What are precision medicines?
People with CF have two copies of a mutation of the gene that causes cystic fibrosis. 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 bodies 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 license, 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 the UK.
The European Medicines Agency (EMA) grants this license, 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 license. Find out more about how drugs are tested in clinical trials.
When will Orkambi and Symkevi be available to people with CF?
NHS bodies across the UK have 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.
What must happen before I can start taking Orkambi and Symkevi?
You may be required to take a few tests before beginning Orkambi, Symkevi or Kalydeco. 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.
I am still waiting to hear when I can start Orkambi and Symkevi – why is this?
Cystic fibrosis teams can now prescribe Orkambi and Symkevi, but this does not mean you will necessarily be started on it straight away. All CF centres are working to get eligible patients on to these drugs as soon as clinically possible. If you are concerned about timescales you should contact them for an update.
What is the Trust doing to speed up the roll out?
CF centres are doing everything they can to roll out Orkambi and Symkevi, as fast as clinically possible. Centres need to undertake testing and monitoring when placing a patient on Orkambi or Symkevi 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 Orkambi, Symkevi 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?
It is currently not recommended that any CFTR modulators are taken by anyone who has had a transplant, as the effects of these drugs for transplant patients has not been studied. Studies are in development to explore potential use of these drugs in people who have had an organ transplant.
When will Symkevi be expanded to younger age groups?
Vertex announced positive clinical trial results in early 2019 for the use of Symkevi in people with CF aged six to 11. They intend to use these results in an application to the EMA to expand the eligibility of Symkevi for people in the EU. The EMA will have to approve the age expansion before Symkevi becomes available to people aged six to 11 in the UK.
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 whilst further data is collected on their efficacy.
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 appraisal. Following the NICE appraisal, a new deal will be negotiated between NHS England and Vertex based on the added real-world data collected as part of this initial deal.
What happens if I am already in receipt of Orkambi or Symkevi through compassionate use or as part of a clinical trial?
All individuals in England currently receiving one of these drugs, either through compassionate use, or as part of a clinical trial, will continue to do so under the new agreement with Vertex Pharmaceuticals.
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.
When will the triple combination therapy be available to people with cystic fibrosis?
The triple combination therapy (known as Trikafta is the US) is Vertex Pharmaceuticals’ latest CFTR modulator.
The triple combination therapy was approved in the United States for those aged 12 and over who have at least one copy of the F508del mutation. Vertex has submitted the drug to the European Medicines Agency (EMA), who are analysing it for safety and clinical effectiveness, with further updates expected in 2020. We will continue to support the evaluation process, engaging wherever possible, to ensure that the triple combination therapy can be made available to people with CF as soon as possible. The EMA has indicated that this medicine will be reviewed under accelerated assessment, meaning a decision will be reached typically within seven to eight months. A decision is expected before the end of 2020.
What happens in the EMA process?
The EMA will carry out an analysis of all the data Vertex submits about the triple combination therapy, 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 drug’s developer and seeking advice from other experts, healthcare professionals and patients.
This evaluation by the EMA does not make a judgment on the cost of a new medicine when deciding whether or not to grant a licence. When this licence - called a Marketing Authorisation - is granted, it is up to individual countries within the EU to negotiate a deal with Vertex for access to the drug. The EMA have produced an interactive timeline showing the journey a medicine takes during their assessment, which can be found here.
Is the triple combination therapy part of the current deals across the UK? Why wasn’t it included?
Access to the triple combination therapy was not included in this deal as it has not yet been authorised for use in the EU by the EMA. However, this deal does commit Vertex to submitting the triple combination therapy for NICE appraisal in the UK once it has been given its Marketing Authorisation by the EMA.
Can we use the Accelerated Access Review (AAR) to speed the process up?
The AAR was an influential government report that suggested changes to the way new drugs are appraised and negotiations over pricing conducted. One of the main outcomes was to establish the Accelerated Access Collaborative and a Commercial Medicines Unit within NHS England, who negotiate fair and sustainable prices for new medicines. This unit offers a range of commercial options for pharmaceutical companies wishing to enter the UK market, with the potential for a deal to be reached sooner. However, while there are commercial flexibilities available, a deal still requires the NHS and an individual pharmaceutical company to come to an agreement on the appropriate price of a drug.
More information about the Accelerated Access Collaborative can be found here.
What is the Trust doing to help people obtain access for Trikafta? Is the Trust putting pressure directly on Vertex?
The Trust is engaging with UK health authorities and Vertex Pharmaceuticals to discuss the earliest possible routine access to the triple combination therapy. We are encouraging all parties to work collaboratively to achieve the best outcomes for people with cystic fibrosis by making new medicines available at the earliest opportunity.
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, on our website.
How will asking MPs to support your pledges help with this?
Asking your new MP to support the Trust’s pledges will enable us to build on our parliamentarian support network so that we can keep CF on the political agenda. Our pledges lay out how we want to see the future for people with CF and bringing politicians on that journey with us will enable us to call on their support when we most need it to overcome any hurdles we may face.
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 future clinical trials relevant to them, 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.
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.
When will the triple combination therapy be available on the NHS?
The triple combination therapy (elexacaftor, tezacaftor and ivacaftor, called Trikafta in the United States) is not currently licensed for use in Europe, and is currently being reviewed by the European Medicines Agency for safety. Our top priority is working with Vertex and the NHS to ensure the triple combination therapy is made available as soon as possible after licensing to people with cystic fibrosis.
What is the Cystic Fibrosis Trust doing?
The Cystic Fibrosis Trust is working closely with clinicians and Vertex to ensure that the compassionate use scheme for triple combination therapy is running efficiently and smoothly. Please speak to your CF clinical team for advice about eligibility for the scheme.