How are drugs appraised?
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). The AWMSG follows all NICE advice but if NICE is not due to assess a medication within 12 months of it getting a licence, AWMSG may run its own appraisal.
- Northern Ireland – NICE/Department of Health and Social Care (DHSC). The DHSC endorses NICE recommendations following local review by Northern Irish commissioners.
- 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.
The Scottish Medicine Consortium (SMC) is an independent advisory body that assesses and provides recommendations for use for all new medicines for NHS Scotland. It evaluates the clinical- and cost-effectiveness of new medicines by analysing available evidence, such as clinical trial data, patient and clinical views and financial considerations. It is the Scottish equivalent of the National Institute for Health and Care Excellence (NICE), which serves NHS England, and the All Wales Medicines Strategy Group (AWMSG) for NHS Wales.
A five-year pricing agreement make 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).
When the SMC appraised Orkambi in 2016, and Orkambi and Symkevi in 2019, it recommended against routine use of these medicines by the NHS in Scotland. The SMC said that there were uncertainties in the data provided by the drug company, Vertex Pharmaceuticals, and the cost could not be justified. There can be uncertainty in data for several reasons:
- Data on too few people
- Data collected over too short a time period
- Missing information
This agreement will allow the NHS in Scotland to prescribe effective medicines to people who stand to benefit from them, while data are collected to address the uncertainties, allowing for a resubmission by the drug company to the SMC within the agreement period.
The Cystic Fibrosis Trust has campaigned for this approach for four years. We have been arguing that the UK CF Registry can support managed access to new CF drugs across the UK since 2015. You can read our proposal here.
Further information can be found on our campaigning pages on our website. You can also contact the public affairs team at firstname.lastname@example.org.
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.
What is Kalydeco?
At the moment, ivacaftor (Kalydeco) is the only precision medicine available on the NHS in the UK. It is available for everyone over the age of two with one of nine rare gating mutations (G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P or G139D). 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.
What is Orkambi?
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 licensed by the EMA and in September 2019 was made available on the NHS in Scotland as part of a five-year deal. However, it is still not routinely available for use throughout the rest of the UK, 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 was made available on the NHS in Scotland in September 2019, as part of a five-year deal. However, it is still not routinely available for use throughout the rest of the UK, and is only available on compassionate grounds.
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.
A triple therapy from Vertex began Phase III clinical trials in March 2018, a therapy using a new compound, elexacaftor, with tezacaftor and ivacaftor. CFTR correctors Elexacaftor and tezacaftor are used to get the defective CFTR protein channels to the surface of the cell and ivacaftor, a potentiator, helps the channels to open and function more effectively.
This therapy has been submitted to the FDA in the USA by Vertex for priority review.
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.
Why are we still waiting for access to Orkambi and Symkevi?
It has been almost four years since the EMA licensed Orkambi for use by people with CF over the age of two with two copies of F508del, and a year since Symkevi was licensed for people aged 12 and over with two copies of F508del or one copy of F508del plus one residual function mutation. In September 2019 the drug’s manufacturer, Vertex, agreed a deal with the Scottish Government to provide these drugs to the 350 people with cystic fibrosis in Scotland who can benefit from them on the NHS in a five-year deal utilising data from the UK CF Registry. Talks in England, Wales and Northern Ireland continue, and it is hoped that the positive decision in Scotland will soon be reflected across the rest of the UK.
To find out whether you or your child might be eligible for a precision medicine, whether in Scotland or through compassionate use, please speak to your CF team.