​New hope for ultra-rare black bone disease as EU funded clinical trial ends

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.

Prof. Lakshminarayan Ranganath, DevelopAKUre’s Chief Investigator

The end of a five year clinical trial for AKU

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 £5 million 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.

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About alkaptonuria (AKU)
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AKU, or black bone disease, was the first identified inherited disease. A genetic mutation causes a build-up of a toxic acid that pigments and eventually destroys patients’ bones, cartilage and tissue, turning them black and brittle. Many life-changing disabilities result. Patients develop early-onset osteoarthritis, which can destroy every joint in the body.

​One patient said that "it feels as if your bones are wrapped in barbed wire". Heart disease can also start when tissue hardens around the heart. Because of all this, patients can suffer from chronic pain, depression and isolation. AKU affects approximately 1 in 500,000 people, apart from in Slovakia where it is more common and affects 1 in 19,000 people.

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About SONIA 2 
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The SONIA 2 trial took place in three clinical trial centres: the Royal Liverpool and Broadgreen University Hospitals NHS Trust in the UK, the Hôpital Necker-Enfants Malades in Paris, France, and the National Institute for Rheumatic Diseases in Piešťany, Slovakia. It followed a four-week dose finding study called SONIA 1 in 2013.

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About DevelopAKUre
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DevelopAKUre is an EU-wide consortium consisting of the following organisations: the AKU Society (UK), the University of Liverpool (UK), the University of Siena (Italy), the Biomedical Research Centre (Slovakia), the Royal Liverpool and Broadgreen University Hospitals NHS Trust (UK), Nordic Biosciences (Denmark), SOBI (Swedish Orphan Biovitrum, Sweden), PSR (The Netherlands), ALCAP (France), the National Institute of Rheumatic Diseases (Slovakia), Hôpital Necker (France), and the Institut Necker (France).

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About the AKU Society

The AKU Society was founded in 2003, when there was no licensed treatment for AKU. The society has pioneered an international clinical trial into a drug called nitisinone, which reduces the harmful effects of the disease.  It also offers support to AKU patients and their families. Patients receive home visits and get the latest information online. Specialised patient workshops, held twice a year, are a source of advice and support for patients in and outside the UK. Patient Ann Kerrigan said that ‘the peer to peer support has really made a difference for me, helping me feel less isolated.’

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