EU/3/00/005:

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. These blasts do not mature but multiply abnormally and accumulate in the bone marrow. Then they are also found in the blood. Leukaemia can be acute (when it develops quickly with many blasts). Acute myeloid leukaemia is life-threatening.

At the time of designation, acute myeloid leukaemia affected not more than 0.66 in 10,000 people in the European Union (EU). This was equivalent to a total of not more than 25,000 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. At the time of designation, this represented a population of 375,500,000 (Eurostat 2000).

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 leukemia 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. Gemtuzumab ozogamicin, also known as Mylotarg, could be of potential significant benefit for the treatment of acute myeloid leukaemia. The assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Antibodies are proteins in the body that target and link specific structures on the surface of foreign bodies, such as bacteria or cancer cells. CD33 is a protein found on the surface of acute myeloid leukaemia cells. Gemtuzumab ozogamicin is an antibody chemically linked to a specific compound that recognises and binds specifically to the CD33 protein. Following the binding, the cancer cells itself transforms the compound linked to the antibody into a type of toxic substance, which might lead to the destruction of the cancer cell.

The effects of gemtuzumab ozogamicin 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.

Gemtuzumab ozogamicin was being marketed in the United States for the treatment of patients with CD33-positive acute myeloid leukaemia in first relapse who are 60 years of age or older and who are not considered candidates or cytotoxic chemotherapy, at the time of submission.

Orphan designation of gemtuzumab ozogamicin had been granted in the United States for the same indication and in Japan for patients with relapsed or refractory acute myelogenous (myeloid) leukaemia.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 September 2000 recommending the granting of this designation.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment.

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.