A ground-breaking clinical trial of a drug to treat the ultra-rare disease alkaptonuria (AKU) came to an end in January, with results expected in late 2019.
The drug, called nitisinone, prevents the build-up of an acid that attaches to joints and bones and turns them black and brittle, leading to severe pain and osteoarthritis.

The clinical trial – called SONIA 2 (Suitability Of Nitisinone In Alkaptonuria 2) – studied 138 AKU patients for five years to see whether the drug slows or even halts the progress of the disease. The last patient had their last visit on 18 January, marking the end of the clinical stage of SONIA 2.

Twelve organisations – under the name DevelopAKUre – implemented the SONIA 2 trial. It included hospitals, universities, patient groups, a small business, a biotech and a pharma company from seven countries of the European Union and was financed by a £5m grant from the European Commission.

Nitisinone is already used off-label at the National AKU Centre run by the Royal Liverpool and Broadgreen University Hospitals NHS Trust for English and Scottish patients. Published data from the National AKU Centre shows that nitisinone slows down the progress of the disease.

However, for nitisinone to receive a license from the European Medicines Agency it needs to be studied successfully through a randomised control trial on many patients – hence the importance of SONIA 2.

DevelopAKUre’s chief investigator, Prof Lakshminarayan Ranganath, said:

‘Despite AKU being first identified more than 100 years ago, patients still do not have a licensed therapy to treat the disease effectively. We hope that SONIA 2 will change this and provide the data needed for the European Medicines Agency to grant nitisinone a marketing authorisation for AKU.’

Jules West, operational director for research, development and innovation at the Royal Liverpool and Broadgreen University Hospitals NHS Trust, said:

‘We are very proud to reach this important milestone in helping to find new treatments for alkaptonuria. The work that our teams in Liverpool have done as part of DevelopAKUre’s clinical trial is another great example of the world-leading research being carried out at the trust.
‘Our involvement in this important research continues to highlight Liverpool’s pivotal status in life sciences. We look forward to hearing more about the results of SONIA 2 later this year.’

The coordinator of the clinical trial centre in Piešťany, Slovakia, and director of the National Institute of Rheumatic Diseases, Dr Richard Imrich, said:

‘The AKU clinical studies have so far been the most complex ones performed at our institute. Our team had to overcome a number of challenges, such as initially low patient willingness to participate in the study, a complex protocol of examinations, and many logistical problems recruiting patients from other EU countries and Jordan.’

The Chair and CEO of the AKU Society patient group, Dr Nick Sireau, said:

‘DevelopAKUre is an excellent example of collaboration on a European scale in order to treat an ultra-rare disease. Without the European Commission’s support, it is unlikely that we’d have been able to secure the level of funding needed to carry this out.’

‘But the journey is far from over. Even if the European Medicines Agency agrees to a marketing authorisation, the drug still needs to be approved by the national health reimbursement agencies in each EU country.’

A patient enrolled in the SONIA 2 clinical trial said:

‘AKU is such a rare genetic disease that I felt the obligation to help the researchers with everything I could. I have gained more knowledge about AKU.’