EU/3/06/370

On 8 June 2006, orphan designation (EU/3/06/370) was granted by the European Commission to MGI Pharma Limited, United Kingdom, for decitabine for the treatment of acute myeloid leukaemia.
The sponsorship was transferred to Janssen-Cilag International NV, Belgium, in March 2007.

What is acute myeloid leukaemia?

Acute myeloid leukaemia is a disease in which cancer cells are found in the blood and the bone marrow. The bone marrow is the spongy tissue inside the large bones in the body. Normally, the bone marrow makes cells called “blasts” that mature into several different types of blood cells that have specific functions in the body. These include red cells, white cells and platelets. Red blood cells carry oxygen and other materials to all tissues of the body. White blood cells fight infection. Platelets make the blood clot. When leukaemia develops, the bone marrow produces large numbers of abnormal blood cells. There are several types of leukaemias. In myeloid leukaemia blasts that are developing into white blood cells called granulocytes are affected. The blasts do not mature and become too many. These blast cells are then found in the blood and also accumulate in the bone marrow. Leukaemia can be acute (when it develops quickly with many blasts). Acute myeloid leukaemia is life-threatening.

What are the methods of treatment available?

Treatment for leukaemia is complex and depends on a number of factors including the type of leukaemia, the extent of the disease and whether the leukaemia has been treated before. It also depends on the age, the symptoms, and the general health of the patient. The primary treatment of acute myeloid leukaemia is chemotherapy (using drugs to kill cancer cells). Several products were authorised for the condition in the Community at the time of submission of the application for orphan drug designation.

Decitabine might be of potential significant benefit for the treatment of acute myeloid leukaemia, because it may act in a different way than other medicines, which might potentially be easier to use in the older patient population. The assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

What is the estimated number of patients affected by the condition*?

According to the information provided by the sponsor, acute myeloid leukaemia was considered to affect less than 46,000 persons in the European Union.

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed based on data from the European Union (EU 25), Norway, Iceland and Lichtenstein. This represents a population of 59,700,000 (Eurostat 2004). This estimate is based on available information and calculations presented by the sponsor at the time of the application.

How is this medicinal product expected to act?

Decitabine is a chemical substance, which is related to cytidine. Cytidine is part of the fundamental genetic material of cells (DNA and RNA). Decitabine blocks (inhibits) the building up (synthesis) of DNA and thereby could inhibit the growth of tumour cells.

What is the stage of development of this medicinal product?

The effects of decitabine were evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials in patients with acute myeloid leukaemia were ongoing.
Decitabine was not authorised anywhere worldwide for acute myeloid leukaemia, at the time of submission. Orphan designation of decitabine was granted in the European Union and in the United States for treatment of myelodysplastic syndromes.
According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 5 April 2006 a positive opinion recommending the grant of the above-mentioned designation.

Opinions on orphan medicinal products designations are based on the following cumulative criteria:

• the seriousness of the condition, 
• the existence or not of alternative methods of diagnosis, prevention or treatment and 
• either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments.

Designated orphan medicinal products are still investigational products which were considered for designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of the quality, safety and efficacy will be necessary before this product can be granted a marketing authorisation.

During its meeting of 4-5 September 2012 the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/06/370 for Dacogen (decitabine) as an orphan medicinal product for the treatment of acute myeloid leukaemia. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other satisfactory methods of treatment. As other satisfactory methods of treatment for patients with this condition are authorised in the European Union (EU), the COMP also looked at the significant benefit of the product over existing treatments. The COMP recommended that the orphan designation of the medicine be maintained.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Dacogen for:

‘treatment of adult patients aged 65 years and above with newly diagnosed de novo and secondary acute myeloid leukaemia (AML), according to the World Health Organisation (WHO) classification, who are not candidates for standard induction chemotherapy’.

This falls within the scope of the product’s designated orphan indication, which is:’ acute myeloid leukaemia’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in June 2006. Acute myeloid leukaemia remains a condition that is a long-term debilitating and life-threatening disease because it reduces the patient’s ability to fight infections and causes bleeding in the gut and brain.

Prevalence of the condition

The sponsor provided updated information on the prevalence mainly derived from the database Globocan 2008. On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of acute myeloid leukaemia remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was estimated to be less than 2 people in 10,000. This is equivalent to a total of fewer than 101,000 people in the EU.

Existence of other satisfactory methods of treatment

At the time of the review of the orphan designation, other methods of treatment were authorised in the EU for the treatment of acute myeloid leukaemia. The main treatment was 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).

Significant benefit over existing treatments

The COMP concluded that the claim of a significant benefit of Dacogen in acute myeloid leukaemia is justified on the basis of improved effectiveness in a sub-group of patients aged 65 years and above with acute myeloid leukaemia who are not eligible for standard induction chemotherapy. This is based on the results from a clinical trial comparing Dacogen with either supportive care (any medicine or technique to help patients, excluding anticancer medicines or surgery) or low-dose cytarabine (another anticancer medicine) which showed an improvement in median survival of 2.7 months for Dacogen-treated patients.

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Dacogen is of significant benefit for patients affected by acute myeloid leukaemia.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Dacogen still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.