Making the RARE voice heard
Alkaptonuria (AKU) is a destructive genetic disease. Due to a rare genetic mutation, the human body is unable to break down an amino acid called tyrosine, contained in the protein that we eat. As a result, a toxic acid – homogentisic acid – builds up in the blood. This attacks bones, cartilage and tissue, making them black and brittle. Early onset osteoarthritis can destroy every joint in the body. Patients can also suffer from prostate stones and aortic valve disease. It is estimated that one in 250,000 people worldwide suffer from the disease.
AKU was first identified as an inherited disease in 1902. When the AKU Society was founded in 2003, there was still no proven effective treatment. However, many patients use a drug called nitisinone on an ‘off-label’ basis. (In other words, they take an unlicensed drug because they believe it has positive effects.) In the mid-2000s, the National Institutes of Health organised trials in the USA. Though patients reported that nitisinone helped them, the trials failed. Too few patients were recruited and the criterion for success was not precise.
In 2012, the AKU Society spearheaded an international consortium called DevelopAKUre to organise new clinical trials. DevelopAKUre involves three clinical sites (the Royal Liverpool University Hospital, the National Institute of Rheumatic Disease in Piešt’any, Slovakia, and Paris’ Hôpital Necker), as well as researchers from the Universities of Liverpool and Siena, the biotech Nordic Bioscience and Bratislava’s Biomedical Research Centre. In addition the consortium includes the pharmaceutical company Sobi, which supplies nitisinone for the trial, clinical trial experts from a company called PSR Group, and our French sister society ALCAP. Together, we raised six million euros from the European Commission’s FP7 programme and received five million euros in co-financing.
We believe that this is the first time that a British patient group like the AKU Society has been the driving force behind international drug trials. With regulations restricting contact between pharmaceutical companies and patients, patient groups can play a key role in the success of clinical trial design, recruitment and retention, helping to ensure patient needs are met. We have built relationships with and between AKU patients across Europe through our existing social media channels and through the online forum RareConnect.
According to Datamonitor, 90% of clinical trials are delayed because it is difficult to recruit patients.[i] The AKU Society handled patient recruitment for DevelopAKUre. Through an online advertising campaign, presentations at scientific conferences and an email to 7,000 specialist doctors, we managed to recruit half of the known European AKU patient population for the trials. We are equally proud of our retention rate. Of the 138 patients who started our current clinical trial in 2015, 125 are still on board.
Our first trial, SONIA (Suitability of Nitisinone in Alkaptonuria) 1, lasted for four weeks in 2013. Forty patients took part. Over the course of the trial, which was held in Liverpool and Piešt’any, we were able to effectively calculate the optimum dose of nitisinone which most reduced homogentisic acid in the blood. We are now using this dose for our current clinical trial, SONIA 2. Held in all three clinical sites, this trial started in 2015 and is due to finish in January 2019. By comparing the progress of AKU in patients on nitisinone with an untreated control group, we want to find out if nitisinone can slow or stop the damage caused by the disease. If successful, we shall apply for marketing authorisation from the European Medicines Agency. This will allow nitisinone to be marketed in Europe for use in AKU.
AKU Society also runs an observational study, SOFIA (Subclinical Ochronotic Features in Alkaptonuria). This ran in 2017 and was intended to work out the age at which AKU symptoms begin. A paediatric observational study is in the pipeline too where we would hope to discover when - or if - children should start taking nitisinone.
Meanwhile, the AKU Society has been in charge of dissemination for the DevelopAKUre trials. Our funding requires that we promote the trials as widely as possible. By taking the lead on dissemination, we also get the chance to meet new partners with new ideas. In addition to our main website, we maintain the DevelopAKUre microsite, this is full of information about the consortium and is regularly updated with current news. Patients are also alerted via email about major developments as they occur.
Finally, we continue to raise awareness for DevelopAKUre at major international conferences. Just this year, we have been to the Global Orphan Drugs Congress Europe, the Annual International Medical Students Meeting, the Royal College of Nursing Congress, the Osteoarthritis Research Society International World Congress and the European Conference on Rare Diseases.
If you would like to find out more about the AKU Society presenting DevelopAKUre at a conference/event, please contact:
Reece Edmends at firstname.lastname@example.org
 ‘Online recruitment is streamlining clinical trials’, Datamonitor, July 2008