This medicine is now known as guadecitabine.
On 14 December 2015, orphan designation (EU/3/15/1597) was granted by the European Commission to Otsuka Pharmaceutical Europe Ltd, United Kingdom, for sodium (2R,3S,5R)-5-(4-amino-2-oxo-1,3,5-triazin-1(2H)-yl)-2-(hydroxymethyl)tetrahydrofuran-3-yl ((2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9(6H)-yl)-3-hydroxytetrahydrofuran-2-yl)methyl phosphate for the treatment of acute myeloid leukaemia.
The sponsorship was transferred to Otsuka Pharmaceutical Netherlands B.V., Netherlands, in March 2019.
Please note that this product was withdrawn from the Union Register of orphan medicinal products in November 2020 on request of the Sponsor.
Acute myeloid leukaemia (AML) is a cancer of the white blood cells (cells that fight against infections). In patients with AML, the bone marrow (the spongy tissue inside the large bones, where blood cells are produced) produces large numbers of abnormal, immature white blood cells. These abnormal cells quickly build up in large numbers in the bone marrow and are found in the blood.
AML is a long-term debilitating and life-threatening disease because these abnormal immature cells take the place of the normal blood cells, causing bleeding episodes, blood clots and reducing the patient's ability to fight infections.
At the time of designation, AML affected approximately 1.5 in 10,000 people in the European Union (EU). This was equivalent to a total of around 77,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).
* Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 28), Norway, Iceland and Liechtenstein. This represents a population of 512,900,000 (Eurostat 2015).
Treatment for AML is complex and depends on a number of factors including the extent of the disease, whether it has been treated before, and the patient's age, symptoms and general state of health. At the time of designation, the main treatments for AML were chemotherapy (medicines to treat cancer) and haematopoietic (blood) stem-cell transplantation (a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow).
The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with AML because early results from studies show that it might produce a response in patients whose disease has come back after other treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
The medicine consists of an approved leukaemia medicine, decitabine, which has been linked to a substance called deoxyguanosine. When the medicine is injected, decitabine is slowly released from the medicine by enzymes in the body, giving it a prolonged action. The released decitabine becomes incorporated into the DNA (genetic material) of the cell. This blocks the activity of enzymes called DNA methyltransferases (DNMTs), which are responsible for promoting the development and progression of cancer. By blocking DNMTs, decitabine will block the division of the leukaemia cells and lead to their death.
The effects of this medicine have been evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with AML were ongoing.
At the time of submission, the medicine was not authorised anywhere in the EU for AML. Orphan designation of the medicine has been granted in the United States for this condition.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 November 2015 recommending the granting of this designation.
Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.
Otsuka Pharmaceutical Netherlands B.V.
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: