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Life-saving drugs FAQs

Choose from the frequently asked questions below to find out more about our fight for access to life-saving drugs for everyone living with cystic fibrosis.

About precision medicines

What are precision medicines?

People with CF have two copies of a mutation of the gene that causes cystic fibrosis (CF). An example of precision medicine in CF could be a drug that targets one or a small number of these mutations (or ‘genotypes'). Each class of mutation affects the production of the Cystic Fibrosis Transmembrane Regulator (CFTR) protein (which controls the movement of salt and water in and out of cells in your body's organs) differently. This is why the Trust ran the Genotype Matters campaign, to highlight the importance for people with CF of knowing their genotype, as knowing it could make the difference between getting access to new medicines or missing out. Take a look at our mutations video to find out more.

What is a combination therapy?

A combination therapy combines more than one compound, which work together to impact the production or function of the CFTR protein, or otherwise improve lung function.

What is a triple therapy?

A triple therapy combines three drugs that perform different functions, including a potentiator and a corrector. These drugs work together to impact the production or function of the CFTR protein, or otherwise improve lung function.

What is a ‘corrector’ and a ‘potentiator’?

A corrector compound will help correctly fold the CFTR protein (as mutations mean the protein can’t correctly fold itself), and the potentiator helps opens the channel in CFTR to allow chloride out.

What is the drug pipeline?

The ‘drug pipeline’ is a phrase used to describe future medicines in the context of the journey each drug takes through the process of development in the laboratory, then through clinical trials to the availability on the NHS. The final trial stage, Phase IV (4), takes place when the drug has been made available publicly, to monitor its long-term efficacy in the real world. Find out more about clinical trials.

How are drugs appraised?

There are different appraisal bodies across the UK.

  • England – National Institute for Health & Care Excellence (NICE)
  • Wales – All Wales Medicines Strategy Group (AWMSG).
  • Northern Ireland – NICE/Department of Health and Social Care (DHSC).
  • Scotland – Scottish Medicines Consortium (SMC)

Once a new treatment has a licence, drug appraisal bodies weigh up the price a company has asked for against the clinical trial and other relevant data. They then recommend whether the drug will be clinically- and cost-effective for the NHS, in the context of available budget.

The NHS is legally obliged to fund drugs recommended by these bodies. However, it also works the other way. If a drug is not recommended, then the NHS is not obliged to fund it.

How are drugs appraised by the EMA?

A new treatment needs to be given a licence for use before it is appraised for clinical- and cost-effectiveness in any nation in the UK.

The European Medicines Agency (EMA) grants this licence, which is called Marketing Authorisation, after it has analysed whether a new treatment is both safe and clinically effective. It makes no judgement on the cost of a new medicine when deciding whether or not to grant a licence. Find out more about how drugs are tested in clinical trials.

Orkambi and Symkevi

Are Orkambi and Symkevi available on the NHS?

In 2019, NHS bodies across the UK reached managed access agreements making Orkambi, Symkevi and Kalydeco available on the NHS to eligible adults and children with cystic fibrosis. Speak to your CF team for more information. These managed access agreements were updated in the summer of 2020 to include the triple combination therapy, Kaftrio, to the deals. Speak to your CF team for more information.

What must happen before I can start taking Orkambi and Symkevi?

You may be required to take a few tests before beginning a CFTR modulator therapy. These tests may include checking your eye and liver health. The tests required will depend on your age and health, and therefore will be decided by your CF team.

How is the Trust supporting the roll out of Orkambi and Symkevi?

CF centres are doing everything they can to roll out all available modulator therapies as fast as clinically possible. Centres need to undertake testing and monitoring when placing a patient on a modulator and this can slow the rollout.

The Trust has worked closely with the NHS and the UK CF Medical Association to support CF teams with information.

Will I be able to stop my other medications and treatments?

Do not stop any of your medications or treatments without first speaking to your CF team. Studies are underway and in development to explore whether these drugs can reduce the number of other treatments people with CF take.

Will I still have to worry about cross-infection?

People with cystic fibrosis who have been prescribed CFTR modulators such as OrkambiSymkevi and Kalydeco are still susceptible to infection and should be aware of and take precautions against cross-infection. These drugs are able to reduce infections that would require hospitalisation, but there is currently no evidence to suggest that they can prevent them altogether and therefore there is still a significant risk of cross-infection between people with CF and close contact should be avoided. You should speak with your CF team if you have any questions or concerns.

Can I take Orkambi or Symkevi if I have received a lung transplant or other organ transplant?

Currently available modulator therapies are listed as contraindicated in patients with organ transplants in the British National Formula and as not recommended in the summary of product characteristics. We are aware of case reports of people successfully receiving Orkambi following liver transplant. You should therefore always speak to your CF Team and transplant team about your circumstances.

Studies are in development to explore potential use of these drugs in people who have had different organ transplants including lung transplants to better understand the impact, risks, and the impact they could have.

When will Symkevi be expanded to younger age groups?

The EMA adopted a positive opinion for the expansion of Symkevi to children with CF aged 6–11 on 18 September 2020. Now the EMA have given the green light for this extension, the European Commission is expected to formally grant a licence extension. As part of the deals negotiated by the NHS across the UK, this licence extension will automatically apply to the UK once granted.

Are the deals the same in each nation?

All the nations have equivalent agreements with Vertex Pharmaceuticals. This means that people with CF will have access to Orkambi and Symkevi while further data is collected on their efficacy The terms of the UK deals also mean that as many as 300 patients with some rarer genetic mutations, which fall outside of the scope of the European licensing body’s considerations, will now be able to benefit from Symkevi and Kalydeco.

I’ve read that these deals are only interim, why is that and how long are they for?

NHS bodies across the UK have reached managed access agreements that are between two and five years. During this period, data will be collected to monitor the effectiveness of the drugs. This data will be submitted again to NICE for appraisal. This supports the process NHS England uses to decide which drugs are clinically and cost effective, while giving the opportunity for real-world data on the efficacy of the drugs to be part of the appraisal. The real-world data collection agreement will last for 18 months, prior to a NICE appraisal that is expected to conclude in September 2021 to inform a new agreement between the NHS and Vertex.

Chief Executive of NHS England, Simon Stevens, wrote a letter to Westminster’s Health and Social Care Committee setting out some details of the deal.

What will happen when the interim period runs out?

People with CF will continue to have access to these drugs. As part of the interim access deals, Vertex Pharmaceuticals also agreed to a flexible contractual mechanism, which means that in all circumstances all three drugs will continue to be available following completion of the NICE and SMC appraisals. Following appraisal, new deals will be negotiated between the NHS and Vertex based on the added real-world data collected as part of this initial deal.

How are long-term safety and side effects being monitored?

The UK CF Registry will be collecting real-world data from consenting people with CF as part of the agreements in the UK for Orkambi and Symkevi, to monitor effectiveness. You can read more about the Data Collection Agreement here. Any safety concerns or side effects should be reported to and discussed with your CF team.

Can I take part in clinical trials if I am on Orkambi, Symkevi or Kalydeco?

Someone taking a CFTR modulator such as Orkambi, Symkevi or Kalydeco will be excluded from another CFTR modulator clinical trial, unless they are willing to stop taking their CFTR modulator for four to 12 weeks prior to entering and throughout the duration of that trial. However, they wouldn’t necessarily be excluded from other clinical trials that are trialling non-modulator therapies. The entry criteria for every trial is unique, and you should speak to your CF team if you are interested in taking part in a clinical trial.

Triple combination therapy (Kaftrio)

What is Kaftrio?

Kaftrio is a 'triple-combination therapy' made up of three different compounds, tezacaftor and ivacaftor (which together make up Symkevi) combined with elexacaftor.

Why is the drug called Kaftrio?

Trikafta is the US name for the triple combination therapy, whereas the drug has the brand name Kaftrio in Europe. The two names refer to the same drug.

Who will be eligible for Kaftrio?

The European Commission has formally licensed Kaftrio for use by people with CF who:

  • are aged over 12
  • have two copies of the F508del mutation or one copy of F508del and one copy of a 'minimal function’ mutation. The details of which precise genotypes the latter group covers is to be confirmed.

This decision by the EMA is different to the one made by the FDA in America, who allow the drug to be prescribed to people over 12 who have at least one copy of the F508del mutation. The various drug regulatory bodies across the world take different approaches to how they interpret evidence on the safety and clinical effectiveness of new drugs and ultimately what licence indication should be granted.

How do I find out if my mutations are eligible?

We know many of you are anxiously waiting for news on which mutations will be eligible for Kaftio. We, and CF teams, are working hard behind the scenes to get Kaftrio to everyone who could benefit, as quickly as possible. Vertex has launched an online tool for CF clinicians, which will enable CF teams to fully identify options for their patients. Together with the UK CF Medical Association, we have notified clinicians that this online tool is now available.

What effect does Kaftrio have?

In clinical trials for Kaftrio, people with two copies of the F508del mutation had a 10% increase in lung function compared to treatment with Symkevi, and people with a single copy of F508del and a minimal function mutation had more than a 14% increase in lung function compared to treatment with the placebo.

Clinical trial data show that many people taking Kaftrio will have improvements in gastrointestinal (GI) issues and overall quality of life. Further studies are underway to better understand the long-term effects Kaftrio will have on the overall health of people with CF, including infections, inflammation, mucus clearance, Gl health, blood sugar, growth, and liver function.

Kaftrio has shown to be safe and effective, with potentially fewer negative side effects than previous licensed modulators.

When will Kaftrio be available?

Following formal licensing by the European Commission, clinicians across the UK are now able to start prescribing Kaftrio to eligible patients.

NHS England announced on 30 June 2020 that a deal had been agreed for Kaftrio. This was followed by similar deals in Wales on 22 July, in Northern Ireland on 30 July and in Scotland on 4 August, with Vertex to facilitate access from the first day the European licence is granted.

The deal with NHS England included 'tag along rights' for the other devolved nations that paved the way for similar deals across the UK. We are seeking more information and updates about negotiations and access in the Crown Dependencies of Jersey, Guernsey, and the Isle of Man.

Now CF teams can prescribe Kaftrio, it will take time for teams to organise and roll-out Kaftrio. The Trust will work closely with the UK CF Medical Association to support roll-out and ensure everyone can start Kaftrio as fast as clinically possible. 

What is the Trust doing to support access to Kaftrio?

We are working with all key stakeholders to support access to everyone in the UK who could benefit. We are seeking more information and updates about negotiations and access in the Crown Dependencies of Jersey, Guernsey, and the Isle of Man. We understand there are different mutation eligibilies covered in the deals agreed in England, Wales, Northern Ireland and Scotland so it is important to check with your CF team about which modulators you may be eligible for.

We are working with the UK Cystic Fibrosis Medical Association to support plans for roll-out to ensure everyone can start Kaftrio as fast as clinically possible.

We also support the UK CF Registry, which will continue its valuable work in monitoring the effectiveness of this drug, among many others.

Are there other therapies like Kaftrio being developed?

It is difficult knowing that not everyone will stand to benefit from Kaftrio or the other currently licensed modulators.

At least three companies, including AbbVie, Proteostasis Therapeutics and Vertex Pharmaceuticals, are developing other potential triple combination therapies. Through our Clinical Trials Accelerator Platform, we are actively working to support the ongoing HIT-CF Europe research project which aims to provide better treatments for people with rare CF mutations who are ineligible for Kaftrio.

We are here for everyone with cystic fibrosis and we know there is more to do to ensure everyone with CF has access to life-saving drugs. Read more about the Trust’s commitment to no-one left behind.

Will I be able to stop my other medications and treatments?

Do not stop any of your medications or treatments without first speaking to your CF team. Studies are underway and in development to explore whether these drugs can reduce the number of other treatments people with CF take.

Will I still have to worry about cross-infection?

People with cystic fibrosis who have been prescribed CFTR modulators such as Orkambi, Symkevi, Kalydeco and Kaftrio are still susceptible to infection and should be aware of and take precautions against cross-infection. These drugs are able to reduce infections that would require hospitalisation, but there is currently no evidence to suggest that they can prevent them altogether and therefore there is still a significant risk of cross-infection between people with CF and close contact should be avoided. You should speak with your CF team if you have any questions or concerns.

