The journey of a drug – what it takes to be approved

Each year, the MND Association dedicates the month of June to raising MND awareness. This year, we focus on the eyes – in most people with MND the only part of their body they can still move and the only way left for them to communicate. Alongside the Association-wide campaign, the Research Development team selected six most-enquired about topics, which we will address through six dedicated blogs.

So far, there is no cure for MND. In the past 22 years, we have only seen approval of two drugs that were either shown to prolong the life of MND patients by several months (riluzole in 1995 in the US) or to slow down symptom progression (edaravone in 2015 in Japan). It is only reasonable that you might wonder ‘what is taking so long?’ or ‘why are there not more drugs available?’.

It is very competitive in the world of medicinal drugs. From thousands of chemical compounds that are gradually eliminated as they go through different stages of drug development, only one makes it near the finish line. This line represents approval for marketing authorisation and there is no guarantee that this ‘top compound’ will actually make it to the end. So let’s have a closer look at the individual stages that a potential drug has to go through in order to be crowned the champion.

‘Creating the contestants’ – Research & Development

Before we can test effectiveness of any drug, we first need to know how a disease is causing disorder in the body. In MND, this can for example be surplus of chemical messenger glutamate, or build-up of toxic waste within motor neurons. Once a focus on one cause has been established, researchers can start looking for all possibly-suitable compounds that might revert or stop the negative process.

The compounds can either be engineered from scratch, developed from living or synthetic materials, or selected from a large library of already-known compounds. The research team then narrows down the number of compounds that are eligible for the specific disease and cause. Only the best of the best are then selected for further evaluation and, usually, their chemical structure is altered to be even safer and more effective. Therefore, only some compounds are eligible to enter a specific competition (eg aiming to decrease glutamate levels) and the process of selecting the primary candidates usually takes around 4 years.

‘The first test’ – Preclinical research

This next stage represents the first real test for the selected few drugs – they have to undergo a number of observations in a living cell in a laboratory dish (in vitro) or in a living organism – this is usually in animals, such as fruitfly or mice (in vivo). The researchers observe how the specific drug works within the cell and organism and look out for potential side effects. This is a very competitive stage as only the most promising drugs will be selected to continue to the clinical trials phase.

‘The Championships’ – Clinical trials

Now this is the bit that most people are familiar with – this is where we actually see the strength and weaknesses of the drug in real settings. It is just like watching elite athletes showing off their relentlessly-practiced skills at the World Championships. The clinical trials stage takes the drugs that successfully passed the preclinical stage and test how they work in humans (with or without the specific disease). Throughout a series of phases, researchers observe the drug’s safety (phase I), optimal dosage and short-term side effects (phase II), and effectiveness on stopping/slowing down the disease progression (phase III). Overall, only about 21% of drugs that make it into the clinical trials stage continue to phase III. If everything runs smoothly, the whole process of clinical testing can take up to 7 years.

‘Crowning the champion?’ – Authorisation review

If clinical trials show that a drug is safe to use and that it has statistically significant beneficial effect to the patients, the company who sponsored the clinical trials files an application for marketing authorisation (this is FDA in the USA and EMA in the EU). Only about 25% of drugs that made it into the final clinical trial phase apply for the authorisation.

Once filed, the whole series of studies from drug development to clinical trials – the drug’s performance throughout the competition – is reviewed by scientists, physicians and statisticians at the relevant authorisation agency. If they agree that the drug is safe and that its benefits outweigh any possible negative effects, then we have a WINNER!

The drug is now approved and a manufacturer can start producing it in larger quantities. Depending on each country’s regulations and healthcare system, additional approvals might be needed to be allowed to use the drug in that country or to offer the drug free of charge.

You can see that it is not a very easy and straightforward process and it takes a long time to come from the initial stages all the way to the end. However, hundreds of dedicated researchers are working hard every day to give new drugs a chance to shine and to also give hope that one day, we will have a world free from MND.