The DevelopAKUre programme was a series of major international clinical trials, run by a consortium of 12 European partners. It aimed to study a drug, called nitisinone, and assess its effectiveness in treating AKU. Nitisinone is not licensed for AKU but has been used by many patients off-label and at the National Alkaptonuria Centre (NAC) in Liverpool. Those patients benefit, but the only way to be sure a drug works is through clinical research.

The DevelopAKUre clinical trials finished in 2019 and successfully showed that nitisinone lowered the amount of homogentisic acid (HGA), the acid that causes the damage in AKU, by 99%. Sobi, who makes the drug, has applied to the European Medicines Agency (EMA)for a license for its use in AKU across Europe. We anticipate to hear their decision by the end of 2020.

DevelopAKure Project board final meeting in Seina

• SONIA 1 (Suitability of Nitisinone In Alkaptonuria 1) was designed to ascertain the correct, and most effective, amount of nitisinone patients should take to reduce levels of HGA – this is called dosage. SONIA 1 finished In June 2014 and the main scientific paper was published in December 2014. It found that levels of HGA are reduced by nitisinone and that this is dependent on dosage levels.

• SONIA 2 (Suitability of Nitisinone In Alkaptonuria 2) was designed to test the safety of nitisinone and whether it slowed down the damage HGA does to the body of AKU patients. SONIA 2 recruited 138 patients over three trial sites in Liverpool, UK; Paris, France and Piešťany, Slovakia. The trial took place over four years and required patients to make up to 6 trips to their nearest trial site. The patients were split into two groups of 69 with one group taking nitisinone and one not taking nitisinone. This was important as it allowed us to show the positive effect of nitisinone. SONIA 2 finished in 2019.

• SOFIA (Subclinical Ochronotic Features in Alkaptonuria) was designed to compare AKU patients from different age groups to study when symptoms start to present. The study was designed to enable us to understand at what age AKU patients need to start taking nitisinone to best combat the damaging effects of the disease. SOFIA tested patients for ochronosis, the process where cartilage is discoloured black by the effects of AKU. This is thought to be the earliest sign of the more damaging symptoms of AKU. SOFIA recruited 30 patients from a range of 7 age groups from 16 to 50+. The study required one visit to the Royal Liverpool University Hospital. SOFIA highlighted ochronosis in patients as young as 16 and underlined the need for a study into children under 16.