We recently attended an online webinar organised by Findacure and Healx, explaining the concept of drug repurposing. This is something that is very relevant to the AKU Society and our patients, as the drug we are currently trialling as a part of DevelopAKUre, nitisinone, is a repurposed drug. This week’s blog discusses drug repurposing and its benefits in treating rare diseases.

What is drug repurposing?

As Findacure defined, drug repurposing is “taking a drug intended to treat one patient population, and demonstrating its efficacy in the treatment of a completely different group of patients.” It’s using an existing drug and applying it in a second disease. Nitisinone is a good example of this.

Nitisinone was first licensed for tyrosinaemia type I (a serious disease that causes fatal liver tumours in young children).  However, there is evidence that nitisinone can also work to treat alkaptonuria, a completely different condition. Our clinical trials, DevelopAKUre, should prove if nitisinone is an effective treatment. If so, then once the trials have finished, and the results have been analysed, we’ll need to apply for another license for nitisinone as an approved treatment in AKU, improving access to the drug for all AKU patients.

Why is drug repurposing appropriate for other rare diseases?

There are 7000 rare disease, affecting 350 million people worldwide. Yet only 400 rare diseases have treatments. There’s a massive need for more research into providing treatments for the thousands of diseases that currently lack any hope of a cure. Findacure was founded to help solve this problem of a lack of treatments, and believe that drug repurposing could be a good means to achieve their goal.

Most pharmaceutical companies have a database of old drugs they have developed, but which were never licensed for use treating a specific disease. A large proportion of those drugs are safe to use in humans, but for example, were developed for a disease where there was another, existing, treatment. However, they could be useful for a second disease.

Mass screening allows researchers to quickly test hundreds of those drugs against a model of a disease. A disease model aims to represent a disease in a test tube. For example in AKU, we could apply nitisinone directly to the homogentisate dioxygenase enzyme (the enzyme which is not formed correctly in AKU patients and causes the disease). Therefore, it is possible to take a library of old drugs and test them in a disease model to see if any of them have a positive effect. If they do, then they can be studied further, eventually being tested in human patients.

Mass screening does have downsides though. Disease models may not accurately reflect the disease in humans – so what works in a model may not work in human patients. Models also simplify the way drugs interact with a human body. For example, in AKU, nitisinone is swallowed as a pill, and needs to find a route through the body to reach the liver (the ‘target’ organ when treating AKU). If a repurposed drug works in a disease model, it may still prove very difficult to administer in humans.

However, there are several big advantages of using drug repurposing in rare diseases. All candidate drugs will have a proven safety record, with many drugs having been using in human patients for several years. This means that the cost of investigating a repurposed drug is much cheaper than the cost of developing a new drug from scratch. The cost of new drugs has been steadily increasing in the last few decades, and since rare diseases have small patient populations, they are often considered as financially uninteresting for pharmaceutical companies. Drug repurposing offers an excellent compromise in cost, while still provided medications for the hundreds of currently untreated rare diseases.

To watch a recording of the webinar and to hear Findacure’s Dr Rick Thompson and Healx’s Dr David Cavalla explain drug repurposing and how their organisations can solve some of the issues such as funding projects and improving efficiency in finding new treatments, please see the video on Findacure’s YouTube page: https://www.youtube.com/watch?v=a9EQAoochEA.