Research based candidate selection

A drug repurposing candidate can be identified based on experiences with patients (e.g. anecdotal evidence), or through ideas that have already been suggested within academia. As patient groups often have extensive networks in patient and academic communities, it is often possible for them to drive this process by collecting information through these connections.
Partnering with clinicians and academic scientists can then allow a patient group to progress the idea into the laboratory, to determine whether it is a suitable candidate. This requires a model system (e.g. a mouse model), on which the impact of the drug on a specific disease pathway can be measured.
The Alkaptonuria (AKU) Society’s mission to repurpose nitisinone for use in alkaptonuria is a great example of how a repurposing candidate can be selected. Nitisinone had previously been approved for the treatment of tyrosinemia type 1 which impacts the same biological pathway affected by alkaptonuria. The AKU Society identified a US trial for nitisinone that had failed due to poor endpoint selection, and decided to pursue it as a repurposing project. They then worked in collaboration with academics and clinicians to develop an AKU mouse model on which the drug could be tested, helping to ultimately confirm nitisinone as a suitable repurposing drug candidate. A specialist centre was then secured for AKU that could prescribe nitisinone off-label, and clinical trials were organised with the patent-holding pharmaceutical company and a contract research organisation, to assess its efficacy. Over 140 patients were recruited for the phase III study, which was completed in 2019 with positive results. The consortium are now looking to approach the European Medicines Agency (EMA) to secure marketing authorisation for nitisinone for the treatment of alkaptonuria.