rare group, where research and development costs are shared among a smaller patient pool. While the costs may be higher for an orphan drug, the medical needs of both patients, and potential lifesaving benefits of the drug are the same. Cystic Fibrosis Ireland does not believe it is fair or equitable to provide access to medicines to one person with one severe, more common, disease but not to another equally severe, but less common, disease.

Cystic Fibrosis Ireland fully supports the HSE in seeking value for money and a fair and accurate price for drugs. The current system, however, is not fit for purpose when it comes to rare disease drugs.

19. What does Cystic Fibrosis Ireland want to happen now?

Cystic Fibrosis Ireland has always campaigned on the principle “no child with CF left behind”, that all those who stand to benefit from therapies such as Kaftrio® should gain access. The responsibility for making sure that all children will benefit lies with both the HSE and Vertex and we implore both of them to redouble their efforts to find a solution as soon as possible. If the parties cannot agree, then a swift independent arbitration process should be undertaken to review the deal previously agreed to determine whether the deal already covers the “Kaftrio 35”. If it does, then the company should honour that. If it doesn’t, then both parties need to agree a new deal without further rancour or delay.

A reflection by Sharon Deignan, CF/ Respiratory Clinical Nurse Manager Childrens University Hospital Temple Street

A nurse stopped me on the corridor a few weeks ago and said “Do you ever think about Katie*?” I replied “I think about her all the time”. Her eyes filled with tears, as did mine. “Do you remember everything about her?” We actually held hands and spent a few moments laughing and smiling and crying remembering our beautiful patient Katie, who had Cystic Fibrosis. This beautiful, wonderful girl was born before newborn screening, before the advent of CF specialist centres and before modulator therapies. Despite this, she like many patients with CF had a strength of character, personality, courage and resilience, which allowed her to live a life full of promise and determination. I loved her humour, her wittiness, her smile, her ability to lift and lower your heart all in the same moment. It was 2007. I just started my job as a nurse specialist in the CF unit in Temple Street Children’s hospital. Katie rocked out of the lift on floor 2 and took one look at me and said “Where’s Mary?” Katie knew fine well that if she was looking at my face, Mary was on a day off, as we job shared! I may have completed an interview to get the job, but the real interview began that day! Katie did not suffer fools and could analyse your abilities quickly. Honesty was your best friend and then slowly but surely when trust was established, she would open her heart and allow you in. This approach she perfected during hospitalizations. This approach of earning her trust was unanimous with all members of the CF team, and indeed all staff within the hospital. I remember Claire our physiotherapist, discovered that Katie loved a good foot massage. So that’s exactly where she started. The day could go very well if Claire started with her feet and slowly but surely made her way up to her lungs to complete chest physiotherapy. Medical and nursing students went through the same vigorous process. Katie was very quick to point them in the right direction (which was out the door!) if she wasn’t in form for questions or interruptions. Mostly, she loved the medical and nursing students, as they passed the time for her. She had an inquisitive and curious mind and was always interested in what part of the world they travelled from, particularly the students from Royal College of Surgeons. By the end of their learning placements she had them sponsoring her school raffles, readathons and clearing out all the trick or treat badges for Temple Street. Sadly, Katie lost her battle with CF at the tender age of the 16. Always loved and never forgotten. So much has happened in the last decade. Newborn screening in 2011 has allowed the early identification of CF, and thereby facilitates early access to specialist CF care. Knowledge and education regarding the early treatment of infection, control of infection and spread of infection, have all been huge contributors to the improved outcomes for patients with CF. And of course, modulator therapies have been transformative, which brings me to the current quagmire of right vs wrong. It is simply wrong to deny these 35 children access to a medication that we know to be highly effective. I also think about the babies, toddlers and pre-schoolers who attend our service and are also in this “HET/MIN” group, so the number is actually 35+. In this era of health economics and value related healthcare, is it not already known that prevention is better than cure? These children deserve the best chance of living a full life with CF. They deserve the opportunity to plan for a future which is full of fun, activity and promise. These children cannot and should not be left behind. Yours, Sharon Deignan