EU/3/10/762: Orphan designation for the treatment of chronic myeloid leukaemia

Chronic myeloid leukaemia (CML) is a cancer of the white blood cells (cells that fight against infections). In patients with CML, the bone marrow (the spongy tissue inside the large bones) produces large numbers of abnormal, immature white blood cells called 'blasts', so there are too many of them circulating in the blood. These blast cells are not fully developed and do not work properly. Over a period of time, they replace the normal white blood cells, red blood cells and platelets in the bone marrow.

CML is most common in adults and older people, but children may also be affected. The disease usually develops very slowly, which is why it is called 'chronic'. However, when it progresses, CML is a severe and life-threatening disease that is associated with poor overall survival.

At the time of designation, CML affected approximately 1.6 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 81,000 people, and is below the threshold 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 506,300,000 (Eurostat 2010).

Treatment for CML 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 CML were chemotherapy (medicines to treat cancer) and bone-marrow transplantation (a complex procedure where the bone marrow of the patient is destroyed and replaced with healthy bone marrow from a matched donor).

The sponsor has provided sufficient information to show that bosutinib might be of significant benefit for patients with CML because early studies indicate that it might improve the treatment of patients who do not respond to existing treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Bosutinib is expected to work by blocking two types of enzymes called Src and Abl tyrosine kinases. These enzymes can be found in some receptors on the surface of leukaemia cells, including the receptors that are involved in stimulating the cells to divide uncontrollably. By blocking these enzymes, bosutinib is expected to control the spread of leukaemia cells.

The effects of bosutinib have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with bosutinib in patients with CML were ongoing.

At the time of submission, bosutinib was not authorised anywhere in the EU for CML. Orphan designation of bosutinib had 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 6 May 2010 recommending the granting of this designation.

Update: Bosutinib (Bosulif) has been authorised in the EU since 27 March 2013 for for the treatment of adult patients with chronic-phase, accelerated-phase and blast-phase Philadelphia-chromosome-positive chronic myelogenous leukaemia previously treated with one or more tyrosine-kinase inhibitors and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options.

• 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.