The science behind access to EB treatments
To ensure that any treatments prescribed for epidermolysis bullosa (EB) are safe and effective there is a lengthy process, involving scientific research and government regulation. This is vital for people to experience good results from treatments and for there to be confidence and trust in UK medicine.
Find out more about the science behind access to EB treatments below or download our leaflet.
Scientific research is a series of processes that aim to override natural human biases and gut feelings to provide objective information and knowledge to everyone. It is critical to find out what causes EB symptoms and what can help to treat them.
Scientific research begins with an observation, seeing something happen and recording it, then counting and comparing how often it happens under different situations. If a baby is born with blistered skin, this symptom is an observation. Some researchers will study how often it happens, when, where, and how. The observations and analysis lead researchers to consider what causes the symptom and how it can be treated.
Scientists may use specialist techniques and equipment to look more deeply at the cells and proteins that make up human bodies. The things they count and compare help provide scientific evidence to support their ideas about causes of EB symptoms and potential treatments.
Scientific research is expensive and funding is provided by charities, the government (taxpayers) and private companies.
When researchers discover something, they write an article for publication in a scientific journal, so the knowledge becomes available to everyone. They don’t just say what they think they’ve found out, but explain clearly what they did, what the results were, and how they were analysed. This allows other researchers to draw their own conclusions and carry out further research to build on the new information rather than just believing what they are being told.
The editor of the scientific journal will arrange for other experts to check the article for mistakes, missing information or conclusions that don’t match the results, before it is published. This is called ‘peer review’ and helps to reduce the risk that mistakes could be shared. If the editor finds the research to be misleading, they can refuse to publish it. If a mistake is later discovered and pointed out, the journal editor may withdraw the article from their publication. All published scientific articles on EB can be accessed through the PubMed database.
Many research studies will have shortcomings, and some will provide stronger evidence than others, so it’s important that everyone can read exactly what was done. Transparency and questioning are part of the scientific process. Studies that show that a treatment does not work well, and should no longer be pursued, are just as important as those that show a treatment is effective for people to receive the best care.
EB is classified as a rare condition because it affects fewer than 1 in 2000 people (0.05%). There are thousands of different rare conditions and more than 1 in 20 people (5%) will be affected by one of them, but there are additional challenges to researching and approving treatments for rare conditions:
- Fewer people are living with EB so there are fewer people to take part in clinical trials, and they may live far away from each other and from places where research is carried out.
- There is less awareness and understanding of EB, the different EB types, how each type progresses and what treatments are needed, than for more common conditions.
- Fewer researchers are funded to dedicate their learning and expertise to EB than more common conditions.
- Pharmaceutical companies are less likely to get back the initial cost of developing a new treatment when there are only a small number of people who will buy and use the treatment.
The challenges of developing treatments for rare conditions:
Developing a new treatment (de novo) can take many years and cost hundreds of millions of pounds, or more.
The early stages of laboratory research, sometimes called ‘basic research’, that help to understand the causes of symptoms can take decades before a potential treatment can be created. Potential new treatments must then undergo rigorous tests in cell (in vitro) and animal (in vivo) models of EB before they are ever given to people in clinical trials. This is called ‘pre-clinical research’ and provides evidence that clinical trials should be funded.
A drug that is being given to people must be manufactured under highly regulated conditions called Good Manufacturing Practice (GMP). This is to ensure that there’s the same amount of the drug in each dose, that it’s carefully prepared to avoid contamination with other substances, and that it is packaged and labelled correctly for use. In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) regulates the production of drugs.
Clinical trials are first carried out in healthy people to determine a dose that doesn’t cause too many additional unwanted symptoms (side effects). After these phase 1 clinical trials, the established dose can be given to people living with EB in phase 2 and phase 3 clinical trials to test whether it improves their symptoms.
The plan of what will be done in a clinical trial should be published at the outset. At the end of the clinical trial, the method of testing and counting and comparing the outcomes must be published. The published results can then be used by the manufacturer of the treatment as evidence of its safety and how well it improves symptoms (effectiveness). The manufacturer must have enough good scientific evidence to gain regulatory approval from the MHRA which then provides a license for the treatment to be prescribed at specific doses for defined conditions.
Gene therapy treatments could be developed to treat the underlying genetic cause of EB rather than the symptoms. A genetic treatment might be specific to one genetic change or one gene only, but each therapy must be tested rigorously to prove its safety and effectiveness no matter how few people could be helped by it. For individualised treatments that use one person’s own cells to make a treatment solely for them, the process itself can be tested in a group of people to provide scientific evidence that it is a safe and effective treatment process.
After a clinical trial has shown that a new drug is safe and effective, it must be granted a license before it can be made available for widespread use. The license (Marketing Authorisation) confirms who can be treated, for which health condition(s), the dose and method of treatment.
Licenses are granted by the MHRA in the UK, by the European Commission, acting on advice from the European Medicines Agency (EMA) in Europe and by the Food and Drug Administration (FDA) in America. These bodies consider all the published evidence to ensure that the drug is safe and effective. The license provides confidence that the drugs that are available will help rather than harm those who use them.
Access to treatments
Because different countries have different processes, treatments can be available in some countries but not in others. When a treatment has a license from the MHRA that confirms it is safe and effective, it can be made available in the UK to buy privately at a price set by the pharmaceutical company that manufactures it. The National Institute for Health and Care Excellence (NICE) can then assess the evidence that the treatment is needed, its effectiveness, and the cost of paying to provide it fairly (equitably) to people living across the UK.
Patient testimony, describing the challenges of living with EB can be gathered from members of DEBRA UK and provided to NICE at this stage to support the need for a treatment. NICE may then recommend that the treatment should be funded by the National Health Service (NHS) and define which type(s) of EB and/or which symptoms it should be used for. The treatment should be available through the NHS within.
A drug that has not been licensed for use cannot be prescribed. However, prescribing a licensed drug for a condition not specified in its license is possible. Unlicensed use means that there is a recommended dosage, and the side effects of a drug are known, but that it may not have been fully evaluated in a new condition it is used to treat.
There are drugs already available within the NHS, licensed for other inflammatory skin conditions such as psoriasis and eczema but not EB, that could potentially improve EB symptoms. People desperate to alleviate EB symptoms, where there are currently no specific treatments, may be keen to just try whatever might help. However, without the evidence that these existing drugs truly are effective for the treatment of EB, people could end up trying out drugs, paid for by the NHS, that do more harm than good or do nothing at all.
Even if the drug did work brilliantly for one person, without this being counted and compared and reported and published, it would not provide evidence to help other people access it. These drugs need to be tested for people living with EB in drug repurposing clinical trials.
Drug repurposing
Drug repurposing involves using an existing drug that already has a license for one condition to treat another condition. It can also apply to using an existing licensed drug in a different dose or form to that specified in the license. Drug repurposing means that phase 1 clinical trials are not necessary as the dosing and side effects are already known. This makes drug repurposing a much quicker and cheaper route to securing effective drug treatments for people with all types of EB.
It is essential that drug repurposing clinical trials are carried out, so that working treatments can be made available fairly to everyone living with EB in the UK.
The DEBRA UK EB research strategy prioritises investment in drug repurposing to secure life-changing treatments for every type of EB as quickly as possible.