Can I take Kaftrio if I have received a lung transplant or other organ transplant?

Currently available modulator therapies are listed as contraindicated in patients with organ transplants in the British National Formula and as not recommended in the summary of product characteristics. Kaftrio is not expected to improve lung function in patients following a lung transplant as the effects of these drugs have not been studied and there is a risk that they could interact with the immunosuppressive drugs that are needed to stop the body rejecting the new organ.

For individuals who have had another organ transplant, or specific personal circumstances, your team may recommend Kaftrio if they think it will treat your condition effectively and the benefits are greater than any risks. You should therefore always speak to your CF Team and transplant team about your circumstances.

Studies are in development to explore potential use of these drugs in people who have had different organ transplants including lung transplants to better understand the impact, risks, and the impact they could have.

When will Kaftrio be expanded to younger age groups?

In September 2020, Vertex announced positive clinical trial results for the use of Kaftrio for children with CF aged 6–11. We are not in a position to predict the timings for submitting trial data for regulatory approval, but Vertex have stated they intend to submit an extension application to the FDA later this year, followed by regulatory submissions in other countries. It is likely that a submission for an extension to the EMA will be after the FDA, with a decision being made in 2021.

In addition to Kaftrio, the EMA adopted a positive opinion for the expansion of Symkevi to children with CF aged 6–11 on 18 September 2020. Now the EMA has given the green light for this extension, the European Commission is expected to formally grant a licence extension. As part of the deals negotiated by the NHS across the UK, this licence extension will automatically apply to the UK once granted.

What about expanding to further genetic combinations?

In July 2020, Vertex announced positive results from their phase III clinical trial testing the safety and effectiveness of Kaftrio for people with one copy of F508del and one copy of either a residual function or gating mutation. This data was submitted to the EMA in September 2020, to support a Type II Marketing Authorization Application which, in essence, intends to expand the eligibility of Kaftrio to anyone over 12 with at least one copy of F508del.

Compassionate use

What is compassionate use?

Compassionate use provides access to medicines that are not otherwise available on the NHS to people in critical need, where attempts to treat them with licensed medicines have been exhausted or there is no appropriate licensed treatment available. Compassionate use is sometimes also called ‘expanded access’ or ‘early access’. Please speak to your CF team to find out about compassionate use eligibility.

Can I still be considered for compassionate use therapy through compassionate if I am already on Orkambi or Symkevi?

If you are already receiving a CFTR modulator therapy but your health state is critical and you feel you may benefit from a different treatment, our advice is to speak to your CF team.

Other FAQs

What happens in the EMA process?

The EMA carry out an analysis of all the data that a pharmaceutical company submits about a treatment, assessing its safety and clinical effectiveness. A committee of experts called the Committee for Medicinal Products for Human Use (CHMP) carry out the evaluation, which includes questioning the pharmaceutical company and seeking advice from other experts, healthcare professionals and patients.

The EMA does not have the power itself to grant a licence. Instead they offer a recommendation to the European Commission as to whether a drug should receive its licence – known as a Marketing Authorisation. The evaluation by the EMA does not make a judgment on the cost of a new medicine either. When a Marketing Authorisation is granted, it is up to individual countries within the EU to negotiate a deal with the pharmaceutical company for access to the drug. The EMA has produced an interactive timeline showing the journey a medicine takes during their assessment.

What opportunities are there to join clinical trials for CFTR modulators?

You can find an array of information about taking part in clinical trials, as well as our very own CF Trials Tracker, a CF clinical trials database to help you find suitable clinical trial opportunities.

What is the Trust doing for people who will not benefit from current CFTR modulators?

The Trust continues to fund and support ground-breaking research into innovative new medicines for all people with CF, whatever their genotype. This includes research into a range of personalised medicine approaches to treat the underlying causes of cystic fibrosis. The Trust will also support, where possible, pharmaceutical companies that aim to develop medicines that are applicable to rare CF mutations, and strive to support people with rare CF mutations to become involved in any relevant future clinical trials, via our Clinical Trials Accelerator Platform.

More details on activities of the Trust to support research for all people with CF can be found here.


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