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.
Once a new treatment has a license, drug appraisal bodies such as the National Institute for Health and Care Excellence (NICE) and the Scottish Medicines Consortium (SMC) weigh up the price a company has asked for against the clinical trial data. They then recommend whether the drug will be cost-effective for the NHS and the taxpayer.
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.
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)
The AAR was an influential government report that suggested changes to the way new drugs are appraised and negotiations over pricing conducted. The AAR was the subject of a debate held on behalf of the Trust at Westminster in December 2016, and the Government issued its response to the Review in November 2017. One of the main outcomes was to establish a new Strategic Commercial Unit within NHS England, which will aim to negotiate for fair and sustainable prices for new medicines. Take a look at our campaign timeline for more information on the work we have been doing over the last few years to promote access to medicines for people with cystic fibrosis.
A five-year pricing agreement making Orkambi and Symkevi available to eligible people with cystic fibrosis in Scotland has been secured following discussions between Vertex Pharmaceuticals and the Scottish Government.
Additionally, long-term, real-world data will be collected about the effect of these medicines. This data will then be analysed and submitted to the organisation responsible to advising the NHS in Scotland on use of the medicine, the Scottish Medicines Consortium (SMC).
Kalydeco, Symkevi, and Orkambi will be available under all current and future licensed indications. In other words, all three products will be available to all patients whose doctors agree would clinically benefit from these products. You can see who might be eligible for Symkevi and Orkambi further down this page.
Kalydeco is already provided on the NHS in England but only for some eligible patients. This agreement broadens access to all clinically eligible patients. You can see who might be eligible here.
To find out if you are able to access Orkambi, Symkevi or Kalydeco, please contact your CF team.
Some of the information in these FAQs has been taken from an official document produced by NHS England.
NHS England has announced that people with cystic fibrosis living in England who stand to benefit from life-saving drugs Orkambi, Symkevi and Kalydeco will receive them as part of a two-year managed access agreement with the manufacturer, Vertex Pharmaceuticals. This agreement means universal access for over half of the cystic fibrosis population these drugs work for. It has been hard won and getting to this stage will come as a huge relief for many.
There are 8,200 people with cystic fibrosis living in England according to the 2018 Registry report, and over 4,000 people will stand to benefit from these drugs. The drugs will be available under all current and future licensed indications. In other words, all three products will be available to all patients whose doctors agree would clinically benefit from these products.
Kalydeco is already provided on the NHS in England but only for some eligible patients. This agreement broadens access to all clinically eligible patients. Look at who is eligible for Kalydeco, Orkambi and Symkevi.
Clinicians will be able to begin prescribing these drugs within 30 days of the agreement announced on 24 October 2019. Not all patients will require a change in treatment straight away but will have access when they need it. Doctors will prioritise patients in most need, for example where the patient has no other treatment available, as it will be logistically difficult for all eligible patients to have their treatment reviewed immediately.
NHS England will be working with all clinicians in cystic fibrosis services to support review of treatment, so that patients will be reviewed as quickly as possible and treatments will be made available in hospitals and through homecare as happens now.
The agreement is for an interim period, in which data will be collected to inform a full NICE appraisal of Orkambi and Symkevi. This will inform a new agreement after this point.
Vertex Pharmaceuticals has also agreed a flexible contractual mechanism, which means that in all circumstances all three medicines will continue to be available following completion of the NICE appraisal.
NICE – the world-renowned body in England that reviews and recommends medicines for use on the NHS according to their clinical and cost effectiveness – has backed this agreement.
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.
Historically, both countries have followed the position of NHS England, and as part of the agreement there is a requirement that Vertex must make equivalent terms available to the NHS in Wales and Northern Ireland, should those jurisdictions wish to benefit from them.
On 29 October, Northern Ireland confirmed its intention to complete a deal with Vertex Pharmaceuticals to make life-saving drugs Orkambi and Symkevi available to eligible people with cystic fibrosis (CF) living in Northern Ireland. Richard Pengelly, Permanent Secretary of the Department of Health in Northern Ireland, announced on 12 November that a formal agreement with Vertex Pharmaceuticals will be finalised and signed in the very near future, and that clinicians will be able to begin prescribing the drugs to the first eligible patients within the next few weeks.
On 13 November, the Welsh Minister for Health and Social Services, Vaughan Gething, announced that the Welsh Government has agreed terms in principle with Vertex Pharmaceuticals to make Orkambi and Symkevi available alongside Kalydeco in Wales. We await further confirmation on the details of this deal but understand that the Government aims to have it finalised by the end of November and intends to begin to roll out access where clinically appropriate to eligible patients the following month.
What is precision medicine?
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.
Ivacaftor (Kalydeco) is available on the NHS in the UK. It is available for everyone over the age of 12 months with one of nine rare gating mutations (G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P or G139D), and to people aged 18 years and older who have the R117H mutation.
Find out more about Kalydeco.
What does Kalydeco do?
Kalydeco helps open the ‘gate’ in the cells of people with CF, allowing chloride molecules to move in and out of the cells, and keep the balance of salt and water in the lungs. Drug companies sometimes refer to Kalydeco as a ‘potentiator’, for more information on what this means, see below.
Orkambi is what’s known as a double-combination therapy – it combines ivacaftor with another compound called lumacaftor. Orkambi works for people with two copies of the F508del mutation – around 50% of people with CF in the UK – and is licenced for those aged two years and over.
Orkambi is available on the NHS in Scotland as part of a five-year deal and on the NHS in England as part of a two-year deal. However, it is still not routinely available for use in Northern Ireland and Wales, and is only available on compassionate grounds, where the manufacturer provides it to individuals on a case-by-case basis, who fulfil a number of criteria. Find out more about Orkambi.
What does Orkambi do?
Orkambi has been shown to slow lung decline – the main cause of death in CF – by 42%, and to reduce the number of nasty chest infections which require inpatient hospital care to treat.
Symkevi is a double-combination therapy, licensed by the EMA on 1 November 2018 for those aged 12 and over with two copies of F508del or one F508del and one of 14 residual function mutations: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272 26A→G, and 3849+10kbC→T. The therapy comprises the compound combination tezacaftor/ivacaftor taken with additional ivacaftor.
Symkevi is available on the NHS in Scotland as part of a five-year deal, and on the NHS in England as part of a two-year deal. However, it is still not routinely available for use in Northern Ireland and Wales, and is only available on compassionate grounds, where the manufacturer provides it to individuals on a case-by-case basis, who fulfil a number of criteria. Find out more about Symkevi.
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.
The triple combination therapy (brand name Trikafta in the United States) uses a combination of ivacaftor, tezacaftor and elexacaftor, and could work in people with one copy of the F508del mutation and one copy of a 'minimal function mutation' - approximately 90% of the CF population. Recently, Trikafta was approved in the United States for those aged 12 and over who have at least one F508del mutation. Vertex have submitted Trikafta to the EMA, who decided in October that the drug would be reviewed under accelerated assessment. Because it has the potential to address an unmet need, it will be fast-tracked to reach a decision sooner, typically in seven to eight months, instead of the usual one year.
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.