There is an urgent need for more effective treatments for MND. Researchers are focused on identifying more potential treatments for the disease and these are then tested in studies. The discovery and testing process is lengthy and it can take years for a new treatment to become routinely available to people in clinics. However, the number of studies testing these treatments is ever increasing and they are happening all over the world. With so many possible treatments being discovered and studied, it is hoped that research continues to drive us towards effective treatments for everyone with MND.
How do researchers find new drugs to test?
Researchers find new drugs to test through laboratory based research. Typically, they’ll use cells in a dish or animals (such as mice) to model aspects of the biology of the disease they are looking at. This means that the animals or cells are purposefully given a disease so that the researchers can study what happens in cells. Uncovering the biological changes that happen increases understanding of what’s going wrong in the body. If scientists can understand what changes are happening to cells during the disease, they may be able to find ways to stop or reverse them.
Scientists search for something that goes wrong in the disease which they believe can be corrected through therapies. This is what’s known as a therapeutic target. Once they have found a target, they investigate whether the changes can be corrected and how this might be done. This could involve testing drugs which already exist or creating a completely new drug to test.
When a target and potential drug have been found, researchers must do lots of testing in the lab in models of the disease. This is called pre-clinical testing and it’s purpose is to make sure that the drug isn’t harmful, targets and corrects what it was designed to and shows promise in models of disease. This testing is hugely important as it defines whether or not the drug is taken forward to clinical trials.
What are Clinical trials and why do we need them?
Potential new treatments for MND have to go through several stages of testing before we can determine if they are safe and effective for people with MND. These tests are called clinical trials and they assess the effects of possible new treatments in volunteers.
Clinical trials are used to test any new method for treatment and care, not just drug treatments. They can be used to test new forms of support (e.g. psychological, nutritional and respiratory support), cell and gene therapies, surgical procedures, medical devices and online resources designed to offer support and information about care. For the purposes of this blog we are focusing on drug trials, but the same concepts apply for whatever the trial is testing.
For drug trials, it is important that the trial determines if there are any negative side effects from the new treatment that may be more harmful than the disease it was designed to treat. It is also necessary to prove, beyond reasonable doubt, that the treatment is beneficial by monitoring the effects of the treatment in a group of people. Clinical trials remain the only way to know for sure that a treatment is safe and beneficial for people with the disease.
What happens in a clinical trial?
There are several different stages of testing in clinical trials and what happens during a trial depends on which stage or phase the trial is in. Most new drugs have to go through all of the phases before the drug is available to people with the disease, and this takes years. The details of each phase of clinical trials can be found below.
Phase 1 trials
Phase 1 studies are relatively small studies which look at the effects of taking the drug in a very small number of people, usually somewhere between 5 and 20 participants, for a few months. The main aim of this first phase is to assess the safety of the drug which includes monitoring any side effects or reactions to the drug. The participants in this phase might be healthy volunteers or might be people with MND. If the drug is found to have dangerous side effects or cause very harmful reactions, the trial is stopped and the drug will not continue to the next phase.
Phase 2 trials
In Phase 2 trials, the drug is tested in more people and for a longer period of time, typically several months to a couple of years. The participants may also be split into two groups; one who takes the drug and one who takes a dummy drug or placebo. This is so that the two groups can be compared to make sure that any effects are a result of taking the drug and not due to chance. Phase 2 trials aim to find the optimal dose of the drug, the best time to take the drug and determine if the drug is being delivered (e.g., by mouth, or injection) in the most appropriate way. These findings are then taken forward to be used in the next phase of the trial. Some phase 2 trials might also look at the drugs ability to treat the disease but this is only to give an indication of possible signs of benefit to help decide whether the drug should move on to the next phase. The numbers of participants in these trials are still too small to know for sure if the drug is going to be beneficial.
Phase 3 trials
Phase 3 trials run for a longer amount of time and look at the effects of the drug in a lot more people than phase 2 trials. They usually test the drug in hundreds of people with the disease to ensure that the results are reliable. The main aim of a phase 3 trial is to show whether the drug is beneficial for people with MND. Phase 3 trials nearly always have a placebo or control group to make sure that any benefits seen are due to taking the drug. If the drug is found to have a beneficial effect at the end of this phase, the company behind the drug might apply for the treatment to be licensed for the disease. If a treatment is licensed, it means that the information about the drug has been thoroughly assessed, and that the drug has officially been approved for prescription or sale for the disease that the trial looked at. The results from a phase 3 trial are essential for determining whether a drug is licensed to treat a disease.
Phase 4 trials
This phase of clinical trials happens after a drug has been licensed to treat the disease and assess the drug in a real-world situation rather than as part of a study. They usually include monitoring and gathering data from a very large number of people who are all taking the drug over a number of years. Phase 4 trials look at the long term benefits, side effects and safety of the treatment to make sure that it is still effective and safe to take over a longer period of time. If a drug is found not to be safe or effective in the long term, the drug license can be revoked, meaning that the treatment would be discontinued and no longer available for people to take.
Some exceptions to the rules…
While most clinical trials will follow through these different stages, not all of them will. Here we discuss some of the exceptions from the usual process.
Drug repurposing trials
Some clinical trials test drugs that are already known to be safe as they are approved to treat other diseases. It’s relatively common for a drug that was designed for one disease to have beneficial effects for other diseases. This is called drug repurposing. Drug repurposing shortens the clinical trial process as there is no need for a phase 1 study because the drug is already known to be safe. Some clinical trials in MND are drug repurposing trials testing if these drugs could be beneficial to people with MND.
Platform trials
Clinical trials are typically designed to test one potential treatment against a placebo and run for several years. In recent years, this traditional trial design has been adapted into platform trials. Platform trials test multiple drugs at the same time and are designed to run over many years, avoiding the expensive and time-consuming set up process for each trial. These trials randomly assign participants to one of several drugs being tested or a placebo group. Having one placebo group to compare all of the drugs to allows more participants to receive a drug whilst speeding up the process of finding an effective treatment. Platform trials are also adaptive which means that new drugs can be added throughout the trial and drugs which show no signs of benefit can be quickly removed. There are usually several ‘checkpoints’ built into the trial so that data collected so far can be assessed and a decision can be made by a committee as to whether to continue testing or remove the drug from the trial.
How is this linked to MND?
Clinical trials are the only way to know for sure whether a potential treatment is safe and effective for people with MND. More and more possible treatments are being discovered or created in laboratories and these need rigorous testing to prove that they are having an impact on the disease, before they can be considered for licensing and made available in clinics. Although the trials process can be lengthy and take several years to complete, they are a vital part of the process to bring new treatments to everyone with MND. You can find out more about clinical trials on our website.
In the previous blogs, we looked at biomarkers and some examples of markers being looked at for MND. In the next blog, we’ll delve into how biomarkers are being used in clinical trials to help build a clearer picture of whether the treatment being tested is effective at slowing the biology of the disease.
