SONIA 2: Results of 1-year analysis

The DevelopAKUre Consortium is delighted to announce that they are now able to publish the results of the SONIA 2 1- year analysis. To read the translated Slovak page please click here/ Ak chcete čítať preložené slovenské stránky nájdete tu. To read the translated French page please click here / Pour lire la page française traduite, cliquez ici

All SONIA 2 patients have received a letter, written by Chief Investigator Prof Ranganath, that takes patients through the effect on HGA and conclusions that have been made. This letter is now being made available to all those who may be interested in the findings. If you would like any more information about the information below, or would like more information about AKU, please contact Ciarán Scott, Clinical Trials Officer at the AKU Society on

SONIA 2 is a 4-year efficacy and safety study, designed to collect evidence on whether nitisinone can be used in the treatment of AKU. Patients who enter the study are split into two groups, one group receiving 10 mg of nitisinone daily, and another group not taking nitisinone. The diagram below shows the two different study groups. All study patients have now completed at least one year of the study and we have analysed some of the results in order to verify a continued effect of nitisinone on HGA (see below) and to look at the safety data collected so far. Due to the slow progression of the disease, the final analysis of nitisinone´s clinical effect on AKU symptoms will take place as planned after 4 years



1) Effect on HGA

Nitisinone acts to reduce the formation of HGA (homogentisic acid), which is the chemical that causes damage in AKU patients. Therefore, the main analysis for the trial looks at the reduction of HGA excreted in the urine. We are also measuring the concentration of HGA in the blood (known as serum HGA).
For patients who are treated with nitisinone, HGA excreted in the urine decreased by on average 99.5% and the decrease in the blood was 97.5% after one year. The effect did not change from the 3-month to the 12-month visit. Thus, the study so far shows that the HGA-lowering effect of nitisinone remains as long as treatment continues. The table at the end of this letter presents the actual HGA concentration numbers if you are interested in looking more closely at this.

2) Safety

Treatment with nitisinone leads to increased concentrations of tyrosine in the blood, as we expected. This may cause eye complications such as eye pain or blurred vision. After one year of treatment, nitisinone has been temporarily withdrawn in 5 patients, due to such eye problems most likely caused by the increase of tyrosine. All patients recovered after stopping taking nitisinone, and have thereafter continued on a lower dose (2 mg daily), and a reduced protein diet. 
During the first year of the study, adverse events (i.e., any kind of health issues) were reported for 78 of the 138 (56.5%) patients participating in SONIA 2 (treated and untreated). Very few of these events, mostly those related to the eyes, were considered by the investigators to possibly be related to nitisinone. Most of the serious adverse events were due to medical issues commonly seen in AKU patients regardless of any treatment, and none of these were considered related to nitisinone. An adverse event is classified as serious if it results in hospitalisation, and examples of such events in SONIA 2 are joint replacements, fractures, etc. 
Nitisinone was generally found to be safe and well tolerated in SONIA 2 following one year of treatment.  As expected, the only safety concern related to nitisinone, was the elevated tyrosine levels affecting the eye. These eye effects all resolved upon stopping nitisinone. No patient on the reduced dose of nitisinone has had to withdraw from the study to date.


In summary, SONIA 2 one year study data shows that nitisinone treatment of AKU patients results in a significant reduction of HGA in the urine and blood with no safety concerns. To investigate the longer term effect of nitisinone in AKU disease progression, the study will now continue as planned and finish in March 2019.  Your continued participation in the study is very important, whether you are in the group receiving treatment or in the untreated group. 4-year data from as many patients as possible are needed to understand the effect of nitisinone on all the clinical measures that are studied in SONIA 2. 

Summary of HGA results:

This is a summary of the average HGA amounts excreted in urine, and the average concentrations measured in serum (blood), in patients before and after one year in SONIA 2.


SONIA 1 was completed in June 2014. The main scientific paper from the study was published in December 2014 in the Annals of Rheumatic Diseases. The paper is available online here but requires a subscription to view.  

Ultimately, the importance of SONIA 1 was to show evidence that nitisinone reduces HGA, and to choose the best dose to take forward into SONIA 2 (our current clinical trial).

SONIA 1 concluded that treatment with nitisinone in AKU patients does reduce HGA, and the reduction is dependent on dose. This means a larger dose of nitisinone results in a greater reduction of HGA.

The trial helped us to understand that 10 mg of nitisinone is the best dose to test the drug’s effectiveness in AKU patients. This is now the dose we are using for SONIA 2.

Prof Jim Gallagher from the University of Liverpool said “This is an outstanding example of impact in translational research, involving collaboration between clinical and basic scientists, patient organisations and pharma. Initially we demonstrated that nitisinone was completely effective and safe in AKU mice. We have now shown that it is an effective HGA-lowering therapy in AKU patients.”

While the study didn’t look especially at safety, there were no safety concerns at all during SONIA 1.



Welcome To DevelopAKUre

DevelopAKUre is a series of major international clinical trials, run by a consortium of 12 European partners. It aims to study a potential new drug, called nitisinone, and assess its potential effectiveness in treating the rare disease, alkaptonuria (AKU).

DevelopAKUre is co-funded by a grant from the European Commission. This website is run by a UK patient group, the AKU Society. Learn more about AKU on the AKU Society's What is AKU page.


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