EU/3/16/1624

Chronic lymphocytic leukaemia (CLL) is cancer of a type of white blood cell called B lymphocytes or B cells. In this disease, the B cells multiply too quickly and live for too long, so that there are too many of them circulating in the blood. The cancerous B cells look normal, but they are not fully developed and do not work properly. Over time, the cancer cells replace the normal white cells, red cells and platelets in the bone marrow (the spongy tissue inside the large bones in the body, where blood cells are produced).

The disease known as 'small lymphocytic lymphoma' (SLL) is the same disease as CLL. The name SLL is used when the cancer cells are located mainly in the lymph nodes.

CLL/SLL is the most common type of leukaemia and mainly affects older people. It is rare in people under the age of 40 years. CLL/SLL is a long-term debilitating and life-threatening disease because some patients develop severe infections.

At the time of designation, CLL/SLL affected approximately 4.5 in 10,000 people in the European Union (EU). This was equivalent to a total of around 231,000 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 513,700,000 (Eurostat 2016).

Treatment for CLL/SLL 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. Patients whose CLL/SLL is not causing any symptoms or is getting worse only very slowly may not need treatment. Treatment for CLL/SLL is started only if symptoms become troublesome. At the time of designation, the main treatment for CLL/SLL was chemotherapy (medicines to treat cancer).

The sponsor has provided sufficient information to show that acalabrutinib might be of significant benefit for patients with CLL/SLL because early studies showed that this medicine improved survival. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Acalabrutinib is expected to work by blocking an enzyme called Bruton's tyrosine kinase (Btk), which is found in B cells. Btk promotes growth and survival of B cells. By blocking Btk, acalabrutinib is expected to slow down the build-up of cancerous B cells in CLL/SLL, thereby delaying or stopping the progression of the disease.

The medicine is expected to be taken by mouth.

The effects of acalabrutinib have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with acalabrutinib in patients with CLL/SLL were ongoing.

At the time of submission, acalabrutinib was not authorised anywhere in the EU for CLL/SLL. Orphan designation of acalabrutinib had been granted in the United States for chronic lymphocytic leukaemia.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 18 February 2016 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.