Monday, June 16, 2014

Cambridge, 16th June 2014 – Patients with a rare genetic disease are today starting on a major international clinical trial of a treatment that could dramatically change their lives for the better.

Run by the Royal Liverpool University Hospital and patient group the AKU Society, the five-year Phase III trial aims to recruit 140 patients to three centres across Europe, including one in Liverpool.

Alkaptonuria (AKU) is caused by a genetic defect that leads to bones and cartilage going brittle and black. It is often referred to as black bone disease. The trial will assess the long-term effectiveness of a potential drug called nitisinone in preventing the progression of the disease.

“All patients with alkaptonuria (AKU) are heavily motivated to participate in a trial that could change their lives,” said Dr Nicolas Sireau, Chairman of the Cambridge-based AKU Society and father of two children with AKU. “We have patients ready to start the trial, but if anyone believes someone in their family has the condition we urge them to get in contact with the AKU Society.”

The funding for the trial includes £4.8m from the European Commission, with another £3.2m in co-financing from a European consortium including 13 hospitals, pharmaceutical companies and consultancies, universities, biotech companies and national AKU patient groups.

Prof Lakshminarayan Ranganath, Medical Director of the AKU Society and Coordinator of the trial, said: “This is the first time patients, clinicians, scientists and industry have collaborated so closely on launching a major trial for such a rare genetic disease. We hope it will serve as a model for other groups trying to develop treatments for rare diseases.”

END

Notes to editors 

About alkaptonuria 
Alkaptonuria or AKU was the first genetic disease to be identified 110 years ago[i]. It is caused by a recessive gene on chromosome three leading to a deficiency of a key enzyme (HGD) that activates one of the steps in the breakdown of the amino acid tyrosine[ii]. The deficiency means that patients are unable to break down protein correctly. Homogentisic acid accumulates in body tissue, leading to the breakdown of cartilage, which becomes black and brittle[iii]. It affects one in every 250,000 people.

Damaged cartilage breaks away; causing early-onset osteoarthritis and joint destruction, which often leads to joint replacement surgery in middle age[iv].

The debilitating nature of the disease means that many patients are unable to work. Currently, there is no approved treatment for AKU, apart from painkillers and physiotherapy offered to combat pain. Many patients go on to need joint replacements for their damaged knees, hips and shoulders[v].

About the trial
SONIA 2, the Phase III clinical trial, will recruit patients to three centres in Europe: Liverpool, UK; Paris, France; and Piestany, Slovakia. More details of the trial can be found at www.developAKUre.eu.

Results of an earlier Phase II trial, which established the most effective dose for subsequent trials, will be published later this year.

About nitisinone 
Nitisinone has been found in early clinical trials to reduce homogentisic acid levels by 95%, resulting in patients reporting significantly reduced joint and back pain[vi]. Researchers believe that if nitisinone is administered early enough it could prevent the toxic acid from building upiv, allowing sufferers to lead a normal, pain-free life.

Nitisinone is licensed for the treatment of another metabolic disorder, tyrosinaemia type 1, and marketed as Orfadin® for tyrosinaemia type 1 by Swedish Orphan Biovitrum.

About the AKU Society 
The AKU Society was founded in 2003 in Liverpool by AKU sufferer Bob Gregory and his doctor, Dr Lakshminarayan Ranganath of the Royal Liverpool and Broadgreen University Hospitals. It was the first AKU charity in the world. It is patient-led and includes patients, relatives, medical experts and friends and carers among its supporters. The society offers people with AKU help and support, raises awareness of AKU and supports research into its treatment. Its vision is to find a cure for AKU within the next decade.

The AKU Society has established an influential multidisciplinary network, including representatives from numerous universities and hospitals, pharmaceutical companies and national AKU patient groups in Europe, the Middle East, Asia and North America. The society has also funded two research programmes into AKU and the first AKU information centre.

About clinical trials Medical trials are traditionally funded by large pharmaceutical companies. However, in recent years patient groups have become far more active within research and development, particularly within the United States. For example, the Michael J Fox Foundation’s (www.michaeljfox.org)goal is to speed progress within Parkinson’s therapeutic development. They are currently providing significant funding to the most promising research organisations.

For more information, please contact: Oliver Timmis
By e-mail: [email protected]
By phone: +44(0)7799 037726[i] Introne, W, L. et al. 2011. A 3-year randomised therapeutic trial of nitisinone in alkaptonuria. Molecular Genetics and Metabolism, 103, 207-314.[ii] Zatkova, A. 2011. An update on molecular genetics of alkaptonuria AKU. Journal of Inherited Metabolic Disorders, published online.[iii] Phornphutkul, C. et al. 2002. Natural history of alkaptonuria. The New England Journal of Medicine, 347(26), 2111- 2121.[iv] Ranganath, L., & Cox, T. 2011. Natural history of AKU revisited: analyses based on scoring systems. Journal of Inherited Metabolic Disorders, published online.[v] Suwannarat, P. 2005. Use of nitisinone in patients with alkaptonuria. Metabolism: Clinical and Experimental, 54, 719-728.[vi] Laxon, S., Ranganath, L., & Timmis O. 2011. A patients journey: Living with alkaptonuria. British Medical Journey, 343.